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Morphine suppresses respiration for longer periods of time when it is injected into the spinal column than when it is given intravenously. This indicates that morphine and other opioids can directly affect the central nervous system.

Drug testing is a useful tool to identify drug use or monitor adherence to prescription drugs. The interpretation of drug results can be complicated based on the pattern and proportional concentrations of drugs and/or drug metabolite(s). The purpose of this retrospective study was to detect the positivity rates and metabolic patterns of five prescription drugs, including fentanyl, meperidine, methylphenidate, tapentadol and tramadol. Retrospective data were retrieved from the laboratory information system in a national reference laboratory. Drug testing was performed using four mass spectrometry methods that were validated for clinical use. For urine specimens, the positivity rate was the highest for methylphenidate (62.3%, n = 2,489), followed by tramadol (43.7%, n = 3,483), fentanyl (41.9%, n = 4,657), tapentadol (37.9%, n = 736) and meperidine (8.3%, n = 138). Among positive samples, both parent drug and metabolite(s) was detectable in 94.9% of meperidine samples, 94.5% of tramadol samples, 93.8% of fentanyl samples, 89.9% of methylphenidate and 86.6% of tapentadol samples. For serum or plasma specimens, the positivity rate was the highest for tapentadol (75.0%, n = 39), followed by methylphenidate (74.2%, n = 569), fentanyl (53.6%, n = 113), meperidine (41.9%, n = 18) and tramadol (28.9%, n = 213). Similar metabolic patterns were found in serum or plasma. Of positive results, both parent drug and metabolite(s) were found in 94.7% of fentanyl samples, 83.3% of meperidine samples, 79.6% of methylphenidate samples, 53.8% of tapentadol samples and 44.1% of tramadol samples. Our data demonstrates the metabolic patterns of five drugs from a random urine or serum/plasma collection in patients that have been prescribed these medications. The data presented can be used to guide clinicians in determining drug adherence by assessing the positivity rates of the parent drug and corresponding metabolite(s). [ABSTRACT FROM AUTHOR]

Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at -20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range. [ABSTRACT FROM AUTHOR]

Nanotechnology produces a wide range of medicinal compounds, including nanoparticulate silver, which are increasingly introduced in various forms for consumer use. As with all medicinal compounds, potential drug interactions are an important consideration for ingested silver nanoparticles. Nanoparticulate silver–drug interactions may be mediated through induced oxidative stress in liver tissue where the majority of systemically bioavailable silver nanoparticles is found. To investigate whether an orally ingested commercially available colloidal silver nanoproduct produces pharmacokinetic interference on select cytochrome P450 enzymes, a prospective, single-blind, controlledin vivohuman study using simultaneous administration of standardized probes for P450 enzyme classes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a commercial colloidal silver nanoproduct produces detectable silver in human serum after 14 days of dosing. This silver, however, elicits no demonstrable clinically significant changes in metabolic, hematologic, urinary, physical findings or cytochrome P450 enzyme inhibition or induction activity. Given their increasingly broad, diverse human exposures, future characterization of human cytochrome P450 enzyme activity for other systemically bioavailable nanotechnology products are warranted. [ABSTRACT FROM PUBLISHER]

The article reports on the dynamics of the chemical process involve in the analysis of naltrexone and its primary metabolite 6B-naltrexol. According to the author, the process is regarded as a specific and sensitive method used in the analysis of subnanogram-per-milliliter concentrations of the analytes which could be found in rabbit, rat, and human plasma. Moreover, the process was developed using liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The process used in the extraction of plasma samples is the liquid-liquid extraction technique.

Explains metabolism of buprenorphine at therapeutic concentrations in the liver microsomes. Methods adopted to involve utilization of buprenorphine; Role of cytochrome P450 3A4 in the metabolism of buprenorphine.

Examines the effectiveness of the of skin cleansing procedures used prior to application of the PharmChek sweat patch used for drug testing in criminal justice settings. Details of the methodology adopted for the study; Investigation of susceptibility of the patch to contamination from vaporized drugs; Functions of the polyurethane membrane of the sweat patch.

The article presents analytical toxicology research which describes an analysis of anabolic steroids and antiestrogens using a liquid chromatography-tandem mass spectrometry (LS-MS-MS) via quadrupole-time-of-flight (Q-TOF)-based method. The method combines high ionization efficiency and moderate resolving power.

Focuses on the use of antibiotic ofloxacin as a reference marker in hair of various colors and evaluates the efficacy of a reliable marker substance to human subjects in identifying drug use and treatment compliance in drug treatment programs. Benefits of hair analysis in monitoring compliance and recidivism in drug treatment programs; Overview of analytical procedures used in this evaluation; Account of ofloxacin and eumelanin in human hair of various colors.

Haloperidol, fluphenazine, perphenazine, and thiothixene are "typical" antipsychotic drugs that are used in the treatment of schizophrenia and other psychiatric disorders. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with deuterated analog of imipramine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix-matched calibration curve is used for quantitation.

Carisoprodol and meprobamate are centrally acting muscle relaxant/anxiolytic drugs that can exist in a parent-metabolite relationship (carisoprodol → meprobamate) or as a separate pharmaceutical preparation (meprobamate aka Equanil, others). The monitoring of the use of these drugs has both clinical and forensic applications in pain management applications and in overdose situations. LC-MS/MS is used to analyze urine or plasma/serum extracts with deuterated analogs of each analyte as internal standards to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix-matched calibration curve is used for quantitation.

Flecainide, mexiletine, propafenone, and amiodarone are antiarrhythmic drugs that are used primarily in the treatment of cardiac arrhythmias. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with loxapine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix matched calibration curve is used for quantitation.

Ethyl glucuronide and ethyl sulfate are minor conjugated metabolites of ethanol that can be detected in urine for several days after last ingestion of ethanol. The monitoring of ethanol use has both clinical and forensic applications and a longer detection window afforded by monitoring these metabolites is obvious. LC-MS/MS is used to analyze diluted urine with deuterated analogs of each analyte as internal standards to ensure accurate quantitation and control for any potential matrix effects. High aqueous HPLC is used to chromatograph the metabolites. Negative ion electrospray is used to introduce the metabolites into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each metabolite, while a matrix-matched calibration curve is used for quantitation.

To mitigate and circumvent orthopaedic-associated infection, systematic oral and parenteral antibiotic therapy is often used; however, efficacy is limited due to dosing, systemic side-effects, patient compliance, effective delivery, treatment length, and resistant bacteria. A more effective method may be sustained local drug delivery of antibiotics at the wound site, using delivery vehicles that control release rates. In the case of bone for example, this could be clinically familiar bone graft. Unfortunately, without a rate-control strategy, local antibiotic delivery from allograft displays a prominent burst release: a large amount of drug payload is released as a bolus within 72 hours and depleted. Although his offers effective immediate killing, persitor bacteria remain an infection risk. Notably, drug resistance is a problem at reduced antibiotic levels. To allow better local dosing modulation, a degradable polycaprolactone (PCL) polymer allograft coating is used to modulate local delivery of the antibiotic, tobramycin. This polymer/antibiotic hybrid coats the porous structure of the cancellous bone graft, providing a substantial drug reservoir and allowing controlled release of antibiotic over extended time. PCL/tobramycin-coated bone fragments of different PCL molecular weights and variable drug loads are assayed in vitro for drug release. Tobramycin concentration is determined based on derivatization of its 5 primary amine groups with a fluorescent reagent, phthaldialdehyde (OPA). Tobramycin concentrations in release media can be calculated based on a standard curve with a reasonable accuracy and dynamic range.

l-Alpha-acetylmethadol (LAAM) is an alternative to methadone for the maintenance treatment of opioid dependence. LAAM has a longer therapeutic half-life than methadone, primarily because it is metabolized to more active metabolites, norLAAM and dinorLAAM. We have developed a liquid chromatography-tandem mass spectrometry method capable of measuring LAAM and its metabolites, norLAAM and dinorLAAM, at lower concentrations with 1.0-mL aliquots of plasma (range of 0.25 to 100 ng/mL) or higher concentration with 0.2-mL aliquots of plasma (range 1.25 to 500 ng/mL). It has acceptable precision and accuracy across both linear ranges, as well as in the urine matrix. Results from this assay correlate well with our previously validated gas chromatograghy-mass spectrometry method. All analytes had acceptable stability after three freeze-thaw cycles, room temperature storage for 20 h, or storage of extracts either at -20 degrees C for 6 days or on the autosampler (10 degrees C) for 4 days. The pharmacokinetics of LAAM, norLAAM, and dinorLAAM were determined for the first time in three male opioid-naive individuals receiving a single oral dose of 5 mg LAAM/70 kg. Using this method, we could monitor the in vitro N-demethylation of LAAM and norLAAM at substrate concentrations in the therapeutic range of 0.5 and 1.0 microM by cDNA-expressed cytochrome P450s. This confirmed the involvement of cytochrome P450s 3A4, 2B6, 2C8, and 2C18 at therapeutic concentrations of LAAM. An accurate and precise method for determination of LAAM and its metabolites, norLAAM and dinorLAAM, that is suitable for both in vivo and in vitro metabolism studies has been developed and validated., (Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association)

This report describes a sensitive and specific high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for the detection of subnanogram concentrations of selegiline and its three principle metabolites, N-desmethylselegiline, methamphetamine, and amphetamine, in human plasma. The assay has a dynamic range of 0.1-20 ng/mL for selegiline and N-desmethylselegiline (norselegiline) and 0.2-20 ng/mL for methamphetamine and amphetamine. The inter- and intra-assay precision and accuracy varied by less than 11% for all analytes at 0.3, 2.5, and 15 ng/mL and less than 16% at the lower limit of quantitation (0.1 ng/mL for selegiline and norselegiline; and 0.2 ng/mL for methamphetamine and amphetamine). Selegiline and its metabolites showed no significant loss in quantitative accuracy after three freeze/thaw cycles or after up to 6 h at room temperature prior to extraction. Extracted plasma samples retained quantitative accuracy after storage for at least 7 days at -20 degrees C or up to 70 h at room temperature. Methanolic stock solutions were stable for at least 6 h when kept at room temperature or at least 90 days when kept at -20 degrees C.