185 results on '"Ecgonine"'
Search Results
2. Optimization and validation of simultaneous analyses of ecgonine, cocaine, and seven metabolites in human urine by gas chromatography–mass spectrometry using a one‐step solid‐phase extraction.
- Author
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Fernández, Nicolás, Cabanillas, Laura Marina, Olivera, Nancy Mónica, and Quiroga, Patricia Noemí
- Abstract
The presence of ecgonine in urine has been proposed as an appropriate marker of cocaine use. Only a few methods have been published for their determination along with cocaine and the rest of its metabolites. Due to their high polarity and consequent solubility in water, these have low recoveries, which is why it is necessary to increase the sensitivity, by the formation of hydrochloric salts or multiderivatization of the analytes or by performing two solid‐phase extractions (SPEs), considerably increasing the time and cost of the analysis. This work describes a fast and fully validated procedure for the simultaneous detection and quantification of ecgonine, ecgonine‐methyl‐ester, benzoylecgonine, nor‐benzoylecgonine, m‐hydroxybenzoylecgonine, cocaethylene, cocaine, norcocaine, and norcocaethylene in human urine (500 μL) using one SPE and simple derivatization. Separation and quantification were achieved by gas chromatography–electron ionization–mass spectrometry (GC–EI–MS) in selected‐ion monitoring mode. Quantification was performed by the addition of deuterated analogs as internal standards. Calibration curves were linear in the adopted ranges, with determination coefficients higher than 0.99. The lower limits of quantification ranged from 2.5 to 10 ng/mL. The intra‐ and inter‐day precision, calculated in terms of relative standard deviation, were 1.2%–14.9% and 1.8%–17.9%, respectively. The accuracy, in terms of relative error, was within a ± 16.4% interval. Extraction efficiency ranged from 84% to 103%. Compared with existing methods, the procedure described herein is fast, since only one SPE is required, and cost‐effective. In addition, this method provides a high recovery for ecgonine, resulting in a better alternative to the previously published methods. Development, optimization, and validation of a one‐step solid‐phase‐extraction (SPE) method with a simple derivatization coupled to gas chromatography–mass spectrometry (GC–MS) to identify and quantify ecgonine, cocaine, and seven other metabolites in human urine samples. This is the first report on the use of one cartridge of SPE, with high recoveries and better limits for quantification of COC and metabolites. The procedure is considered a better alternative to the previously published methods. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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3. Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase
- Author
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Weixuan Yao, Jiye Wang, Kang Yang, Junseng Tong, Yanan Wu, Yun Zhang, Xiabin Chen, Qiang Li, Xingyu Deng, Tian Xie, Shurong Hou, and Jianzhuang Yao
- Subjects
chemistry.chemical_classification ,Models, Molecular ,Chromatography ,Cocaine Esterase ,Molecular Structure ,Hydrolases ,Metabolite ,General Chemistry ,General Medicine ,Catalysis ,chemistry.chemical_compound ,Enzyme ,chemistry ,Cocaine ,Toxicity ,Hydrolase ,Benzoylecgonine ,Ecgonine ,Benzoic acid - Abstract
Benzoylecgonine (BZE) is the major toxic metabolite of cocaine and is responsible for the long-term cocaine-induced toxicity owing to its long residence time in humans. BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo, a single dose of BZEase2 (1 mg kg-1 , IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined.
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- 2021
4. Drug laws and the 'derivative' problem.
- Author
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King, Leslie A., Ujváry, István, and Brandt, Simon D.
- Abstract
The concept of a 'derivative' is used widely in chemistry, where its precise meaning depends on the circumstances. However, numerous examples of derivative also occur in domestic drugs legislation, some of which stem from the 1961 United Nations Single Convention on Narcotic Drugs. There is a commonly held view that only 'first-order' derivatives should be considered: substances that can be created from a parent structure in a single chemical reaction. In other words, 'derivatives of derivatives' are excluded. However, some substances related to ecgonine (e.g. 2-carbomethoxytropinone) are clearly convertible to cocaine, even though this may require more than one reaction step. It follows that 2-carbomethoxytropinone is a controlled drug, a situation that most chemists would regard as perverse. A more extreme example of the complexity of 'derivative' is shown by the conversion of thebaine to buprenorphine. Even though this requires six or more stages, the US Drug Enforcement Administration successfully argued in a 1986 case that for the purposes of the Controlled Substances Act, the number of steps required was irrelevant; buprenorphine was a derivative of thebaine. Because the term derivative is rarely defined in statutes, the legal status of some substances, such as 2-bromo-LSD, is uncertain. Although a number of definitions of derivative can be found in the chemical literature, no single definition is adequate to describe all situations where it occurs in legislation. Unless qualified, it is suggested that the term derivative should be avoided in any future legislation. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2014
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5. Stability of cocaine and its metabolites in municipal wastewater - the case for using metabolite consolidation to monitor cocaine utilization.
- Author
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Bisceglia, Kevin and Lippa, Katrice
- Subjects
COCAINE ,METABOLITES ,SEWAGE ,HYDROLYSIS ,BIOMOLECULES - Abstract
Transformations of cocaine and eleven of its metabolites were investigated in untreated municipal sewage at pH ≈ 7 and 9, 23, and 31 °C. Results indicated that hydrolysis-possibly bacterially mediated-was the principal transformation pathway. Residues possessing alkyl esters were particularly susceptible to hydrolysis, with pseudo-first-order rate constants varying from 0.54 to 1.7 day at 23 °C. Metabolites lacking esters or possessing only a benzoyl ester appeared stable. Residues lacking alkyl esters did accumulate through hydrolysis of precursors, however. As noted previously, this may positively bias cocaine utilization estimates based on benzoylecgonine alone. Reported variability in metabolic excretion was used in conjunction with transformation data to evaluate different approaches for estimating cocaine loading. Results indicate that estimates derived from measurands that capture all major cocaine metabolites, such as COC (the sum of all measurable metabolites) and EC (the sum of all metabolites that can be hydrolyzed to ecgonine), may reduce uncertainty arising from variability in metabolite transformation and excretion, possibly to ≈ 10 % RSD. This is more than a two-fold reduction relative to estimates derived from benzoylecgonine (>26 % RSD), and roughly equivalent to reported uncertainties from sources that are not metabolite-specific (e.g., sampling frequency, flow variability). They and other composite measurands merit consideration from the sewage epidemiology community, beginning with efforts to evaluate the stability of the total cocaine load under realistic sewer conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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6. A Validated and Applicable Direct Injection LC/MS/MS Method of Fourteen Drugs of Abuse in Urine Samples to Avoid the False Positive/Negative Results of Immunoassay Techniques in Forensic Cases
- Author
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Abdulaziz Al-Sulaiti, M. I. Ahmad, Yasser Abdelqader, Gaffar Hag, Abdelrahman Fikry, and Tarek Mahdy
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Drugs of abuse ,Chromatography ,medicine.diagnostic_test ,LC/MS/MS ,business.industry ,Urine ,Methamphetamine ,Benzoylecgonine ,chemistry.chemical_compound ,Amphetamine ,chemistry ,Immunoassay ,Lc ms ms ,medicine ,Ecgonine ,business ,medicine.drug - Abstract
Many false positive and false negative results have been detected in immunoassay analyses of drugs of abuse in urine samples. A method of direct injection of diluted urine into LC/MS/MS was developed and validated for detection and quantitation of Amphetamine, Methamphetamine, MDMA, MDA, Benzoylecgonine, Ecgonine, Norpseudoephedrine, Ephedrine, Tapentadol, Tramadol, O-desmethyltramadol, Tapentadol, Pregabline, Gabapentine and Methadone to avoid the false positive and false negative results in urine samples. Linearity of Amphetamine, Methamphetamine MDMA, MDA, Benzoylecgonine, Ecgonine, Norpseudoephedrine and Ephedrine was (60-2400ng/mL), for Tapentadol, Tramadol, O-desmethyltramadol, and Methadone was (50-1600 ng/mL), and for Pregabline and Gabapentine was (100-4000ng/mL) and r2 ˃ 0.992 for all analysts. A 440 urine samples have been analyzed using both immunoassay technique and LC/MS/MS by direct injection method giving a good comparison to illustrate how this method was specific, accurate, precise, and applicable for forensic urine samples
- Published
- 2020
7. Determination of ecgonine and seven other cocaine metabolites in human urine and whole blood by ultra-high-pressure liquid chromatography–quadrupole time-of-flight mass spectrometry.
- Author
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Xiong, Lingjuan, Wang, Rong, Liang, Chen, Cao, Fangqi, Rao, Yulan, Wang, Xin, Zeng, Libo, Ni, Chunfang, Ye, Haiying, and Zhang, Yurong
- Subjects
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COCAINE , *TANDEM mass spectrometry , *METABOLITES , *URINALYSIS , *HIGH performance liquid chromatography , *BLOOD - Abstract
Ecgonine is suggested to be a promising marker of cocaine (COC) ingestion. A combined mass spectrometry (MS) and tandem MS (MS/MS) method was developed to simultaneously determine ecgonine and seven other metabolites of cocaine in human urine and whole blood with ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The compounds were extracted from as little as 100 μL of sample by solid-phase extraction with a 96-well μElution solid-phase extraction plate. The protonated molecules or fragment ions at accurate mass acquired in MS mode were used to quantify specific analytes, following by dedicated MS/MS identification. The assay was linear in the range from 5 to 50-100 ng/mL for urine samples, except for ecgonine methyl ester (10-200 ng/mL) and ecgonine (40-400 ng/mL), and was linear from 1-2 to 50 ng/mL for whole blood samples, except for ecgonine methyl ester (20-1,000 ng/mL) and ecgonine (40-2,000 ng/mL). The correlation coefficients were all greater than 0.99. The limits of detection ranged from 0.2 to 16 ng/mL, and the lower limits of quantification ranged from 1 to 40 ng/mL. The repeatability and intermediate precision were 18.1 % or less. The accuracy was in the range from 80.0 to 122.9 %, process efficiencies were in the range from 8.6 to 177.4 %, matrix effects were in the range from 28.7 to 171.0 %, and extraction recoveries were in the range from 41.0 to 114.3 %, except for ecgonine (12.8 % and 9.3 % at low and high concentrations, respectively). This method was highly sensitive in comparison with previously published methods. The validated method was successfully applied to the analysis of real samples derived from forensic cases, and the results verified that, on the basis of data from four positive samples, ecgonine is a promising marker of cocaine ingestion. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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8. Screening of drugs and homeopathic products from Atropa belladonna seed extracts: Tropane alkaloids determination and untargeted analysis
- Author
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Roberto Romero-González, Francisco J. Egea-González, Jesús Marín-Sáez, and Antonia Garrido Frenich
- Subjects
Atropine ,Modern medicine ,Scopolamine ,Pharmaceutical Science ,Poison control ,01 natural sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Apoatropine ,Alkaloids ,Tandem Mass Spectrometry ,Atropa belladonna ,Environmental Chemistry ,Chromatography, High Pressure Liquid ,Spectroscopy ,Tropine ,Traditional medicine ,Plant Extracts ,010405 organic chemistry ,010401 analytical chemistry ,Tropinone ,Tropane ,0104 chemical sciences ,chemistry ,Seeds ,Ecgonine ,Tropanes - Abstract
Homeopathic products are still a controversial issue in modern medicine, understood as complementary or alternative medicine (CAM). In this particular case, homeopathic products prepared from Atropa belladonna extracts may present specific problems due to the effects derived from its components. This article applies a simple, rapid, reliable method to the analysis of different homeopathic products obtained from Atropa belladonna; drugs containing high concentration of plant extracts; and Atropa belladonna seeds. The method was based on a simple solid-phase preconcentration method followed by ultra-high pressure liquid chromatography (UHPLC) coupled to high resolution mass spectrometry using Exactive-Orbitrap as an analyser. An in-house database was set and atropine and scopolamine were the compounds detected at highest concentrations in homeopathic products from Atropa belladonna extracts (4.57 and 2.56 μg/kg, respectively), in Belladonna ointment (4007 and 1139 μg/kg, respectively) and Belladonna seeds (338 and 32.1 mg/kg, respectively). Other tropane alkaloids such as tropine, apoatropine, aposcopolamine, tropinone, homatropine, and anisodamine were detected at lower concentrations (0.04-1.36 μg/kg). When untargeted analysis was performed, other tropane alkaloids were identified in the tested samples, such as ecgonine (0.003 μg/kg), benzoylecgonine (0.56 μg/kg), calystegines A (19.6 μg/kg), B (33.1 μg/kg), and C (1.01 μg/kg). Finally other compounds present in the homeopathic products, such as sugars (fructose, glucose, and lactose) or amino acids (valine, ornithine, leucine, and phenylalanine), were identified.
- Published
- 2018
9. Cocaine binding to the Fab fragment of a humanized anti-cocaine mAb quantitated by dye absorption and fluorescence spectroscopy
- Author
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Terence L. Kirley and Andrew B. Norman
- Subjects
Immunology ,Pyridinium Compounds ,Antibodies, Monoclonal, Humanized ,Ligands ,Article ,Fluorescence spectroscopy ,Absorbance ,Cocaine-Related Disorders ,Immunoglobulin Fab Fragments ,chemistry.chemical_compound ,Cocaine ,Antibody Specificity ,Predictive Value of Tests ,Humans ,Immunology and Allergy ,Binding site ,Fluorescent Dyes ,Cocaine binding ,Chromatography ,Chemistry ,Fluorescence ,Norcocaine ,Substance Abuse Detection ,Spectrometry, Fluorescence ,Titration ,Ecgonine ,Protein Binding - Abstract
In this work, we establish that cocaine binding to the Fab fragment of a recombinant humanized anti-cocaine mAb (h2E2) can be directly and easily quantitated using simple and inexpensive absorption and fluorescence measurements, employing dyes typically used for differential scanning fluorimetry, DASPMI and SYPRO Orange. For concentrated samples of the Fab fragment, absorbance spectroscopy employing these dyes reveals the number of cocaine sites present, using either DASPMI (by measuring the increase in dye absorbance) or SYPRO Orange (by measuring the change in dye maximal absorbance wavelength). Interestingly, we observed that cocaine binding to the Fab fragment had a much different effect on the SYPRO Orange dye absorbance than previously reported for the intact h2E2 mAb, resulting in a large decrease in the total dye absorbance for the Fab fragment, in contrast to previous results with the intact h2E2 mAb. For dilute samples of Fab fragment, a dye fluorescence emission spectroscopy assay was developed to quantitate the number of cocaine (and other high affinity cocaine metabolites) binding sites via the ligand-induced decrease in fluorescence emission of both of these extrinsic dyes. The difference in the cocaine titrations for the high affinity (Kd < 30 nM) ligands, cocaine, cocaethylene and benzoyl ecgonine and the low affinity (Kd > 30 μM) ligands, norcocaine, ecgonine methyl ester, and ecgonine were obvious using this assay. These simple, direct, and inexpensive techniques should prove useful for evaluation of other small molecule antigen binding Fab fragments, enabling quantitation and rapid biochemical assessments necessary for determining Fab fragment suitability for in vivo uses and other assays and experiments.
- Published
- 2021
10. Optimization of a rapid sample pretreatment for the quantification of COCAINE and its main metabolites in hair through a new and validated GC-MS/MS method
- Author
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Giulio Mannocchi, Giovanna Ricci, Ascanio Sirignano, Raffaele Giorgetti, Nunzia La Maida, and Francesco Paolo Busardò
- Subjects
Detection limit ,Chromatography ,Clinical Biochemistry ,Selected reaction monitoring ,Reproducibility of Results ,Pharmaceutical Science ,Mass spectrometry ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,Norcocaine ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,chemistry ,Tandem Mass Spectrometry ,Calibration ,Drug Discovery ,Benzoylecgonine ,medicine ,Gas chromatography–mass spectrometry ,Ecgonine ,Spectroscopy ,Hair ,medicine.drug - Abstract
We developed and validated a new rapid and sensitive gas chromatography-tandem mass spectrometry method for the determination of cocaine and its metabolites benzoylecgonine, norcocaine, ecgonine methyl esther and cocaethylene in hair of consumers. Hair samples were firstly decontaminated with three subsequent dichloromethane washes, then incubated for one hour with M3® buffer to promote analytes solubilization and stabilization and finally solid phase extracted. All extracts were derivatized and injected into GC–MS/MS with electron impact ionization. Multiple Reaction Monitoring was used for the acquisition of characteristic analytes ion transitions reaching a high sensitivity 0.01 ng/mg COC and metabolites limit of quantification. The method was linear in the COC and metabolites calibration ranges (LLOQ-10 ng/mg and LLOQ-1 ng/mg, respectively). Intra-assay and inter-assay precision were always lower than 15 %, accuracy never exceeded ± 6.6 %. The main advantages of the presented method are the fast, simple and innovative pretreatment procedure together with the instrumental sensitivity that allowed to measure also less concentrated metabolites.
- Published
- 2021
11. A hydrolysis procedure for the analysis of total cocaine residues in wastewater.
- Author
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Bisceglia, Kevin, Roberts, A., and Lippa, Katrice
- Subjects
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SOLID phase extraction , *TANDEM mass spectrometry , *WASTEWATER treatment , *HYDROPHILIC interactions , *COCAINE - Abstract
We report a sample pretreatment approach for the analysis of total cocaine residues in wastewater that eliminates the need for two key assumptions often made in estimating cocaine utilization from measurement of its benzoylecgonine metabolite: that benzoylecgonine is neither degraded nor generated during transport in a sewer system, and that it is excreted as a constant fraction of cocaine ingested. By adding NaOH and incubating samples at 55 °C, cocaine and its principal metabolites are efficiently hydrolyzed into ecgonine, anhydroecgonine, and norecgonine. Ecgonine, estimated to represent between 37% and 90% (on a molar basis) of cocaine residues, can be directly determined (without preconcentration via solid-phase extraction (SPE)) by reversed-phase (RP) or hydrophilic interaction liquid chromatography-tandem mass spectrometry (LC/MS/MS). If samples are subjected to SPE, anhydroecgonine can also be determined; this metabolite (and its precursors) represents ≈7% of urinary cocaine residues (based on spot collections from living individuals). Although a reference standard for norecgonine is not commercially available, such nortropanes are also a minor fraction (up to 2%) of urinary cocaine residues. The stability of two human markers (cotinine and creatinine) to the hydrolysis procedure was also investigated. Results obtained by applying the hydrolysis approach for the analysis of total cocaine in an untreated municipal wastewater sample (obtained from Baltimore, MD) were generally in excellent agreement with those obtained from split samples analyzed using a more comprehensive solid-phase extraction RPLC/MS/MS method as described in our previous work. In particular, total tropane-based cocaine residues were found to be hydrolyzed to ecgonine with 98-99% efficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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12. Gender differences in cocaine pharmacokinetics in CF-1 mice
- Author
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Visalli, Thomas, Turkall, Rita, and Abdel-Rahman, Mohamed S.
- Subjects
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HEPATOTOXICOLOGY , *LOCAL anesthetics , *ORGANS (Anatomy) , *TISSUES - Abstract
Abstract: Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed. Male and female CF-1 mice were orally administered 20mg/kg cocaine hydrochloride once daily for 7 days. Blood samples were withdrawn at various time points post-injection and analyzed for cocaine and its metabolites benzoylecgonine (BE), norcocaine, ecgonine methyl ester (EME), and ecgonine (E). In addition, tissue concentrations of cocaine and its metabolites were determined in liver, heart, brain, and kidney tissue. The results demonstrated that the plasma elimination half-life of cocaine is nearly three times longer in males versus females. Non-hepatotoxic hydrolysis metabolites BE, EME, and E were higher in female tissues while norcocaine was detected in tissues of male animals only. This study revealed that differences in cocaine pharmacokinetics and the resultant differences in the biodisposition of cocaine and its metabolites in tissues contribute to the mechanism of gender difference seen in cocaine hepatotoxicity. [Copyright &y& Elsevier]
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- 2005
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13. Studying electrode mechanism and analytical determination of cocaine and its metabolites at the mercury electrode using square-wave voltammetry
- Author
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Pavlova, Valentina, Mirčeski, Valentin, Komorsky-Lovrić, Šebojka, Petrovska-Jovanović, Simka, and Mitrevski, Blagoj
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- *
COCAINE , *METABOLITES , *MERCURY , *ELECTRODES - Abstract
Electrochemical properties of cocaine and its metabolites such as benzoylecgonine (BE), ecgonine (ECG), and ecgonine methyl ester (EME) have been studied by means of square-wave voltammetry (SWV) at a hanging mercury drop electrode. In a phosphate buffer at pH 7 cocaine gives rise to a single voltammetric peak at about -1.490 V versus AgCl (3 mol/l KCl). At higher pH, BE is spontaneously formed, as a first hydrolysis product of cocaine. BE can further hydrolyse to ecgonine that is electrochemically inactive at the mercury electrode. Ecgonine methyl ester, an another hydrolysis product of cocaine, is electrochemically inactive at the mercury electrode, too. BE undergoes reduction owing to its ester group, giving rise to a voltammetric peak within the potential interval from -1.010 to -1.200 V, depending on the concentration of BE. Thus, at pH 8.5, cocaine solution gives rise to two SW peaks due to the reduction of unhydrolysed cocaine and BE. The reduction of BE undergoes through a complex electrode mechanism coupled by adsorption and two types of following chemical reactions. The reduction electrode product of BE undergoes (i) dimerisation and then (ii) protonation leading to final products, most probably ecgonine and benzaldehyde. The rate of the later chemical reaction is controlled by the proton concentration in the electrolyte solution. Comparing the voltammetric properties of cocaine to that of BE and methyl ester ecgonine, it has been concluded that the electrochemical activity of cocaine originates from the reduction of the same ester group as in the case of BE. The main difference between cocaine and BE is manifested in their tendency for adsorption on the mercury electrode surface. BE adsorbs stronger than cocaine, and hence an adsorptive stripping voltammetric method for determination of cocaine was developed on the basis of BE reduction. [Copyright &y& Elsevier]
- Published
- 2004
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14. Alkaloid Content in Two Erythroxylum Taxa During Juvenile Growth and Development.
- Author
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Johnson, Emanuel L.
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ERYTHROXYLUM ,ALKALOIDS ,PLANT metabolites ,PLANT growth ,PLANT embryology ,COCAINE - Abstract
Erythroxylum coca var. coca Lam. and Erythroxylum novogranatense var. novogranatense (Morris) Hieron (E.n. var. novogranatense) were grown in a controlled environment for 52 weeks to monitor the content of hygrine, tropinone, tropacocaine, methyl ecgonine, cocaine and cis- and trans-cinnamoylcocaine in seeds, plant parts, and organs during juvenile growth. Embryos and endosperms of var. coca contained cocaine while only embryos of var. novogranatense contained cocaine. Tropacocaine was present in hypocotyls, stems and roots of var. novogranatense, but not in var. coca. Trans-cinnamoylcocaine was the most abundant alkaloid in cotyledons (12 weeks after seeding) and leaves (24 weeks after seeding) in both var. coca and var. novogranatense. After 52 weeks of seeding growth, cocaine was the preeminent alkaloid in leaves of both taxons with a cocaine content of 0.66 percent in var. coca and 1.04 percent in var. [ABSTRACT FROM PUBLISHER]
- Published
- 2002
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15. Applicability of ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry for cocaine profiling
- Author
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Zhendong Hua, Xin Meng, and Cuimei Liu
- Subjects
Chromatography ,010401 analytical chemistry ,Analytical chemistry ,Pharmaceutical Science ,Drug profiling ,Mass spectrometry ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Norcocaine ,03 medical and health sciences ,chemistry.chemical_compound ,Tropacocaine ,0302 clinical medicine ,chemistry ,Benzoylecgonine ,Environmental Chemistry ,Profiling (information science) ,Sample preparation ,030216 legal & forensic medicine ,Ecgonine ,Spectroscopy - Abstract
For the first time in China, the chemical profiling of cocaine specimens was performed at the National Narcotics Laboratory. An ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) method was developed and validated for simultaneous analysis of 14 cocaine alkaloids and 5 main adulterants. Among them, ecgonine methyl ester, ecgonine, benzoylecgonine, and norcocaine were identified by comparing with the standard materials; tropacocaine, 3,4,5-trimethoxycocaine, cis-/trans-cinnamoylcocaine were tentatively identified based on the exact masses of protonated molecules and product ions; six unidentified alkaloids of 182/1.47, 316/9.54, 659/9.85, 316/9.87, 420/10.34, and 420/10.85 were marked with 'extracted mass/retention time' for convenience. Minimum sample preparation and analysis time were required, which was suitable for routine analysis. Based on the semi-quantitative data set of 14 alkaloid impurities in 131 linked/unlinked cocaine samples, 50 combinations of pretreatment methods and distance/correlation measurements were tested for their potential discrimination power for cocaine profiling, and Logarithm/Pearson exhibited the best result. After hierarchical cluster analysis (HCA), 183 cocaine samples collected from 2011 to 2015 were classified into 7 major groups. Moreover, 37 groups of linked samples were found within and between provinces, which provide intelligence for the case connection and revealing of the distribution networks. Our results highlighted the practical utilities of drug profiling, especially to support the investigation through operational intelligence and to improve the knowledge related to the drug trafficking through strategic intelligence. Copyright © 2016 John Wiley & Sons, Ltd.
- Published
- 2016
16. Method Development and Validation for Determination of Cocaine, its Main Metabolites and Pyrolytic Products by HPLC–UV–CAD
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Pedro Eduardo Fröehlich, Andrea Garcia Pereira, Pamela C.L. Ferreira, Felipe Bianchini D'Avila, Marcelo Gatteli Holler, and Renata Pereira Limberguer
- Subjects
Chromatography ,Hydrophilic interaction chromatography ,010401 analytical chemistry ,Organic Chemistry ,Clinical Biochemistry ,02 engineering and technology ,021001 nanoscience & nanotechnology ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,High-performance liquid chromatography ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,medicine ,Benzoylecgonine ,Pyrolytic carbon ,0210 nano-technology ,Ecgonine ,Acetonitrile ,Ammonium acetate ,Ultraviolet - Abstract
A method was developed using hydrophilic interaction liquid chromatography (HILIC), a versatile mode of liquid chromatography, to determine cocaine, its main degradation products, benzoylecgonine and ecgonine, main pyrolytic products, anhydroecgonine and anhydroecgonine methyl ester, to be used as standards, and a frequent contaminant, levamisole. Detection of all compounds was achieved using two detectors connected in series: charged aerosol detector (CAD) and ultraviolet detector (UV). No method was found in the literature using HILIC coupled to CAD and UV to determine these compounds. The method was carried out with a Phenomenex Kinetex HILIC (150 mm × 4.6 mm ID; 2,6 µm) column with mobile-phase acetonitrile: 10 mM ammonium acetate pH 6.3 (75:25 v/v) with flow rate 0.8 mL min−1 and oven temperature set at 30 °C. CAD detection was performed using a nitrogen pressure of 35 psi, range of 100 pA and the UV detection at 200 nm. Validation parameters such as selectivity, linearity, precision and accuracy were evaluated. Methods were successfully validated to detect and quantify all related substances.
- Published
- 2015
17. Optimization and validation of simultaneous analyses of ecgonine, cocaine, and seven metabolites in human urine by gas chromatography-mass spectrometry using a one-step solid-phase extraction
- Author
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Nicolás Fernández, Nancy Mónica Olivera, Laura Marina Cabanillas, and Patricia N. Quiroga
- Subjects
Analyte ,Pharmaceutical Science ,01 natural sciences ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cocaethylene ,Cocaine ,Limit of Detection ,medicine ,Environmental Chemistry ,Humans ,030216 legal & forensic medicine ,Solid phase extraction ,Derivatization ,Spectroscopy ,Chromatography ,010401 analytical chemistry ,Solid Phase Extraction ,0104 chemical sciences ,Norcocaine ,Data Accuracy ,Substance Abuse Detection ,chemistry ,Benzoylecgonine ,Gas chromatography–mass spectrometry ,Ecgonine ,medicine.drug - Abstract
The presence of ecgonine in urine has been proposed as an appropriate marker of cocaine use. Only a few methods have been published for their determination along with cocaine and the rest of its metabolites. Due to their high polarity and consequent solubility in water, these have low recoveries, which is why it is necessary to increase the sensitivity, by the formation of hydrochloric salts or multiderivatization of the analytes or by performing two solid-phase extractions (SPEs), considerably increasing the time and cost of the analysis. This work describes a fast and fully validated procedure for the simultaneous detection and quantification of ecgonine, ecgonine-methyl-ester, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, cocaethylene, cocaine, norcocaine, and norcocaethylene in human urine (500 μL) using one SPE and simple derivatization. Separation and quantification were achieved by gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) in selected-ion monitoring mode. Quantification was performed by the addition of deuterated analogs as internal standards. Calibration curves were linear in the adopted ranges, with determination coefficients higher than 0.99. The lower limits of quantification ranged from 2.5 to 10 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 1.2%-14.9% and 1.8%-17.9%, respectively. The accuracy, in terms of relative error, was within a ± 16.4% interval. Extraction efficiency ranged from 84% to 103%. Compared with existing methods, the procedure described herein is fast, since only one SPE is required, and cost-effective. In addition, this method provides a high recovery for ecgonine, resulting in a better alternative to the previously published methods.
- Published
- 2018
18. An exploratory study of information sources and key findings on UK cocaine-related deaths
- Author
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Fabrizio Schifano, Christine Goodair, Hugh Claridge, and John Corkery
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,media_common.quotation_subject ,Ecgonine methyl ester ,Exploratory research ,Autopsy ,03 medical and health sciences ,chemistry.chemical_compound ,Cocaine-Related Disorders ,Young Adult ,0302 clinical medicine ,Cocaethylene ,Cocaine ,Cause of Death ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Registries ,media_common ,Cause of death ,Aged ,Pharmacology ,Aged, 80 and over ,business.industry ,Addiction ,Age Factors ,Middle Aged ,United Kingdom ,Substance Abuse Detection ,Psychiatry and Mental health ,chemistry ,Emergency medicine ,Benzoylecgonine ,Female ,Drug Overdose ,business ,Ecgonine ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Cocaine-related deaths have increased since the early 1990s in Europe, including the UK. Being multi-factorial, they are difficult to define, detect and record. The European Monitoring Centre for Drugs and Drug Addiction commissioned research to: describe trends reported to Special Mortality Registries and General Mortality Registers; provide demographic and drug-use characteristic information of cases; and establish how deaths are identified and classified. A questionnaire was developed and piloted amongst all European Monitoring Centre for Drugs and Drug Addiction Focal Point experts/Special Mortality Registries: 19 (63%) responded; nine countries provided aggregated data. UK General Mortality Registers use cause of death and toxicology to identify cocaine-related deaths. Categorisation is based on International Classification of Diseases codes. Special Mortality Registries use toxicology, autopsy, evidence and cause of death. The cocaine metabolites commonly screened for are: benzoylecgonine, ecgonine methyl ester, cocaethylene and ecgonine. The 2000s saw a generally accelerating upward trend in cases, followed by a decline in 2009. The UK recorded 2700–2900 deaths during 1998–2012. UK Special Mortality Registry data (2005–2009) indicate: 25–44 year-olds account for 74% of deaths; mean age=34 (range 15–81) years; 84% male. Cocaine overdoses account for two-thirds of cases; cocaine alone being mentioned/implicated in 23% in the UK. Opioids are involved in most (58%) cocaine overdose cases.
- Published
- 2017
19. Drug-Drug Interactions in Cocaine-users and their Clinical Implications
- Author
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Antonio Siniscalchi, Luca Gallelli, Paolo Seminara, Santo Gratteri, Giovambattista De Sarro, Maria Cristina Caroleo, Sabrina Sirico, and Erika Cione
- Subjects
0106 biological sciences ,0301 basic medicine ,Drug ,media_common.quotation_subject ,Adrenergic beta-Antagonists ,Bioinformatics ,Serotonergic ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Cocaine-Related Disorders ,Cocaine ,010608 biotechnology ,medicine ,Humans ,Drug Interactions ,media_common ,business.industry ,medicine.disease ,Norcocaine ,Psychiatry and Mental health ,030104 developmental biology ,chemistry ,Pharmacodynamics ,Benzoylecgonine ,Cytochrome P-450 CYP3A Inhibitors ,Nefazodone ,business ,Ecgonine ,Adverse drug reaction ,medicine.drug - Abstract
Background Drug-Drug Interactions (DDIs) represent a common problem in clinical practice during drug treatments. DDIs can both induce the development of adverse drug reactions or reduce the clinical efficacy of each drug. Objectives The main objective of this review was to analyze the pharmacokinetic and pharmacodynamic DDIs in cocaine consumers, focusing the interest on their clinical implications. Methods The PubMed, Embase and Cochrane library databases were searched for articles published until January 10, 2017. Secondary search included articles cited in reference lists identified by the primary search. Papers were deemed eligible if they included any form of words: "adverse drug reaction", "drug interactions", "poly-therapy", "cocaine", "systemic diseases". Results In this review, the nodal points treated concern: i) cocaine biochemical metabolism described for both, inactive benzoylecgonine and ecgonine methyl esters and norcocaine active metabolites. We provided evidences of concepts deriving from rat/mice experimental studies speculating a translation approach to human in order to treat cocaine overdose. ii) Drug-drug interactions, which come out from clinical evidences as the case of CYP450 family enzyme inhibitors or inductors modulating cocaine toxicity. Particularly, we highlighted the lack of knowledge concerning cocaine and CYP3A4 inhibitors (such as ketoconazole, nefazodone, erythromycin, and clarithromycin). We recorded the worst association of cocaine and beta-blockers by direct and indirect action, particularly at postsynaptic levels on dopamine and norepinephrine reuptake, sympathetic activation and increase of heart rate, blood pressure and cardiovascular toxicity. Cocaine also induces increase in serotonin synaptic activity leading to the development of a serotoninergic syndrome when used with drugs that affect serotonin pathway. Genetic (i.e. glutathione peroxidase-1 deficiency) and epigenetic factors (i.e. microRNAs) may be involved in drug-drug interactions in cocaine-users are also being introduced. Conclusion DDIs represent an important potential complication in cocaine users in clinical setting. The knowledge of DDIs can also be used to select treatments for patients, thus optimizing clinical response and minimizing toxicity.
- Published
- 2017
20. Hydrogen peroxide reactions on cocaine in hair using imaging mass spectrometry
- Author
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Ingrid J. Bosman, Bryn Flinders, Eva Cuypers, Klaas J. Lusthof, Arian C. van Asten, Jan Tytgat, Ron M. A. Heeren, Imaging Mass Spectrometry (IMS), RS: M4I - Imaging Mass Spectrometry (IMS), and Analytical Chemistry and Forensic Science (HIMS, FNWI)
- Subjects
Narcotics ,Ionization mass ,Mass spectrometry imaging ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Cocaine-Related Disorders ,Forensic Toxicology ,Imaging mass spectrometry ,Cocaine ,Humans ,Hydrogen peroxide ,Hair Bleaching Agents ,Chromatography ,integumentary system ,Hair analysis ,Forensic hair testing ,Substance Abuse Detection ,chemistry ,Environmental chemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Benzoylecgonine ,Cocaine use ,sense organs ,Ecgonine ,Law ,Hair - Abstract
Today, forensic hair analysis is considered to be a standard method for identifying chronic drug users since information about drug use stored and located in hair can cover several months to even years. When interpreting these results, one should be aware of all kind of pitfalls. External factors such as bleaching might influence the analytical result. Although the effect of hydrogen peroxide on cocaine in a solution was described before, it was never investigated whether the described reaction products (ecgonine methylester, benzoylecgonine, hydroxynorcocaine and dihydroxycocaine) are indeed found on contaminated or user hair. Since it is of great importance in forensic hair analysis to know whether cocaine and/or reaction products are detectable in hair after bleaching, matrix-assisted laser desorption/ ionization mass spectrometric imaging (MALDI-MSI) was used to study the effect of hydrogen peroxide treatment on incorporated cocaine in hairs. Cocaine oxidation products were identified in a solution based on MS/MS spectra and spatial distribution of these products in hair was explored using MALDI TOF-MS. All images were accomplished by spraying alpha-Cyano-4-hydroxycinnamic acid (CHCA) as a MALDI-matrix. Images revealed a loss of detectability of cocaine and its reaction products in hairs already after a short bleaching period. Since all compounds of interest are found in the hydrogen peroxide and wash solution, these findings indicate that all evidence of cocaine use might be lost after a hair bleaching treatment. Therefore, forensic toxicologists should take into consideration whether hair samples were bleached before making any conclusions from hair analysis results.
- Published
- 2014
21. Differentiating crack cocaine from regular cocaine in whole blood samples in drugs and driving cases
- Author
-
Albert A. Elian and Jeffery Hackett
- Subjects
Chromatography ,Formic acid ,Elution ,General Chemical Engineering ,Extraction (chemistry) ,General Engineering ,Hydrochloric acid ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaethylene ,chemistry ,Benzoylecgonine ,medicine ,Solid phase extraction ,Ecgonine ,medicine.drug - Abstract
In this study, the procedure for analyzing cocainic drugs and metabolites (anhydroecgnonine, anhydroecgnonine methyl ester, benzoylecgonine, cocaine, cocaethylene, ecgnonine ethyl ester, and ecgnonine methyl ester) in whole blood samples obtained from drugs and driving cases using a mixed mode solid phase extraction (SPE) C8/SCX cartridge (Clean Screen DAU206), is described. This extraction and analysis procedure allows forensic analysts to differentiate between drivers who have used “crack cocaine” against those using regular cocaine. Samples of whole blood (containing deuterated internal standards) were diluted with an aqueous phosphate buffer (pH 6). Each sample was applied to a conditioned SPE column. The filtrate was collected and adjusted to pH 2. The sorbent was rinsed with deionized (DI) water, aqueous hydrochloric acid and methanol. After drying, cocaine, cocathylene, benzoylecgnonine, and anhydroecgnonine methyl ester were eluted from the SPE column with 3 mL of an elution solvent consisting of methylene chloride–isopropanol–ammonium hydroxide. The original filtrate was applied to a second conditioned SPE column and washed with DI water, aqueous hydrochloric acid and methanol. After drying the SPE sorbent, anhydroecgnonine was eluted with methanol containing 4% ammonium hydroxide (3 mL). The eluates were combined and evaporated to dryness, and the residue was dissolved in the mobile phase for analysis by LC-MS/MS in positive multiple reaction monitoring mode (MRM). Chromatography was performed in gradient mode employing a C18 column and a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. The total run time for each analysis was within five minutes. The limits of quantitation/detection for this method were determined to be 0.5 ng mL−1 and 1.0 ng mL−1 respectively. The method was found to be linear from 1.0 ng mL−1 to 100.0 ng mL−1 (r2 > 0.995). The recoveries of the noted cocaine type drugs were found to be greater than 90%. This method was applied to twenty positive cocaine completed drugs and driving cases, it was found that anhydroecgnonine concentrations ranged from 0 ng mL−1 to 23 ng mL−1, anhydroecgonine methyl ester concentrations ranged from 0 ng mL−1 to 66 ng mL−1, while cocaine was found to range from 25 ng mL−1 to 250 ng mL−1, cocaethylene ranged from 0 ng mL−1 to 80 ng mL−1, benzoylecgnonine concentrations were found to be in the range 90 ng mL−1 to 790 ng mL−1, ecgonine methyl ester concentrations ranged from 40 ng mL−1 to 500 ng mL−1 and ecgonine ethyl ester concentrations were found to be in the range 0 ng mL−1 to 180 ng mL−1.
- Published
- 2014
22. Determination of cocaine, its metabolites and pyrolytic products by LC-MS using a chemometric approach
- Author
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Marcelo Gatteli Holler, Renata Pereira Limberger, Andrea Garcia Pereira, Felipe Bianchini D'Avila, Pâmela C. Lukasewicz Ferreira, and Pedro Eduardo Fröehlich
- Subjects
Chromatography ,Central composite design ,General Chemical Engineering ,Electrospray ionization ,General Engineering ,Factorial experiment ,Mass spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Liquid chromatography–mass spectrometry ,Benzoylecgonine ,Ecgonine ,Ammonium acetate - Abstract
A method to assay cocaine (COC), its metabolites benzoylecgonine (BZE), ecgonine (ECG), ecgonine methyl esther (EME), and benzoylnorecgonine (BNE), pyrolytic products anhydroecgonine (AEC) and anhydroecgonine methyl ester (AEME) and adulterant levamisole (LEV) was developed and validated by liquid chromatography-mass spectrometry (LC-MS) using a chemometric approach including a two-level factorial design in the screening step and face-centered central composite design (FCCCD) to achieve the optimization. The method was carried out on positive electrospray ionization (ESI+) with a flow of 1 mL min−1 in isocratic mode consisting of 53% methanol and 47% ammonium acetate 10 mmol L−1 pH 6.3. The chromatographic separation was obtained with a Phenomenex Luna C18(2) column (250 mm × 4.6 mm, particle size 5 μm), with the temperature set at 31 °C. Validation parameters such as specificity, linearity, precision and accuracy were evaluated. The method was linear over the concentration range of 1–100 ng mL−1 for COC, AEME, EME, LEV, BZE and ECG and 5–100 ng mL−1 for AEC and BNE. The method was successfully applied to identify and quantify the analytes.
- Published
- 2014
23. Stability of cocaine and its metabolites in municipal wastewater – the case for using metabolite consolidation to monitor cocaine utilization
- Author
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Katrice A. Lippa and Kevin J. Bisceglia
- Subjects
Health, Toxicology and Mutagenesis ,Metabolite ,Sewage ,Wastewater ,Excretion ,Hydrolysis ,chemistry.chemical_compound ,Cocaine ,Environmental Chemistry ,Ecotoxicology ,Chromatography ,Chemistry ,business.industry ,Environmental engineering ,General Medicine ,Hydrogen-Ion Concentration ,Pollution ,Drug Utilization ,Benzoylecgonine ,Ecgonine ,business ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
Transformations of cocaine and eleven of its metabolites were investigated in untreated municipal sewage at pH ≈ 7 and 9, 23, and 31 °C. Results indicated that hydrolysis-possibly bacterially mediated-was the principal transformation pathway. Residues possessing alkyl esters were particularly susceptible to hydrolysis, with pseudo-first-order rate constants varying from 0.54 to 1.7 day(-1) at 23 °C. Metabolites lacking esters or possessing only a benzoyl ester appeared stable. Residues lacking alkyl esters did accumulate through hydrolysis of precursors, however. As noted previously, this may positively bias cocaine utilization estimates based on benzoylecgonine alone. Reported variability in metabolic excretion was used in conjunction with transformation data to evaluate different approaches for estimating cocaine loading. Results indicate that estimates derived from measurands that capture all major cocaine metabolites, such as COCtot (the sum of all measurable metabolites) and EChyd (the sum of all metabolites that can be hydrolyzed to ecgonine), may reduce uncertainty arising from variability in metabolite transformation and excretion, possibly to ≈ 10 % RSD. This is more than a two-fold reduction relative to estimates derived from benzoylecgonine (26 % RSD), and roughly equivalent to reported uncertainties from sources that are not metabolite-specific (e.g., sampling frequency, flow variability). They and other composite measurands merit consideration from the sewage epidemiology community, beginning with efforts to evaluate the stability of the total cocaine load under realistic sewer conditions.
- Published
- 2013
24. Prescription and illicit psychoactive drugs in oral fluid—LC–MS/MS method development and analysis of samples from Brazilian drivers
- Author
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Paula O. Bohel, Renata Pereira Limberger, Eloisa Dutra Caldas, Maíra Kerpel dos Santos, Flavio Pechansky, Ivomar Zancanaro, and Raquel Brandini De Boni
- Subjects
Adult ,Male ,Automobile Driving ,Prescription Drugs ,Adolescent ,Poison control ,Pharmacology ,Mass Spectrometry ,Pathology and Forensic Medicine ,Heroin ,Forensic Toxicology ,Young Adult ,chemistry.chemical_compound ,Limit of Detection ,Humans ,Medicine ,Ketamine ,Medical prescription ,Saliva ,Aged ,Aged, 80 and over ,Psychotropic Drugs ,Chromatography ,biology ,Illicit Drugs ,business.industry ,Psychoactive drug ,Middle Aged ,biology.organism_classification ,Substance Abuse Detection ,chemistry ,Oral fluid ,Female ,Cannabis ,business ,Ecgonine ,Law ,Brazil ,Chromatography, Liquid ,medicine.drug - Abstract
This study is part of a larger project designed to investigate the prevalence of psychoactive drug (PAD) use among Brazilian drivers. In this paper we describe the development and validation of an analytical method to analyze 32 prescription and illicit PADs (amphetamines, benzodiazepines, cocaine, cannabis, opioids, ketamine and m-CPP) and metabolites in oral fluid samples collected with a Quantisal™ device. Samples were extracted with ethyl acetate:hexane and analyzed by LC-MS/MS. Instrumental LOD ranged from 0.26 to 0.65 ng/mL. Mean procedural recoveries at 1.3 ng/mL (LLOQ) ranged from 50% to 120% for 24 compounds. Recoveries were concentration independent, with the exception of femproporex, heroin and ecgonine methyl-ester (EME) for which the recovery decreased significantly at higher levels (13 and 52 ng/mL). RSD was20% for all compounds at all spiking levels. Ion suppression due to the matrix was20% for most compounds, and higher than 60% for EME and diethylpropion. Analysis was performed against a in-matrix standard curve. About 10% of the 2235 oral fluid samples collected from drivers on Brazilian Federal highways were positive (≥LOD) for at least one analyte investigated. Alone or in combination with other drugs, cocaine/metabolites were the analytes most detected in the samples (129; 5.8%), followed by amphetamines/metabolite (69; 3.1%), benzodiazepines (28; 1.2%), cannabinoids (23; 1.1%) and opioids (8; 0.4%). Detection of at least two PADs from different classes accounted for 9.3% of the 236 positive samples. Cocaine was found at higher levels in the samples (up to 1165 ng/mL). Preventive measures aimed at reducing the use of PADs by drivers in Brazil will certainly contribute to decrease the country's highway death rates.
- Published
- 2012
25. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots
- Author
-
E. Saussereau, Jean-Michel Gaulier, Christian Lacroix, and J.P. Goulle
- Subjects
Electrospray ionization ,Clinical Biochemistry ,Sensitivity and Specificity ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,Drug Stability ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,medicine ,Humans ,Driving under the influence ,Blood Specimen Collection ,Morphine Derivatives ,Chromatography ,Illicit Drugs ,Amphetamines ,celebrities ,Reproducibility of Results ,Cell Biology ,General Medicine ,Dried blood spot ,celebrities.reason_for_arrest ,chemistry ,Benzoylecgonine ,Dried Blood Spot Testing ,Ecgonine ,Chromatography, Liquid ,medicine.drug - Abstract
A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs.
- Published
- 2012
26. A hydrolysis procedure for the analysis of total cocaine residues in wastewater
- Author
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Katrice A. Lippa, A. Lynn Roberts, and Kevin J. Bisceglia
- Subjects
Chromatography ,Chemistry ,Hydrolysis ,Hydrophilic interaction chromatography ,Metabolite ,Solid Phase Extraction ,Extraction (chemistry) ,Tropane ,Waste Disposal, Fluid ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaine ,Wastewater ,Tandem Mass Spectrometry ,Benzoylecgonine ,Humans ,Ecgonine ,Water Pollutants, Chemical ,Chromatography, Liquid - Abstract
We report a sample pretreatment approach for the analysis of total cocaine residues in wastewater that eliminates the need for two key assumptions often made in estimating cocaine utilization from measurement of its benzoylecgonine metabolite: that benzoylecgonine is neither degraded nor generated during transport in a sewer system, and that it is excreted as a constant fraction of cocaine ingested. By adding NaOH and incubating samples at 55 °C, cocaine and its principal metabolites are efficiently hydrolyzed into ecgonine, anhydroecgonine, and norecgonine. Ecgonine, estimated to represent between 37% and 90% (on a molar basis) of cocaine residues, can be directly determined (without preconcentration via solid-phase extraction (SPE)) by reversed-phase (RP) or hydrophilic interaction liquid chromatography-tandem mass spectrometry (LC/MS/MS). If samples are subjected to SPE, anhydroecgonine can also be determined; this metabolite (and its precursors) represents ≈7% of urinary cocaine residues (based on spot collections from living individuals). Although a reference standard for norecgonine is not commercially available, such nortropanes are also a minor fraction (up to 2%) of urinary cocaine residues. The stability of two human markers (cotinine and creatinine) to the hydrolysis procedure was also investigated. Results obtained by applying the hydrolysis approach for the analysis of total cocaine in an untreated municipal wastewater sample (obtained from Baltimore, MD) were generally in excellent agreement with those obtained from split samples analyzed using a more comprehensive solid-phase extraction RPLC/MS/MS method as described in our previous work. In particular, total tropane-based cocaine residues were found to be hydrolyzed to ecgonine with 98-99% efficiency.
- Published
- 2011
27. Cocaine surface contamination and the medico-legal implications of its transfer
- Author
-
Kevin R. McGrath and Frederick P. Smith
- Subjects
Health (social science) ,Drug Contamination ,Sweat patch ,Poison control ,Computer security ,computer.software_genre ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,Contamination ,Environmental health ,Injury prevention ,Medicine ,Drug test ,medicine.diagnostic_test ,business.industry ,Drug testing ,Credit card ,chemistry ,Benzoylecgonine ,business ,Ecgonine ,Law ,computer ,Hair ,medicine.drug - Abstract
The question posed by this research involves how frequently one can expect to contact cocaine in day-to-day living experiences where drug use may not normally be suspected. Issues concerning contamination are germane to medico-legal investigators who evaluate the significance of drug test results in (1) questioned deaths, (2) public health concerns, (3) drugs crimes, and (4) drug use toxicological tests potentially caused by external contamination, such as hair, sweat, and skin swabs. Previous surface studies focus mainly on currency drug contamination; few have addressed other common surfaces. Public surfaces handled by a large number of people, such as building entrance door handles, bank currency dispensing machines, food store shopping carts, and service station fuel pumps within the New Haven, Connecticut metropolitan area were tested. Socio-economically, the distribution of items tested ranged from working-class to upper-middle class areas. Results were obtained using the Securetec Drugwipe II® which is an immunological, on-site test device. Precautions were taken to avoid carry-over and other potential contamination from handling including single-use latex gloves which were pre-tested as a negative control immediately before swabbing. Analysis was performed according to the manufacturer’s instructions and in the laboratory to standardize conditions. Drugwipe II® limit of detection (LOD) is ∼50 ng. Test results revealed 78% positive for cocaine substances as follows: fuel pump buttons for credit card authorization, 100% positive (n = 10 individual locations); ATM machines for currency withdrawal, 100% positive (n = 10 individual locations); grocery store shopping carts, 70% positive; academic building entrance doors, 30% positive (n = 10); and shopping mall entrance/exit doors, 100% positive (n = 5). Forensic scientists and medico-legal investigators responsible for interpreting surface test results are cautioned to consider contamination before ascribing drug activity to a specific individual. For legal proceedings these results are indicative but not conclusive because immunological tests are considered presumptive and may react with the parent substance (cocaine), related compounds (benzoylecgonine, ecgonine methyl ester, ecgonine, nor-ecgonine, and cocaethylene) and immunologically similar materials.
- Published
- 2011
28. The change in the composition of the cocaines in java coca leaves during their growth. The acids of the esters of l-nor-ecgonine from coca leaves
- Author
-
A. W. K. de Jong
- Subjects
chemistry.chemical_compound ,Horticulture ,chemistry ,biology ,Formic acid ,Stereochemistry ,Composition (visual arts) ,General Chemistry ,biology.organism_classification ,Ecgonine ,Coca ,Benzoic acid - Abstract
The contradiction noted previously, that the quantity of the cocaines in the leaves on a branch remains almost constant for 8 successive leaves with the exception of that of the youngest leaf, while the composition of the cocaines in the leaves alters during their growth, - young leaves contain more cinnamylcocaines than cocaine and old leaves more cocaine than cinnamylcocaines, - is explained as being caused by the continuous formation of fresh cocaines in the leaves, and the continuous decomposition of an almost equal quantity of cocaines containing less cocaine and more cinnamylcocaines than the percentages in the fresh formed cocaines. Reasons for the quicker decomposition of the cinnamylcocaines in the leaves are indicated. In agreement with this explanation it is noted, that the acids of the esters of l-nor-ecgonine consist for the main part of formic acid, benzoic acid being not present. The way in which l-nor-formylecgonine can be formed in the leaves from the cinnamylcocaines is indicated.
- Published
- 2010
29. The presence of acid esters of l-nor-ecgonine in coca leaves
- Author
-
A. W. K. de Jong
- Subjects
chemistry.chemical_classification ,biology ,chemistry.chemical_element ,Alcohol ,General Chemistry ,Calcium ,biology.organism_classification ,Coca ,Amino acid ,chemistry.chemical_compound ,Potassium permanganate ,chemistry ,Boiling ,Organic chemistry ,Benzene ,Ecgonine - Abstract
The amino acid formerly1) separated from Java coca leaves is l-nor-ecgonine, which Einhorn has obtained by oxidation of l-ecgonine with potassium permanganate in alkaline solution. It is present in the leaves as acid esters. The calcium salis of these esters and also that of l-nor-ecgonine itself are soluble in the mixture of benzene and methyl alcohol boiling at 58° and also in the mixture of benzene and ethyl alcohol boiling at 68°.
- Published
- 2010
30. Some properties of the ecgonines and their esters I
- Author
-
A. W. K. de Jong
- Subjects
chemistry.chemical_compound ,chemistry ,Boiling ,Inorganic chemistry ,Barium chloride ,Acetone ,Alcohol ,Hydrochloric acid ,General Chemistry ,Ecgonine ,Ecgonidine ,Benzoic acid - Abstract
The specific rotation of l-ecgonine in different solutions is discussed. The decomposition of 0.5g of cocaine in 20 cm3 of 2 n.hydrochloric acid is complete in 5 hours, as is also that of 0.25 g in 20 cm3 of n/2 acid. A method is indicated for the determination of the quantity of l-ecgonine in a mixture containing a compound with leavo rotation, which is not altered by boiling with 20% caustic potash solution. The following principle results were obtained with this method. The quantity of ecgonidine formed by boiling l-ecgonine, l-benzoylecgonine and l-cocaine with hydrochloric acid is greater the stronger the acid and the longer the time of boiling. The esters are split up first into ecgonine and this is then partly transformed into ecgonidine. d-Φ-Ecgonine is not converted by boiling for 12 hours in a strong solution of hydrochloric acid. The l-ecgonine of the esters is partly converted into ecgonidine by boiling with 20% potash. At ordinary temperatures the esters of l-ecgonine are partially converted into d-Φ-ecgonine by alkalis in alcohol or acetone. This is a result of their easy conversion into their d-isomers while they are still undecomposed and in contact with an alkali. By boiling with water benzoylecgonine and also cocaine form only small quantities of ecgonidine. l-Cocaine heated at 115°–120° is converted first to the extent of 50% into ecgonidine methylester and benzoic acid; this acid then forms a benzoate with the remaining 50% of l-cocaine, which is transformed on heating into l-ecgonine methyl ester and benzoic acid anhydride, while the latter ester is changed on longer heating into its d-isomer. d-Cocaine is also transformed by heating at 115–120° into ecgonidine but with much more difficulty. The ecgonines and the cocaines are all converted on heating with excess benzoic acid at 115–120° into ecgonidine. l-Ecgonine forms a compound with barium chloride (2 mol. of ecgonine + 1 mol. of BaCl2) which is slightly soluble in boiling absolute alcohol, but insoluble in boiling benzene.
- Published
- 2010
31. The absence of l-benzoylecgonine and the presence of an ester very probably the methylester of l-ecgonine in java coca leaves
- Author
-
A. W. K. de Jong
- Subjects
Chromatography ,biology ,Java ,Chemistry ,Stereochemistry ,fungi ,information science ,food and beverages ,General Chemistry ,biology.organism_classification ,Coca ,chemistry.chemical_compound ,health services administration ,Benzoylecgonine ,natural sciences ,Ecgonine ,computer ,computer.programming_language - Abstract
Methods are indicated by which the absence of l-benzoylecgonine and the presence of an ester of l-ecgonine in Java coca leaves can be established.
- Published
- 2010
32. Some properties of the ecgonines and their esters V: Conversion of 1-ecgonine in aqueous solutions
- Author
-
A. W. K. de Jong
- Subjects
chemistry.chemical_classification ,Aqueous solution ,Potassium ,Inorganic chemistry ,chemistry.chemical_element ,Salt (chemistry) ,Hydrochloric acid ,General Chemistry ,Iodine ,Alkali metal ,Chloride ,chemistry.chemical_compound ,chemistry ,medicine ,Ecgonine ,medicine.drug - Abstract
By heating l-ecgonine in weakly acidified aqueous solution and also in strong hydrochloric acid solution, l-ecgonine is converted to the extent of 10.5-12.5% into d-φ-ecgonine, an equilibrium mixture of ecgonines being formed. Both l- and d-φ-ecgonine give black crystals like l-ecgonidine with hydriodic acid solution containing iodine; these crystals, when boiled with water, give solutions which show respectively leavo- and dextro-gyratory rotations. On boiling l-ecgonine as an alkali-salt in saturated alkali chloride solution, another equilibrium is reached between the ecgonines; the sodium salt gave a 86.9% conversion into d-φ-ecgonine, the potassium salt one of 69% and the calcium salt one of 78.5%.
- Published
- 2010
33. A complete extraction of the bases and the acid esters of l-nor-ecgonine from coca leaves
- Author
-
A. W. K. de Jong
- Subjects
Solvent ,chemistry.chemical_compound ,Ammonia ,chemistry ,Inorganic chemistry ,Anhydrous ,Ether ,Hydrochloric acid ,General Chemistry ,Calcium oxide ,Ecgonine ,Benzene - Abstract
The leaves, 20 g. are mixed with finely pulverised quick lime, containing a quantity of calcium oxide corresponding exactly with the moisture content of the leaves. After remaining for 24 hours in a closed flask they are transferred to an extractor containing a mixture of 100 cm3 of anhydrous benzene and 5 cm3 of absolute methyl alcohol. A quantity of ammonia solution, containing exactly 1.938 g of water is added and the leaves mixed with the solvents. After 24 hours, finely pulverised quick lime possessing a quantity of calcium oxide corresponding with the quantity of water used in the ammonia solution is added and after mixing, the extractor closed until the following day. Percolation is then started in a slow rate. As soon as the solvent mixture is run down a quantity of the mixture of anhydrous benzene and absolute methyl alcohol boiling at 58° is added to the leaves. Percolation with this solvent mixture is finished when the percolate mesures 800 cm3. The mixture boiling at 58° is distilled from this percolate and the remaining benzene solution is filtered from the calcium salts insoluble in benzene. The residue from the benzene solution is shaken with 25 cm3 of n/5 HCl solution and 100 cm3 of ether. The quantity of bases, the cocaines and the methyl ester of ecgonine can be determined in the hydrochloric acid solution so obtained. The quantity of l-nor-ecgonine can be determined in the mixture of calcium salts.
- Published
- 2010
34. Some properties of the ecgonines and their esters. VI. The calcium and lead salts of l-ecgonine, the conversion of l-ecgonine into l-benzoylecgonine and its esterification with methyl alcohol and benzoic anhydride or benzoyl chloride
- Author
-
A. W. K. de Jong
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,Benzoyl chloride ,chemistry ,Benzoylecgonine ,Anhydrous ,Salt (chemistry) ,Organic chemistry ,Alcohol ,General Chemistry ,Benzene ,Ecgonine ,Benzoic anhydride - Abstract
The calcium salt of l-ecgonine is soluble in methyl and ethyl alcohols and also in anhydrous benzene. It crystallises in fine needles. Ecgonine forms a compound with calcium chloride. The lead salt also crystallises in needles and is readily soluble in alcohol and benzene. An almost complete conversion of l-ecgonine into l-benzoylecgonine is obtained in 5 days at ordinary temperature in aqueous acetone with the addition of 2–3 times the theoretical quantity of benzoic anhydride. By the action of benzoic anhydride and methyl alcohol on benzoylecgonine at ordinary temperature the anhydride of benzoylecgonine is formed as the main product, which can then give cocaine and benzoylecgonine with methyl alcohol. The conversion into cocaine obtained, however, by using 7 times the theoretical quantity of benzoic anhydride was only 80%. Benzoylecgonine when treated with methyl alcohol and 3.5 times the theoretical quantity of benzoyl chloride at ordinary temperature gives an almost complete conversion into cocaine.
- Published
- 2010
35. Configuration and conformation of all four cocaines from nmr spectra
- Author
-
Leendert Maat, A. J. van der Gugten, A. Sinnema, and H. C. Beyerman
- Subjects
NMR spectra database ,chemistry.chemical_compound ,chemistry ,Stereochemistry ,Tropane ,General Chemistry ,Piperidine ,Nuclear magnetic resonance spectroscopy ,Ring (chemistry) ,Ecgonine - Abstract
The configurations of (±)-allococaine and (±)-allopseudococaine have been determined, for the first time in an unambiguous way, by means of NMR spectroscopy. The known configurations of (±)-cocaine and (±)-pseudococaine receive independent confirmation. The preferential conformation of the piperidine ring of the tropane nucleus is found to be the chair form in all four isomers, and also in the methyl esters of the four corresponding isomers of ecgonine. The preparation of (±)-allococaine and (±)-allopseudococaine has been improved.
- Published
- 2010
36. Simultaneous Liquid Chromatography-Mass Spectrometry Quantification of Urinary Opiates, Cocaine, and Metabolites in Opiate-Dependent Pregnant Women in Methadone-Maintenance Treatment
- Author
-
Riet Dams, Marilyn A. Huestis, Hendrée E. Jones, Robin E. Choo, and Diaa M. Shakleya
- Subjects
Adult ,Narcotics ,Spectrometry, Mass, Electrospray Ionization ,Urinalysis ,Health, Toxicology and Mutagenesis ,Urine ,Pharmacology ,Toxicology ,Article ,Analytical Chemistry ,Cocaine-Related Disorders ,Young Adult ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,Pregnancy ,medicine ,Humans ,Environmental Chemistry ,Chromatography, High Pressure Liquid ,Morphine Derivatives ,Chemical Health and Safety ,Chromatography ,medicine.diagnostic_test ,Codeine ,Opioid-Related Disorders ,Substance Abuse Detection ,chemistry ,Benzoylecgonine ,Morphine ,Female ,Opiate ,Ecgonine ,Methadone ,medicine.drug - Abstract
Opiates, cocaine, and metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10-50 microg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10-100 microg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 microg/L), codeine (2000 microg/L), 6-acetylmorphine (10 microg/L), and benzoylecgonine (100 microg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 microg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC-MS as compared to gas chromatography-mass spectrometry analysis.
- Published
- 2010
37. The hydrated and anhydrous gold(III) tetrachloride salts of<scp>L</scp>-ecgonine, an important forensic toxicology marker for cocaine
- Author
-
Matthew R. Wood, Thomas A. Brettell, Hugh W. Thompson, and Roger A. Lalancette
- Subjects
chemistry.chemical_classification ,Molecular Structure ,Hydronium ,Inorganic chemistry ,Water ,Salt (chemistry) ,General Medicine ,Crystal structure ,Crystallography, X-Ray ,Medicinal chemistry ,Gold Compounds ,General Biochemistry, Genetics and Molecular Biology ,Solvent ,Forensic Toxicology ,chemistry.chemical_compound ,Cocaine ,chemistry ,Anhydrous ,Humans ,Molecule ,Salts ,Ecgonine ,Hydrate - Abstract
The structure of the hydrated gold(III) tetrachloride salt of L-ecgonine {hydronium tetrakis[(1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2.1]octane-2-carboxylate pentakis[tetrachloridoaurate(III)] hexahydrate}, (C(9)H(16)NO(3))(4)(H(3)O)[AuCl(4)](5).6H(2)O, demonstrates an unprecedented stoichiometric relationship between the cations and anions in the unit cell. The previous tropane alkaloid structures, including the related hydrochloride salts, all have a cation-anion ratio of 1:1, as does the anhydrous salt described here, namely (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2.1]octane-2-carboxylate tetrachloridoaurate(III), (C(9)H(16)NO(3))[AuCl(4)]. The hydrated salt, however, consists of four monopositive N-protonated units of the alkaloid and five [AuCl(4)](-) counter-ions, plus seven solvent water molecules. The H atom required for change balance has been assigned to a water molecule. In addition, the hydrate has a novel arrangement, with all seven of the water molecules and all of the O atoms in the cations participating in an alternating arrangement of interleaved sheets of the anionic species. Both the hydrate and the anhydrous salt of the same toxicologically important marker for cocaine show that the cation and anion are in close proximity to each other, as was found in the gold(III) tetrachloride salt of L-cocaine.
- Published
- 2009
38. An automated SPE/LC/MS/MS method for the analysis of cocaine and metabolites in whole blood☆
- Author
-
Madeline A. Montgomery, Eshwar Jagerdeo, Martin Sibum, and Marc A. LeBeau
- Subjects
Analyte ,Chromatography ,Solid Phase Extraction ,Clinical Biochemistry ,Selected reaction monitoring ,Analytical chemistry ,Reproducibility of Results ,Cell Biology ,General Medicine ,Tandem mass spectrometry ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,chemistry ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,medicine ,Benzoylecgonine ,Humans ,Solid phase extraction ,Ecgonine ,Chromatography, High Pressure Liquid ,medicine.drug - Abstract
As laboratories are called upon to develop novel, fast, and sensitive methods, here we present a completely automated method for the analysis of cocaine and its metabolites (benzoylecgonine, ecgonine methyl ester, ecgonine and cocaethylene) from whole blood. This method utilizes an online solid-phase extraction (SPE) with high performance liquid chromatographic separation and tandem mass spectrometric detection. Pretreatment of samples involve only protein precipitation and ultracentrifugation. An efficient online solid-phase extraction (SPE) procedure was developed using Hysphere MM anion sorbent. A gradient chromatography method with a Gemini C6-Phenyl (50mmx3.00mm i.d., 5microm) column was used for the complete separation of all components. Analysis was by positive ion mode electrospray ionization tandem mass spectrometry, using multiple reaction monitoring (MRM) to enhance the selectivity and sensitivity of the method. For the analysis, two MRM transitions are monitored for each analyte and one transition is monitored for each internal standard. With a 30-microL sample injection, linearity was analyte dependent but generally fell between 8 and 500ng/mL. The limits of detection (LODs) for the method ranged from 3 to 16ng/mL and the limits of quantitation (LOQs) ranged from 8 to 47ng/mL. The bias and precision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrate bias as7%, and %precision as9% for all components at each QC level.
- Published
- 2008
39. Separation and Detection of Narcotic Drugs on a Microchip Using Micellar Electrokinetic Chromatography and Electrochemiluminescence
- Author
-
Yan Du and Erkang Wang
- Subjects
endocrine system ,Analyte ,Chromatography ,Micellar electrokinetic chromatography ,Analytical Chemistry ,Electrophoresis ,chemistry.chemical_compound ,Capillary electrophoresis ,chemistry ,Electrochemistry ,Electrochemiluminescence ,Solid phase extraction ,Sodium dodecyl sulfate ,Ecgonine - Abstract
A new approach for fast and sensitive electrochemiluminescence (ECL) detection of narcotic drugs on a microchip after separation by micellar electrokinetic chromatography (MEKC) is presented, taking the cocaine and its hydrolysate ecgonine as the test analytes. The mixture of hydrophilic BMIMBF4 ionic liquid (IL) and sodium dodecyl sulfate (SDS) was used directly as the buffer of MEKC with less noisy baselines, lower electrophoretic current and satisfactory separation performance.
- Published
- 2008
40. Cocaine and Metabolites Urinary Excretion after Controlled Smoked Administration*
- Author
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Daniel V. Trinidad, Aaron J. Jacobs, Buddha D. Paul, Edward J. Cone, Marilyn A. Huestis, Amanda J. Jenkins, Shairose Lalani, Eric T. Shimomura, W. David Darwin, and Michael L. Smith
- Subjects
Adult ,Male ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Metabolite ,Urine ,Pharmacology ,Toxicology ,Placebo ,Gas Chromatography-Mass Spectrometry ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Pharmacokinetics ,medicine ,Humans ,Environmental Chemistry ,Inhalation Exposure ,Chemical Health and Safety ,Chromatography ,Dose-Response Relationship, Drug ,Local anesthetic ,Alkaloid ,Smoking ,Substance Abuse Detection ,chemistry ,Benzoylecgonine ,Crack Cocaine ,Ecgonine - Abstract
Understanding cocaine and metabolites urinary excretion following smoking is important for interpretation of urine test results in judicial, workplace and treatment settings. In National Institute on Drug Abuse approved studies on a secure research unit, six subjects smoked placebo, 10, 20, and 40 mg cocaine with a precise dose delivery device and six different subjects smoked 42 mg cocaine in a glass pipe. Urine specimens (n = 700) were collected for up to seven days and analyzed for cocaine (COC), benzoylecgonine (BE), ecgonine methylester (EME), m-hydroxybenzoylecgonine (mOHBE), p-hydroxybenzoylecgonine (pOHBE), norbenzoylecgonine (NBE), and ecgonine (EC) by gas chromatography–mass spectrometry. Results (mean ± SE) for the 40-mg precise delivery doses are as follows: COCBEEMEmOHBEpOHBENBEECCutoff(ng/mL)10201025252550Cmax(ng/mL)4085±23039196±15694638±1548222±69540±227614±347852±211Tmax(h)2.2±0.36.6±0.95.6±1.47.8±0.54.4±1.56.0±2.09.3 ±1.3Lastpositive(h)5510616455553280 Mean Cmax for all analytes linearly increased with increasing dose. Tmax was not dose-dependent. All metabolites were detected in some subjects within 2 h. EC concentrations were significantly higher after smoked cocaine in a precise delivery coil compared to a glass “crack” pipe.
- Published
- 2007
41. Bioanalytical procedures for determination of drugs of abuse in blood
- Author
-
Liane D. Paul and Thomas Kraemer
- Subjects
Chromatography ,Bioanalysis ,Metabolite ,Forensic toxicology ,Toxicology ,Biochemistry ,Chemistry Techniques, Analytical ,Analytical Chemistry ,Norcocaine ,Substance Abuse Detection ,chemistry.chemical_compound ,Cocaethylene ,Pharmaceutical Preparations ,chemistry ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,medicine ,Benzoylecgonine ,Humans ,Ecgonine ,medicine.drug - Abstract
Determination of drugs of abuse in blood is of great importance in clinical and forensic toxicology. This review describes procedures for detection of the following drugs of abuse and their metabolites in whole blood, plasma or serum: Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, 11-nor-9-carboxy-Delta9-tetrahydrocannabinol, 11-nor-9-carboxy-Delta9-tetrahydrocannabinol glucuronide, heroin, 6-monoacetylmorphine, morphine, morphine-6-glucuronide, morphine-3-glucuronide, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, ecgonine methyl ester, cocaethylene, other cocaine metabolites or pyrolysis products (norcocaine, norcocaethylene, norbenzoylecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine, ethyl ecgonine, ecgonine, anhydroecgonine methyl ester, anhydroecgonine ethyl ester, anhydroecgonine, noranhydroecgonine, N-hydroxynorcocaine, cocaine N-oxide, anhydroecgonine methyl ester N-oxide). Metabolites and degradation products which are recommended to be monitored for assessment in clinical or forensic toxicology are mentioned. Papers written in English between 2002 and the beginning of 2007 are reviewed. Analytical methods are assessed for their suitability in forensic toxicology, where special requirements have to be met. For many of the analytes sensitive immunological methods for screening are available. Screening and confirmation is mostly done by gas chromatography (GC)-mass spectrometry (MS) or liquid chromatography (LC)-MS(/MS) procedures. Basic information about the biosample assayed, internal standard, workup, GC or LC column and mobile phase, detection mode, and validation data for each procedure is summarized in two tables to facilitate the selection of a method suitable for a specific analytic problem.
- Published
- 2007
42. Cocaine profiling for strategic intelligence purposes, a cross-border project between France and Switzerland
- Author
-
Pierre Esseiva, P. Hayoz, Laurence Dujourdy, Fabrice Besacier, Pierre Margot, and S. Lociciro
- Subjects
Pre treatment ,Chromatography ,Operations research ,Ecgonine methyl ester ,Drug profiling ,Pathology and Forensic Medicine ,Norcocaine ,chemistry.chemical_compound ,chemistry ,Benzoylecgonine ,Profiling (information science) ,Ecgonine ,Law ,Retention time - Abstract
Optimisation and harmonisation of analytical and statistical methodology have been carried out between two forensic laboratories (Lausanne, CH and Lyon, F) in order to provide drug intelligence for cross-border cocaine seizures. The aim was to improve the gas chromatographic analysis of cocaine samples for profiling. Some important validation parameters were tested to verify the developed method and demonstrate its profiling capacity: the selectivity of the method with retention time reproducibility, the choice of a derivatisation agent improving the chromatography (MSTFA, BSA, TMSI and BSTFA + TMCS 1%), the cutting agents influence (matrix effect), the influence of the sample storage conditions and the sample quantity to weigh for analyses. Eight main alkaloids, which represent the sample signature, have been selected: ecgonine methyl ester, ecgonine, tropacocaine, benzoylecgonine, norcocaine, cis- and trans-cinnamoylcocaine and 3,4,5-trimethoxycocaine. Their stability in the solvent used (CHCl3/pyridine) was demonstrated. In order to reach the final objective, which is the comparison of samples seized and analyzed in two different laboratories, the harmonisation of the profiling method between the two laboratories had to be ensured and is the subject of ongoing research.
- Published
- 2007
43. Simultaneous determination of traditional and emerging illicit drugs in sediments, sludges and particulate matter
- Author
-
Vicente Andreu, R. Álvarez-Ruiz, Yolanda Picó, María Jesús Andrés-Costa, and Ministerio de Economía y Competitividad (España)
- Subjects
Drugs of abuse ,Tandem mass spectrometry ,Liquid chromatography ,Dimethyltryptamine ,Biochemistry ,Analytical Chemistry ,Designer Drugs ,chemistry.chemical_compound ,Cocaethylene ,Liquid chromatography–mass spectrometry ,medicine ,Solid phase extraction ,Ephedrine ,Solid-phase extraction ,Chromatography ,Sewage ,Illicit Drugs ,Organic Chemistry ,Extraction (chemistry) ,Solid Phase Extraction ,General Medicine ,chemistry ,Benzoylecgonine ,Ultrasound assisted extraction ,Particulate Matter ,Abiotic environmental samples ,Ecgonine ,medicine.drug ,Chromatography, Liquid - Abstract
An analytical method for determining traditional and emerging drugs of abuse in particulate matter, sewage sludge and sediment has been developed and validated. A total of 41 drugs of abuse and metabolites including cocainics, tryptamines, amphetamines, arylcyclohexylamines, cathinones, morphine derivatives, pyrrolidifenones derivatives, entactogens, piperazines and other psychostimulants were selected. Samples were ultrasound extracted with McIlvaine buffer and methanol, and the extracts were cleaned up by solid phase extraction (SPE) using Strata-X cartridges. Drugs were eluted using methanol and methanol-dichloromethane and determined by liquid chromatography tandem mass spectrometry. The optimum solid-liquid extraction (SLE) conditions were: weight 1g of sample and ultrasound assisted extraction (UAE) with 10mL of methanol-McIlvain buffer (1:1, v/v, pH 4.5) for 10min. Recoveries for all compounds were ≥50% in the three matrices with the exception of ephedrine (EPHE), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), ecgonine methyester (ECME), heroin (HER), 3,4-methylendioxyamphetamine (MDA) and 4-acetoxy N,N'-dimethyltryptamine (4-AcO-DIPT) and methadone (MET). Data acquisition was done by selective reaction monitoring (SRM), and the two most abundant product ions were used for confirmation. Limits of detection were lower than 1.32ngg-1 dry weight (d.w.) and limits of quantification were between 0.12 and 3.96ngg-1 (d.w.). The method was applied to the analysis of particulate matter, where cocaine (COC), benzoylecgonine (BECG), ecgoninemethylester (ECME), cocaethylene (COCET), methadone (MET) and codeine (COD) were mostly detected. In the case of dehydrated sludge, opioids are at higher concentration than cocainics and some emerging drugs such as 4-methoxyamphetamine (PMA), ketamine (KET) and bufotenine (BUF) were detected. In sediment COC, 4-methoxyphencyclidine (4-MeO-PCP), MET and BECG were most relevant compounds. © 2015 Elsevier B.V., This work has been supported by the Spanish Ministry of Economy and Competitiveness through the projects (GCL2011-29703-C02-02). M. Jesús Andrés-Costa also thanks the Spanish Ministry for the FPI grant.
- Published
- 2015
44. Cardiac Depression Induced by Cocaine or Cocaethylene are Alleviated by Lipid Emulsion More Effectively Than by Sulfobutylether β-Cyclodextrin
- Author
-
Katarzyna Kowal, Guy L. Weinberg, Douglas L. Feinstein, Adrian Pichurko, Bocheng Lin, Israel Rubinstein, David E. Schwartz, Michael R. Fettiplace, Kinga Lis, and Richard Ripper
- Subjects
Male ,Fat Emulsions, Intravenous ,medicine.drug_class ,Beta-Cyclodextrins ,Pharmacology ,Article ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,Heart Rate ,Coronary Circulation ,medicine ,Animals ,Cardiotoxicity ,Local anesthetic ,business.industry ,beta-Cyclodextrins ,Arrhythmias, Cardiac ,Heart ,General Medicine ,medicine.disease ,Bupivacaine ,Myocardial Contraction ,Rats ,chemistry ,Anesthesia ,Depression, Chemical ,Toxicity ,Emergency Medicine ,Benzoylecgonine ,Cocaine intoxication ,Ecgonine ,business ,medicine.drug - Abstract
Objectives Cocaine intoxication leads to over 500,000 emergency department visits annually in the United States and ethanol cointoxication occurs in 34% of those cases. Cardiotoxicity is an ominous complication of cocaine and cocaethylene overdose for which no specific antidote exists. Because infusion of lipid emulsion (Intralipid) can treat lipophilic local anesthetic toxicity and cocaine is an amphipathic local anesthetic, the authors tested whether lipid emulsion could attenuate cocaine cardiotoxicity in vivo. The effects of lipid emulsion were compared with the metabolically inert sulfobutylether-β-cyclodextrin (SBE-β-CD; Captisol) in an isolated heart model of cocaine and cocaethylene toxicity to determine if capture alone could exert similar benefit as lipid emulsion, which exhibits multimodal effects. The authors then tested if cocaine and cocaethylene, like bupivacaine, inhibit lipid-based metabolism in isolated cardiac mitochondria. Methods For whole animal experiments, Sprague-Dawley rats were anesthetized, instrumented, and pretreated with lipid emulsion followed by a continuous infusion of cocaine to assess time of onset of cocaine toxicity. For ex vivo experiments, rat hearts were placed onto a nonrecirculating Langendorff system perfused with Krebs-Henseleit solution. Heart rate, left ventricle maximum developed pressure (LVdevP), left ventricle diastolic pressure, maximum rate of contraction (+dP/dtmax), maximum rate of relaxation (–dP/dtmax), rate-pressure product (RPP = heart rate × LVdevP), and line pressure were monitored continuously during the experiment. A dose response to cocaine (10, 30, 50, and 100 μmol/L) and cocaethylene (10, 30, and 50 μmol/L) was generated in the absence or presence of either 0.25% lipid emulsion or SBE-β-CD. Substrate-specific rates of oxygen consumption were measured in interfibrillar cardiac mitochondria in the presence of cocaine, cocaethylene, ecgonine, and benzoylecgonine. Results Treatment with lipid emulsion delayed onset of hypotension (140 seconds vs. 279 seconds; p = 0.008) and asystole (369 seconds vs. 607 seconds; p = 0.02) in whole animals. Cocaine and cocaethylene induced dose-dependent decreases in RPP, +dP/dtmax, and –dP/dtmaxabs (p
- Published
- 2015
45. Naturally Occurring and Nasty
- Author
-
Li Meng and Lauren Partyka
- Subjects
business.industry ,Local anesthetic ,medicine.drug_class ,Propranolol ,Pharmacology ,Hypertensive crisis ,chemistry.chemical_compound ,chemistry ,Coronary Artery Vasospasm ,Cocaine toxicity ,Toxicity ,medicine ,business ,Ecgonine ,medicine.drug - Abstract
This case discusses the pharmacodynamic interaction between cocaine and propranolol, resulting in hypertension and exaggerated cocaine toxicity.
- Published
- 2015
46. Evaluation of isotopically labeled internal standards and methods of derivatization for quantitative determination of cocaine and related compounds
- Author
-
Meng-Yen Wu, Ray H. Liu, Russell J. Lewis, Sheng-Meng Wang, and Dennis V. Canfield
- Subjects
Analyte ,Chromatography ,Biochemistry (medical) ,Toxicology ,Mass spectrometry ,Pathology and Forensic Medicine ,Norcocaine ,chemistry.chemical_compound ,Cocaethylene ,chemistry ,Benzoylecgonine ,medicine ,Gas chromatography–mass spectrometry ,Ecgonine ,Derivatization ,medicine.drug - Abstract
Gas chromatography-mass spectrometry (GCMS) is the preferred method for the analysis of drugs/metabolites in biological specimens with use of isotopically labeled analogs of the analytes as internal standards (ISs). An important aspect of the chemical derivatization (CD) for GC-MS analysis is that the CD products derived from the analyte and the selected IS must generate ions suitable for designating the analyte and the IS. These ions should not have significant cross contribution (CC), i.e., IS contribution to the intensities of the ions designated for the analyte, and vice versa. With this in mind, the authors have conducted a search of isotopically labeled analogs of commonly abused cocaine and related compounds (cocaine, norcocaine, benzoylecgonine, cocaethylene, ecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) that are commercially available. These ISs and analytes were derivatized with various groups of reagents, and the CD products were analyzed by GC-MS. MS data are presented in two forms: (1) systematic presentation of fullscan spectra; and (2) tabulation of CC data for ions with potential for designating the ISs and analytes. Many (if not most) of these full-scan spectra are not yet available in the open literature and should be of routine reference value to forensic and clinical laboratories that are engaged in the analysis of these drugs/metabolites. Fullscan MS data were further used to select ion pairs with potential for designating the analytes and ISs in quantitative analysis protocols. The CC data of these ion pairs were evaluated using data collected under the selected ion-monitoring mode and summarized in table format. The data exhibited similar CC characteristics in each alkyl, acetyl, or TMS series. Among the potentially usable ion pairs derived from a specific CD group, there was a trend that the ion pairs with higher mass showed better CC data. The CC data derived from the use of ISs labeled with more deuterium atoms were generally more favorable. These data should save enormous amounts of time and effort for practicing laboratories in their search for optimal analytical parameters.
- Published
- 2006
47. Evaluation and Management of the Patient Who Has Cocaine-associated Chest Pain
- Author
-
Timothy D. Henry and Judd E. Hollander
- Subjects
Male ,Chest Pain ,Narcotic ,medicine.drug_class ,medicine.medical_treatment ,Myocardial Infarction ,Risk Assessment ,Severity of Illness Index ,Cocaine-Related Disorders ,Electrocardiography ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,medicine ,Humans ,Local anesthesia ,business.industry ,Local anesthetic ,Alkaloid ,General Medicine ,Combined Modality Therapy ,Norcocaine ,Survival Rate ,Treatment Outcome ,chemistry ,Evaluation Studies as Topic ,Anesthesia ,Benzoylecgonine ,Female ,Cardiology and Cardiovascular Medicine ,business ,Ecgonine ,Follow-Up Studies ,medicine.drug - Abstract
Erythroxylon coca, the shrub from which co-caine is naturally derived, grows indigenously inSouth America. Cocaine was first identified asthe active alkaloid in the coca leaf in 1857. Asfar back as the twelfth century, Incas used co-caine-filled saliva as local anesthesia for ritualtrephinations [1]. In 1884, it was recognized med-ically as a local anesthetic [2]. In the early twenti-eth century, cocaine was used briefly as aningredient in Coca-Cola. In 1906, the UnitedStates began to control cocaine use, and in 1914the Harrison Narcotic Act labeled cocaine asa narcotic. It became a schedule II drug in the1970s. During the last several decades, recreation-al cocaine use has increased, and reports of sideeffects have grown exponentially. As of 2003,34.9 million citizens of the United States(14.7%) have used cocaine at least once, with2.3 million citizens using cocaine within the pastmonth [3].PharmacologyCocaine is absorbed through application to themucosa, ingestion, inhalation, and direct intrave-nous injection. Effects from nasal insufflationbegin rapidly with peak concentrations typicallyreached within 30 to 60 minutes. Intravenousand inhalational routes of cocaine use producenear-immediate distribution throughout the cir-culation. ‘‘Crack’’ is the direct precipitate offree-base cocaine that results from alkalinizationof aqueous cocaine hydrochloride.The relative contributions of cocaine and itsmetabolites to the clinical effects remain some-what unclear. Cocaine is hydrolyzed rapidly byliver and plasma esterases to ecgonine methylester(EME), which accounts for 30% to 50% of theparent product. Nonenzymatic hydrolysis resultsin the formation of the other major metabolite,benzoylecgonine (approximately 40% of the par-ent product). The biologic half-life of cocaine is0.5 to 1.5 hours; Benzoylecgonine and EME, themajor metabolites of cocaine, have half-lives of 5to 8 hours and 3.5 to 6 hours, respectively [4].Minor metabolites, norcocaine and ecgonine,account for the majority of the other degradationproducts. Early studies suggested that cocaine andnorcocaine accounted for majority of the vasculareffects of cocaine [5]. Recent studies, however,demonstrate an active role for many of the metab-olites. Most studies suggest that cocaine and nor-cocaine are the most potent vasoconstrictors;benzoylecgonine and ecgonine have less of an ef-fect. Some studies suggest that EME may resultin mild cerebral vasodilation [6,7]. Sodium-chan-nel antagonist effects occur with cocaine and nor-cocaine [8]. Sodium-channel antagonist effects donot occur with benzoylecgonine or EME [8].Cocaethyleneisauniquemetabolitethatresultsfrom the combined use of alcohol and cocaine [9].In clinical studies, cocaethylene produces hemody-namic effects comparable to those of cocaine. Co-caethylene has a direct myocardial depressanteffect [10] that is independent of any coronary
- Published
- 2006
48. Analysis of cocaine and three of its metabolites in hair by gas chromatography-mass spectrometry using ion-trap detection for CI/MS/MS
- Author
-
Emmanuelle Cognard, Stéphane Bouchonnet, Christian Staub, Serge Rudaz, Institute of Forensic Medicine, affiliation inconnue, Laboratory of Pharmaceutical Analytical Chemistry, Laboratoire des mécanismes réactionnels (DCMR), and École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Adult ,Male ,Adolescent ,Clinical Biochemistry ,02 engineering and technology ,Mass spectrometry ,Sensitivity and Specificity ,01 natural sciences ,Biochemistry ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaethylene ,Cocaine ,medicine ,Humans ,Solid phase extraction ,Detection limit ,Chemical ionization ,Chromatography ,Chemistry ,010401 analytical chemistry ,Reproducibility of Results ,Cell Biology ,General Medicine ,Middle Aged ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Calibration ,Female ,Gas chromatography ,Gas chromatography–mass spectrometry ,0210 nano-technology ,Ecgonine ,Hair ,medicine.drug - Abstract
International audience; A sensitive GC/CI/MS/MS method was developed for the simultaneous determination of cocaine (COC), anhydroecgonine methylester (cocaine pyrolysis product, AEME), ecgonine methylester (cocaine enzymatic hydrolysis product, EME) and cocaethylene (cocaine with ethanol trans-esterification product, COET) in human hair samples. After acid hydrolysis, hair samples were extracted with an automated solid phase extraction (SPE). The analysis of cocaine and its three metabolites was performed using an ion-trap spectrometer in positive chemical ionization with isobutane as gas reagent. The procedure was validated. Weighted linear regression was found appropriate in a concentration range of 0.10-5.00 ng/mg for AEME, 0.05-5.00 ng/mg for COC, EME and COET. The limit of detection was estimated at 0.005 ng/mg for COC and COET, at 0.025 ng/mg for EME, and at 0.050 ng/mg for AEME. Method performance was evaluated in terms of trueness and precision using quality control (QC) samples over the investigated ranges. Method selectivity and robustness were also demonstrated.
- Published
- 2005
49. Gender differences in cocaine pharmacokinetics in CF-1 mice
- Author
-
Rita M. Turkall, Thomas Visalli, and Mohamed S. Abdel-Rahman
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Pharmacology ,Toxicology ,Mice ,chemistry.chemical_compound ,Cocaine ,Pharmacokinetics ,Internal medicine ,medicine ,Animals ,Tissue Distribution ,Biotransformation ,Chromatography, High Pressure Liquid ,Sex Characteristics ,Kidney ,Local anesthetic ,General Medicine ,Metabolism ,Norcocaine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Toxicity ,Benzoylecgonine ,Female ,Indicators and Reagents ,Chemical and Drug Induced Liver Injury ,Ecgonine - Abstract
Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed. Male and female CF-1 mice were orally administered 20 mg/kg cocaine hydrochloride once daily for 7 days. Blood samples were withdrawn at various time points post-injection and analyzed for cocaine and its metabolites benzoylecgonine (BE), norcocaine, ecgonine methyl ester (EME), and ecgonine (E). In addition, tissue concentrations of cocaine and its metabolites were determined in liver, heart, brain, and kidney tissue. The results demonstrated that the plasma elimination half-life of cocaine is nearly three times longer in males versus females. Non-hepatotoxic hydrolysis metabolites BE, EME, and E were higher in female tissues while norcocaine was detected in tissues of male animals only. This study revealed that differences in cocaine pharmacokinetics and the resultant differences in the biodisposition of cocaine and its metabolites in tissues contribute to the mechanism of gender difference seen in cocaine hepatotoxicity.
- Published
- 2005
50. Detecting Cocaine Use Through Sweat Testing: Multilevel Modeling of Sweat Patch Length-of-Wear Data
- Author
-
Bruce D. Johnson, Neil Fortner, and Hilary James Liberty
- Subjects
Adult ,Male ,Analyte ,Time Factors ,Stereochemistry ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Urine ,Toxicology ,Article ,Analytical Chemistry ,SWEAT ,chemistry.chemical_compound ,Cocaine ,medicine ,Humans ,Environmental Chemistry ,Sweat ,Sweat test ,Chemical Health and Safety ,medicine.diagnostic_test ,Local anesthetic ,Substance Abuse Detection ,chemistry ,Anesthesia ,Benzoylecgonine ,Ecgonine - Abstract
Although urine analysis remains the standard for detection of drugs of abuse, sweat patches provide a convenient alternative that avoids some of the problems with drug testing such as violations of privacy in observed urination, possibility of disease transmission, and transport of noxious fluids. This study examined minimum length of wear necessary to detect recent or concurrent cocaine use in a convenience sample of active cocaine users and also differences in analyte concentrations with increasing longer-term wear. Twenty-seven subjects (22 active drug users and 5 comparison subjects who did not use drugs) wore short-term ((1/2)h, 1 h, 1(1/2) h, and 2 h), then long-term patches (1, 3, 7, and 14 day). Short- and long-term patches were identical except for duration of wear. The predominant analyte found was cocaine, followed by benzoylecgonine, then ecgonine methylester. The minimum duration that patches must be worn to detect recent or concurrent cocaine use in this sample is more than 2 h and less than or equal to 1 day. Analyte concentrations increase significantly with increasing lengths of wear. However, increases between the one-week and two-week patches were significant for benzoylecgonine only.
- Published
- 2004
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