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A novel miniaturized, solid-contact potentiometric screen-printed electrode was developed for highly sensitive and selective determination of lidocaine anesthetic. The electrode integrated single-walled carbon nanotubes as a solid-contact material and a molecularly imprinted polymer as a recognition sensory material. The performance characteristics of the electrode were evaluated and optimized to display a Nernstian slope of 58.92 ± 0.98 mV/decade over a linear concentration range of 4.53 × 10 -7 to 6.18 × 10 -3  mol/l within < 6 s. The detection limit was 7.75 × 10 -8  mol/l (18.16 ng/ml) of lidocaine. The use of the molecularly imprinted polymer significantly enhanced the selectivity of the electrode, and carbon nanotubes increased the sensitivity, accuracy, and potential stability. The electrode was successfully used for determining lidocaine in pharmaceutical preparations and human urine. The results favorably compared with data obtained by liquid chromatography-tandem mass spectrometry., Competing Interests: Declarations Ethics approval All the experiments adhered to the guidelines set forth in the Declaration of Helsinki (1964) and the Clinical Medical Research Regulation Act of 2020. Approval was granted by the Ethical Committee (EC) of the Faculty of Science, Ain Shams University, Cairo, Egypt. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In this study, bupivacaine (BUP) and meloxicam (MLX) were simultaneously assayed in their co-formulated ampoules without interference using four affordable, sensitive, and eco-friendly spectrophotometric methods. The assay of MLX at 359.3 nm over the concentration range of 1.0-15.0 µg/mL was accomplished using a direct UV-spectrophotometric method (Method I) without interference from BUP. However, there was a significant overlap between the spectra of BUP and MLX, making it difficult to determine BUP directly from the UV spectrum. Therefore, various UV-based techniques, including second derivative spectrophotometry (Method II), ratio subtraction method (Method III), and absorption factor method (Method IV), were used to determine BUP over the concentration range of 5.0-80.0 µg/mL. The proposed methods could simultaneously determine the studied drugs with a challenging ratio of 33.3:1.0 (BUP: MLX), which increases the importance of the current study. The proposed methods were applied to estimate the studied drugs in commercial ampoules with high % recoveries and low %RSD values. The excellent eco-friendliness of the developed methods was demonstrated using GAPI and AGREE metrics. The developed methods were validated according to ICHQ2(R2) guidelines. The proposed methods can be better suited for the routine analysis of BUP and MLX in their fixed-dose combination with high selectivity., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In this study, a new potentiometric sensor was developed for the determination of the local anesthetic drug procaine in pharmaceutical samples. Procaine (Pr)-Tetraphenlyborate (TPB) ion-pair was synthesized and used as a sensor material. Potentiometric sensors using the synthesized ion pair (Pr-TPB), poly(vinyl chloride) (PVC) and o-nitrophenyloctyl ether (o-NPOE) in different proportions were prepared and their performance properties were tested. Among the prepared sensors, the best potentiometric response characteristics were obtained with the sensor composition Pr-TPB:PVC:o-NPOE in the ratio of 6.0:32.0:62.0 (w/w %). The new procaine sensor developed in the present study had a near-Nernstian behavior of 54.1 ± 3.3 mV/per decade and a low detection limit of 3.18 × 10 -5  mol L -1 in the concentration range of 1.0 × 10 -1 -1.0 × 10 -4  mol L -1 . Additionally, the sensor had a response time of less than 10 s and could work in a wide pH range for two different concentration values without being affected by pH changes. Finally, the new procaine potentiometric sensor was used to detect procaine in injection samples and successfully determined procaine concentrations with high recoveries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A gradient elution high-performance liquid chromatographic method with a diode array detector is introduced for the first time for the simultaneous estimation of three drugs, namely, oxytetracycline hydrochloride (OXT), lidocaine (LDC), and bromhexine hydrochloride (BRH), in a veterinary formulation (OxyClear® solution) that contains many interfering additives. The method used a C-8 column. The chromatographic eluting solution included acidified water (0.1% trifluoroacetic acid in water) and acetonitrile at a 1-ml/min flow rate and 254 nm as a nominated detection wavelength. The chromatographic process was assessed in terms of linearity, precision, accuracy, LOD, and LOQ. OXT, LDC, and BRH were linear in the range of 1-60, 5-100, and 1-60 μg/ml, respectively. The three drugs were determined successfully without the interference of three excipients having UV absorbances. Furthermore, the purities of the peaks of the three drugs were confirmed by comparing the UV spectra of investigated peaks to the UV reference spectra in Clarke's Analysis of Drugs and Poisons. The greenness value of the method was 0.69 with a faint green-colored pictogram using the AGREE tool. These merits recommend the application of the planned method in QC laboratories for purity testing and concentration assays for the pure drugs and commercial formulations., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Local anesthetics (LAs) are widely used in anesthesiology, ophthalmology, and otolaryngology as well as for treatment of chronic and oncological pain. However, anesthetics can cause adverse effects up to lethal ones. In this work, we cited reviews on chromatographic and spectroscopic methods of local anesthetics determination published earlier, and the main purpose was to review the possibilities and advantages of voltammetric methods used for the LAs determination. The electrochemical behavior, mechanism of LAs transformation on the various working electrodes and analytical parameters of voltammetric methods used for their determination were reviewed in the work. Vast majority of these methods were developed for the most widely used anesthetics in medicine like benzocaine, lidocaine and procaine. Special attention was paid to possible mechanisms of electrochemical oxidation and in some cases reduction of LAs or their derivatives. Voltammetry is used for the determination of LAs in pharmaceutical formulations and in biological fluids. The analytical characteristics in terms of sensitivity, selectivity, reproducibility also were discussed in the article.

Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade of the voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in a liquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions: articaine, 285→8658 m/z; mepivacaine, 247→9870 m/z; lidocaine - internal standard -, 235→8658 m/z). The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of 0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. The new procedure was also successfully applied to a preliminary pharmacokinetics study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To evaluate the sterility of bupivacaine liposome injectable suspension (Nocita®) used in a multiple-dose fashion for 5 days., Study Design: Triplicate liposomal bupivacaine vials were stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). A 3-mL aliquot was withdrawn from each vial daily. Samples were inoculated in tryptic soy broth in triplicate and then incubated for 24 hours at 37°C and subcultured every 48 hours onto blood agar and Sabouraud dextrose agar, respectively. Separate 1.5-mL aliquots of liposomal bupivacaine were centrifuged at 3500 g to separate liposome-encapsulated bupivacaine from the solution. Concentration of unencapsulated bupivacaine was analyzed via high-pressure liquid chromatography. Data were analyzed by using mixed effects procedure with multiple comparisons., Sample Population: Ten 20-mL vials of bupivacaine liposome injectable suspension stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C)., Results: Five days of repeated withdrawal from the single-use vials yielded no bacterial growth. One control vial, which was opened and punctured once on the last day of the experiment, yielded fungal growth of an Aspergillus spp, likely an environmental contaminant. The concentration of free bupivacaine did not significantly differ until the fifth day of sampling., Conclusion: When aseptic technique was used, liposomal bupivacaine remained sterile for 5 days. Concentrations of free bupivacaine were unchanged from baseline for 4 days in both refrigerated and room temperature conditions., Clinical Significance: Single-use liposomal bupivacaine vials can be used extralabel in a multiple-dose fashion for up to 4 days when stored either refrigerated or room temperature when sterile technique is used., (© 2020 The American College of Veterinary Surgeons.)

Purpose: Lidocaine (LID) is a local anesthetic that is administered either by injection and/or a topical/transdermal route. However, there is a current need to develop efficacious methods for the oral delivery of LID with optimized bioavailability., Methods: We developed oral LID biodegradable microspheres that were loaded with alginate-chitosan with different mass ratios, and characterized these microspheres in vitro. We also developed, and utilized, a simple and sensitive HPLC-tandem mass spectrometry (LC-MS-MS) method for assaying LID microspheres., Results: The mean particle size (MPS) of the LID microspheres ranged from 340.7 to 528.3 nm. As the concentration of alginate was reduced, there was a significant reduction in MPS. However, there was no significant change in drug entrapment efficiency (DEE), or drug yield, when the alginate concentration was either increased or decreased. DSC measurements demonstrated the successful loading of LID to the new formulations. After a slow initial release, less than 10% of the LID was released in vitro within 4 h at pH 1.2. In order to evaluate nephrotoxicity, we carried out MTT assays of LID in two types of cell line (LLC-PK1 and MDCK). LID significantly suppressed the cell toxicity of both cell lines at the concentrations tested (100, 200, and 400ng/µL)., Conclusion: Experiments involving the oral delivery of LID formulations showed a significant reduction in particle size and an improvement in dissolution rate. The formulations of LID developed exhibit significantly less toxicity than LID alone., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 ALQuadeib et al.)

We report the on-line coupling of a monolithic molecularly imprinted polymer to nano-liquid chromatography for the selective analysis of cocaine and its main metabolite, benzoylecgonine, in complex biological samples. After the screening of different synthesis conditions, a monolithic molecularly imprinted polymer was in situ synthesized into a 100 μm internal diameter fused-silica capillary using cocaine as template, methacrylic acid as functional monomer, and trimethylolpropane trimethacrylate as cross-linker. Scanning electron microscopy was used to assess the homogeneous morphology of the molecularly imprinted polymer and its permeability was measured. Its selectivity was evaluated by nano-liquid chromatography-ultraviolet, leading to imprinting factors of 3.2 ± 0.5 and 2.2 ± 0.3 for cocaine and benzoylecgonine, respectively, on polymers resulting from three independent syntheses, showing the high selectivity and the repeatability of the synthesis. After optimizing the extraction protocol to promote selectivity, the monolithic molecularly imprinted polymer was successfully on-line coupled with nano-liquid chromatography-ultraviolet for the direct extraction and analysis of cocaine present in spiked human plasma and saliva samples. The repeatability of the obtained extraction recovery, between 85.4 and 98.7% for a plasma sample spiked at 100 ng mL -1 , was high with relative standard deviation values lower than 5.8% for triplicate analyses on each of the three independently synthesized molecularly imprinted polymers. A linear calibration range was achieved between 100 and 2000 ng mL -1  (R 2  = 0.999). Limits of quantification of 14.5 ng mL -1 and 6.1 ng mL -1 were achieved in plasma and urine samples, respectively. The very clean-baseline of the resulting chromatogram illustrated the high selectivity brought by the monolithic molecularly imprinted polymer that allows the removal of a huge peak corresponding to the elution of interfering compounds and the easy determination of the target analyte in these complex biological samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The effectiveness of decontamination procedures used for the removal of external drug contamination in forensic hair analysis is an ongoing debate. This investigation evaluated wash methods complying with Society of Hair Testing (SoHT) guidelines and their capacity to remove cocaine (COC) and methamphetamine (MA) from artificially contaminated hair. The most effective decontamination method was determined using a systematic approach, involving (1) an initial washing solvent screen, (2) optimization of wash duration, (3) comparison of sequential wash methods, and (4) reanalysis of clinical hair samples. For analysis, hair was subjected to micro-pulverized methanolic extraction prior to quantitation by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Methanol (MeOH) and 0.1 M phosphate buffer (pH 6) were the most effective organic and aqueous solvents, respectively, removing 28%-38% of COC and 16%-31% of MA. Wash durations longer than 30-60 minutes did not remove additional amounts, and a more efficient sequential wash method was subsequently developed. Despite this, the interpretation of reportable results relative to the SoHT cut-off levels was unchanged for most clinical hair samples reanalyzed after washing by agitation for 30 minutes with MeOH. These findings highlight the inability of decontamination solvents to completely remove external COC and MA contamination from hair, including wash methods adhering to SoHT guidelines., (© 2019 John Wiley & Sons, Ltd.)

Today, rape and sexual assault cases are mainly solved using evidence such as medical evidence or DNA analysis. Condom traces have been found to be present in 10% of assaulted women, when no DNA is found [1]. Numerous studies have emphasized the interest of analysing the composition of male condoms and their traces, and developing specific methods for the analysis of this type of evidence. However, transfer and persistence of condom traces in a specific matrix are rarely referenced. Therefore, forensic scientists have no complete knowledge of the trace and what could be expected in a real case. The purpose of this article is to review the literature addressing the composition of condoms and their traces as well as its influence on the transfer and persistence from a forensic point of view. Peer-reviewed literature, patents, professional literature, data from international administrations and international organisations' reports have been used to track the composition and the problematics of transfer and persistence of condom traces. The results of this review show that the composition of male condoms and their traces are complex systems, with numerous compounds originating from the condom at the moment of the transfer and evolving over time according to specific persistence patterns. Although numerous types of analyses have already been proposed and tested for condom traces, forensic evidence considerations have not been fully studied yet. Considering the fact that sexual assaults without the detection of DNA are increasingly frequent, there is a definite medical and forensic need to improve our knowledge of the processes involved in the development of condom traces in order to better understand analytical results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

During investigations of unnatural death, the time of death is generally estimated using anatomical examinations. However, it can be difficult to accurately determine the day of death, because postmortem changes in the body tissues can be greatly affected by the circumstances of the location of the corpse. We recently developed a method to estimate the day of drug ingestion, using micro-segmental hair analysis based on internal temporal markers (ITMs). In this method, ITMs are ingested at a specific time interval before hair collection to mark timescales within individual hair strands. A single hair strand is segmented at 0.4-mm intervals, corresponding to average daily hair growth. The day of drug ingestion is eventually estimated by calculating the distances between segments containing the drug and ITMs in a hair strand. In the present study, the method was applied to estimate the day of death. A corpse was discovered with a documented medical history of lidocaine administration for surgery 57 days before the discovery. Micro-segmental analysis of a hair plucked from the corpse was performed using lidocaine as an ITM. Lidocaine was detected at specific regions in the hair strands. The day of death was estimated using the known surgery day, the distance from the hair root to the lidocaine peak in the hair strand, and the average hair growth rate. The novel estimation method using a hair enabled us to narrow the estimated time range of death up to the day of death, unlike the conventional anatomical examination. The micro-segmental hair analysis based on drug use history can be extremely helpful in determining the time of an unnatural death.

Background: The work presented here is focused on the development of a comprehensive theoretical model for the description of drug release from a double - layer bioresorbable suture thread and the therapeutic efficacy of the active compounds delivered in the surrounding tissue., Methods: In particular, the system under investigation is composed of a core of slow-degrading polylactic- acid-co-ε-caprolactone (PLCL), where an antibiotic compound (Vancomycin) is loaded, surrounded by a shell of a fast-degrading polylactic-co-glycolic acid (PLGA) which contains an anesthetic drug (Lidocaine hydrochloride) for the post-surgical pain relief., Results: This system is of potential interest for the combined effects provided by the different active molecules, but the different release and polymer degradation dynamics, as well as their mutual influence, do not allow an intuitive a priori evaluation of device behavior, which can be rationalized through mathematical modeling. The model takes into account the main involved phenomena (polymer degradation and diffusion of the drugs within the device and the tissue, where they are metabolized) and their synergic effects on the overall system behavior., Conclusion: Model results are discussed in order to quantify the impact of the main design parameters on device performances, thanks to the use of phase diagrams (which show drug effect in time and space) whose insights are summarized in order to determine a design space according to the specific needs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Herein, reduced graphene oxide (RGO) has been utilized as an efficient sorbent in microextraction by packed sorbent (MEPS). The combination of MEPS and liquid chromatography-tandem mass spectrometry has been used to develop a method for the extraction and determination of three local anesthetics (i.e. lidocaine, prilocaine, and ropivacaine) in human plasma and saliva samples. The results showed that the utilization of RGO in MEPS could minimize the matrix effect so that no interfering peaks at the retention times of the analytes or internal standard was observed. The high extraction efficiency of this method was approved by mean recoveries of 97.26-106.83% and 95.21-105.83% for the studied analytes in plasma and saliva samples, respectively. Intra- and inter-day accuracies and precisions for all analytes were in good accordance with the international regulations. The accuracy values (as percentage deviation from the nominal value) of the quality control samples were between -2.1 to 13.9 for lidocaine, -4.2 to 11.0 for prilocaine and between -4.5 to -2.4 for ropivacaine in plasma samples while the values were ranged from -4.6 to 1.6 for lidocaine, from -4.2 to 15.5 for prilocaine and from -3.3 to -2.3 for ropivacaine in human saliva samples. Lower and upper limit of quantification (LLOQ, ULOQ) were set at 5 and 2000 nmol L -1 for all of the studied drugs. The correlation coefficients values were ≥0.995. The limit of detection values were obtained 4 nmol L -1 for lidocaine and prilocaine, and 2 nmol L -1 for ropivacaine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Seized samples of illegally produced cocaine have a very large variability in composition; a fact that may result in a challenge to their analysis. We demonstrate here a simple and fast method to detect the presence of cocaine in both hydrochloride and free-base forms in illicit drug samples by nuclear magnetic resonance (NMR) spectroscopy. This is achieved by combining the commonly used 1D spectra and diffusion-ordered spectroscopy and introducing the 2D maximum-quantum NMR approach to forensic analysis. The protocol allows the facile determination of the cocaine forms even in the presence of multiple adulterants. By relying on non-uniform sampling acceleration of 2D spectroscopy, the identification can be obtained in less than 3 min for 10 mg of product. Moreover, we show that intermolecular interactions of the sample constituents, while affecting the analysis result, do not interfere with the quality of the detection of the proposed protocol.

Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i.e., chemical integrity) of the adulterants heated. To achieve this goal, the following strategies were applied: (1) a CP adulterated sample was heated and its fume was chemically analyzed; (2) the vapor of isolated adulterants were analyzed after heating; (3) plasma levels of animals exposed to CP and adulterants were measured. Ninety percent of CP seized samples were adulterated. Adulteration was dominated by phenacetin and caffeine and much less by other compounds (i.e., aminopyrine, levamisole, benzocaine). In the majority of CP analyzed samples, both cocaine and caffeine content was 30%, phenacetin 20% and the combination of these three components reached 90%. Typical cocaine pyrolysis compounds (i.e., BA, CMCHTs, and AEME) were observed in the volatilized cocaine and CP sample but no pyrolysis compounds were found after isolated adulterants heating. Cocaine, phenacetin, and caffeine were detected in plasma. We provide current forensic data about CP seized samples and demonstrated the chemical integrity of their adulterants heated.

Traditionally, fast screening for the presence of cocaine in unknown powders is performed by means of colour tests. The major drawbacks of these tests are subjective colour evaluation depending on the operator ('50 shades of blue') and a lack of selectivity. An alternative fast screening technique is Fourier Transform InfraRed (FTIR) spectrometry. This technique provides spectra that are difficult to interpret without specialized expertise and shows a lack of sensitivity for the detection of cocaine in mixtures. To overcome these limitations, a portable FTIR spectrometer using Attenuated Total Reflectance (ATR) sampling was combined with a multivariate technique, called Support Vector Machines (SVM). Representative street drug powders (n = 482), seized during the period January 2013 to July 2015, and reference powders (n = 33) were used to build and validate a classification model (n = 515) and a quantification model (n = 378). Both models were compared with the conventional chromatographic techniques. The SVM classification model showed a high sensitivity, specificity, and efficiency (99%). The SVM quantification model determined cocaine content with a root mean squared error of prediction (RMSEP) of 6% calculated over a wide working range from 4 to 99 w%. In conclusion, the developed models resulted in a clear output (cocaine detected or cocaine not detected) and a reliable estimation of the cocaine content in a wide variety of mixtures. The ATR-FTIR technique combined with SVM is a straightforward, user-friendly, and fast approach for routine classification and quantification of cocaine in seized powders. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

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., (Copyright © 2016 John Wiley & Sons, Ltd.)

Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Since potential changes in the dynamics and mobility of drugs upon complexation for delivery may affect their ultimate efficacy, we have investigated the dynamics of two local anesthetic molecules, bupivacaine (BVC, C 18 H 28 N 2 O) and ropivacaine (RVC, C 17 H 26 N 2 O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The study was carried out by neutron scattering spectroscopy, along with thermal analysis, and density functional theory computation. Mean square displacements suggest that RVC may be less flexible in crystalline form than BVC, but both molecules exhibit very similar dynamics when confined in HP-β-CD. The use of vibrational analysis by density functional theory (DFT) made possible the identification of molecular modes that are most affected in both molecules by insertion into HP-β-CD, namely those of the piperidine rings and methyl groups. Nonetheless, the somewhat greater structure in the vibrational spectrum at room temperature of complexed RVC than that of BVC, suggests that the effects of complexation are more severe for the latter. This unique approach to the molecular level study of encapsulated drugs should lead to deeper understanding of their mobility and the respective release dynamics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Third-hand smoke is the residue remaining on surfaces during smoking events. It is composed of particles and vapours that form upon heating. The phrase 'third-hand smoke' is primarily used to describe nicotine and other chemicals from cigarettes, but any residues formed from the smoking of various substances could be classified similarly. There has been an increasing body of research on third-hand smoke from cigarettes in the last decade, but little has been done in regards to understanding the persistence of particles and vapours from illicit drugs. In this work, small samples of cocaine and methamphetamine were volatilized to produce an illicit drug smoke that was collected onto various surface materials and left exposed to ambient conditions over 672 h (four weeks). Chemical analyses by electrospray ionization-mass spectrometry of residues on silicon, plastic, laminate, and artificial leather surfaces indicated a rapid decrease in recovery of the parent molecule, with varied formation of decomposition products over the first 168 h of exposure. Measurable amounts of the parent molecule were still present after 672 h, exhibiting a strong persistence of these drugs on various household materials. This is important in a forensic science context, as third-hand smoke residues could provide a viable source of trace evidence previously not utilized. Published 2016. This article is a U.S. Government work and is in the public domain in the USA., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Five different chemometric methods were developed for the simultaneous determination of betamethasone dipropionate (BMD), clotrimazole (CT) and benzyl alcohol (BA) in their combined dosage form (Lotriderm® cream). The applied methods included three full spectrum based chemometric techniques; namely principal component regression (PCR), Partial Least Squares (PLS) and Artificial Neural Networks (ANN), while the other two methods were PLS and ANN preceded by genetic algorithm procedure (GA-PLS and GA-ANN) as a wavelength selection procedure. A multilevel multifactor experimental design was adopted for proper construction of the models. A validation set composed of 12 mixtures containing different ratios of the three analytes was used to evaluate the predictive power of the suggested models. All the proposed methods except ANN, were successfully applied for the analysis of their pharmaceutical formulation (Lotriderm® cream). Results demonstrated the efficiency of the four methods as quantitative tool for analysis of the three analytes without prior separation procedures and without any interference from the co-formulated excipient. Additionally, the work highlighted the effect of GA on increasing the predictive power of PLS and ANN models., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, a new method has been developed for the simple determination of mepivacaine (carbocaine). The method is based on the enhancement effect of mepivacaine in the chemiluminescence (CL) reaction of tris(1,10 phenanthroline) ruthenium(II) with cerium(IV). A mechanism for the CL reaction has been proposed on the basis of UV-Vis, fluorescent and CL spectra. Under optimum conditions, the CL intensity was proportional to the concentration of the drug in solution over the range 0.45-226.25 μg mL-1 (R2 = 0.9996). The LOD was 0.34 μg mL-1 (S/N = 3). LOD was about 10 times lower than the therapeutic concentration of mepivacaine. The percent of relative standard deviation for determination of 11 replicates at level of 9.05 μg mL-1 and 90.50 μg mL-1 of mepivacaine were 1.8 and 3.7%, respectively. The proposed method was applied successfully for the determination of mepivacaine in human plasma and injectable solutions.

A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10 -8 M (4.5-13 ng/mL), with the borate capping agent having the best performance.

Drug analysis represents a large field in different disciplines. Plasma is commonly considered to be the biosample of choice for that purpose. However, concentrations often do not represent the levels present within deeper compartments and therefore cannot sufficiently explain efficacy or toxicology of drugs. MALDI-MS in drug analysis is of great interest for high-throughput quantification and particularly spatially resolved tissue imaging. The current perspective article will deal with challenges and opportunities of MALDI-MS drug analysis in different biological samples. A particular focus will be on hair samples. Recent applications were included, reviewed for their instrumental setup and sample preparation and pros and cons as well as future perspectives are critically discussed.

A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.

In a prospective sample of 80 mother-infant dyads, we investigated whether drugs of abuse in maternal hair measured during the pregnancy trimesters were also present in neonatal meconium. Principal drugs of abuse were analyzed in the three consecutive maternal hair segments and meconium samples by ultra-performance liquid chromatography tandem mass spectrometry assay. Of the 80 mothers, 32 (40%) presented one or more hair shafts with at least one of the analyzed drugs of abuse and/or its metabolites. The drug of abuse with a higher prevalence in our study population was methamphetamine: 19 mothers had methamphetamine in one or more hair segments (59.4%). The second most detected drug of abuse was cocaine; nine mothers presented cocaine in one or more hair segments (28.1%). Nineteen pregnant women consumed at least one drug of abuse during the first trimester, ten continued consuming drugs of abuse during the second trimester; and nine consumed until the end of pregnancy. Five of the nine newborns from mothers who consumed drugs during the whole pregnancy showed drugs of abuse in meconium samples. Newborns from the 23 remaining mothers with one or two hair shafts positive to drugs of abuse did not present drugs in their meconium. Indeed from these results, it seems that discontinuous and/or sporadic consumption during pregnancy could produce a negligible transplacental passage and hence negative results in meconium. Furthermore, the role of placenta in the metabolism and excretion of drugs of abuse is still to be precisely investigated. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

The occurrence and prognosis of many complex diseases, such as cancers, is associated with the variation of various molecules, including DNA at the genetic level, RNA at the regulatory level, proteins at the functional level and small molecules at the metabolic level (defined collectively as multilevel molecules). Thus it is highly desirable to develop a single platform for detecting multilevel biomarkers for early-stage diagnosis. Here we report a protocol on DNA-nanostructure-based programmable engineering of the biomolecular recognition interface, which provides a universal electrochemical biosensing platform for the ultrasensitive detection of nucleic acids (DNA/RNA), proteins, small molecules and whole cells. The protocol starts with the synthesis of a series of differentially sized, self-assembled tetrahedral DNA nanostructures (TDNs) with site-specifically modified thiol groups that can be readily anchored on the surface of a gold electrode with high reproducibility. By exploiting the rigid structure, nanoscale addressability and versatile functionality of TDNs, one can tailor the type of biomolecular probes appended on individual TDNs for the detection of specific molecules of interest. Target binding occurring on the gold surface patterned with TDNs is quantitatively translated into electrochemical signals via a coupled enzyme-based catalytic process. This uses a sandwich assay strategy in which biotinylated reporter probes recognize TDN-bound target biomolecules, which then allow binding of horseradish-peroxidase-conjugated avidin (avidin-HRP). Hydrogen peroxide (H2O2) is then reduced by avidin-HRP in the presence of TMB (3,3',5,5'-tetramethylbenzidine) to generate a quantitative electrochemical signal. The time range for the entire protocol is ∼1 d, whereas the detection process takes ∼30 min to 3 h.

A simple, isocratic, high-resolution and prompt HPLC-PDA method was developed and validated for the simultaneous quantification of prilocaine (PCL) and lidocaine (LCL) hydrochlorides in in vitro buccal iontophoresis-driven permeation studies. A reversed-phase C18 column (250 mm x 4.6 mm, 3μm, 110Å) was used for the chromatographic separation. The mobile phase contained acetonitrile: 0.1M sodium phosphate buffer, pH 7.0 (1:1, v/v), plus 0.05% (v/v) diethylamine. The isocratic flow rate was set at 1 mL/min and the detection wavelength was 203 nm. PCL and LCL eluted in 8.9 min and 13 min, respectively, and the system suitability parameters varied within an acceptable range. The method was selective, sensitive, precise, accurate and robust, producing a linear plot at the concentration range of 0.25 to 10 µg/mL. The application of this method was demonstrated by a significant enhancement of the permeation of PCL and LCL with the application of iontophoresis (1 mA/cm(2) per 1 h) through isolated porcine esophageal epithelium. The amount of the drug retained in the epithelium also increased with the application of an electrical current. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Quick and presumptive identification of seized drug samples without destroying evidence is necessary for law enforcement officials to control the trafficking and abuse of drugs. This work reports an automated screening method to detect the presence of cocaine in seized samples using portable Fourier transform infrared (FT-IR) spectrometers. The method is based on the identification of well-defined characteristic vibrational frequencies related to the functional group of the cocaine molecule and is fully automated through the use of an expert system. Traditionally, analysts look for key functional group bands in the infrared spectra and characterization of the molecules present is dependent on user interpretation. This implies the need for user expertise, especially in samples that likely are mixtures. As such, this approach is biased and also not suitable for non-experts. The method proposed in this work uses the well-established "center of gravity" peak picking mathematical algorithm and combines it with the conditional reporting feature in MicroLab software to provide an automated method that can be successfully employed by users with varied experience levels. The method reports the confidence level of cocaine present only when a certain number of cocaine related peaks are identified by the automated method. Unlike library search and chemometric methods that are dependent on the library database or the training set samples used to build the calibration model, the proposed method is relatively independent of adulterants and diluents present in the seized mixture. This automated method in combination with a portable FT-IR spectrometer provides law enforcement officials, criminal investigators, or forensic experts a quick field-based prescreening capability for the presence of cocaine in seized drug samples., (© The Author(s) 2016.)

The vasoconstrictive effect due to the addition of epinephrine to local anesthetic has been clearly shown by measuring blood-flow volume or blood anesthetic concentration in oral mucosal tissue. However, there are no reports on the measurement of anesthetic concentration using samples directly taken from the jawbone and oral mucosal tissue. Consequently, in this study, the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine was considered by quantitatively measuring lidocaine concentration within the tissue. Japanese white male rabbits (n = 96) were used as test animals. General anesthesia was induced by sevoflurane and oxygen, and then cannulation to the femoral artery was performed while arterial pressure was constantly recorded. Infiltration anesthesia was achieved by 0.5 mL of 2% lidocaine containing 1 : 80,000 epinephrine in the upper jawbone (E(+)) and 0.5 mL of 2% of epinephrine additive-free lidocaine (E(0)) under the periosteum. At specified time increments (10, 20, 30, 40, 50, and 60 minutes), samples from the jawbone, oral mucosa, and blood were collected, and lidocaine concentration was directly measured by high-performance liquid chromatography. No significant differences in the change in blood pressure were observed either in E(+) or E(0). In both E(+) and E(0) groups, the serum lidocaine concentration peaked 10 minutes after local anesthesia and decreased thereafter. At all time increments, serum lidocaine concentration in E(+) was significantly lower than that in E(0). There were no significant differences in measured lidocaine concentration between jawbone and mucosa within either the E(+) or the E(0) groups at all time points, although the E(0) group had significantly lower jawbone and mucosa concentrations than the E(+) group at all time points when comparing the 2 groups to each other. Addition of epinephrine to the local anesthetic inhibited systemic absorption of local anesthetic into the blood such that a high concentration could be maintained in the tissue. Epinephrine-induced vasoconstrictive effect was observed not only in the oral mucosa but also in the jawbone.

An LC/MS/MS method to identify and quantitate in hair the minor metabolites of cocaine-meta-, para-, and ortho-hydroxy cocaine-was developed and validated. Analysis was performed on a triple quadrupole ABSciex API 3000 MS equipped with an atmospheric pressure ionization source via an IonSpray (ESI). For LC, a series 200 micro binary pump with a Perkin Elmer Model 200 autosampler was used. The limit of detection (LOD) and limit of quantification (LOQ) were 0.02 ng/10 mg hair, with linearity from 0.02 to 10 ng/10 mg hair. Concentrations of the para isomer in extensively washed hair samples were in the range of 1-2 % of the cocaine in the sample, while the concentrations of the ortho form were considerably less. The method was used to analyze large numbers of samples from two populations: workplace and criminal justice. In vitro experiments to determine if deodorants or peroxide-containing cosmetic treatments could result in the presence of these metabolites in hair showed that this does not occur with extensively washed hair. Presence of hydroxycocaines, when detected after aggressive washing of the hair samples, provides a valuable additional indicator of ingestion of cocaine rather than mere environmental exposure.

Paravertebral block (PVB) is the technique of injecting a local anesthetic solution alongside the vertebral column, close to where the spinal nerves emerge, resulting in unilateral somatic and sympathetic nerve blockade. Here is reported a fatal case involving a 60-year-old woman with spondylitis arthropathy, who developed cardiac and respiratory arrest 40min after receiving an accidental subarachnoid injection (L5-S1 bilaterally) of depomedrol lidocaine and levobupivacaine. A complete autopsy including histological and toxicological analyses was performed in order to establish the cause of death. Liquid/liquid extraction (LLE) and GC-MS analysis were performed according to a previously published method. Lidocaine and bupivacaine were detected both in blood, at concentrations of 14.8mg/L and 13.3mg/L respectively, and in cerebrospinal fluid (CSF) at concentrations of 287.1mg/L and 464.2mg/L respectively. Both lidocaine and bupivacaine were also detected in the urine. The toxicological findings along with the autopsy allowed us to establish that the accidental subarachnoid injection of lidocaine and levobupivacaine had led to a progressive hypotension and normovolaemic shock caused by a severe ganglionic block, determining the patient's death., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This paper describes a label-free and real-time piezoelectric aptasensor for the detection of cocaine. The acoustic wave sensing platform is a quartz substrate functionalized with an adlayer of S-(11-trichlorosilyl-undecanyl)-benzenethiosulfonate (BTS) cross-linker onto which the anti-cocaine MN4 DNA aptamer is next immobilized. Preparation of the sensor surface was monitored using X-ray photoelectron spectroscopy (XPS), while the binding of cocaine to surface-attached MN4 was evaluated using the electromagnetic piezoelectric acoustic sensor (EMPAS). The MN4 aptamer, unlike other cocaine aptamer variants, has its secondary structure preformed in the unbound state with only tertiary structure changes occurring during target binding. It is postulated that the highly sensitive EMPAS detected the binding of cocaine through target mass loading coupled to aptamer tertiary structure folding. The sensor achieved an apparent Kd of 45 ± 12 µM, and a limit of detection of 0.9 µM. Repeated regenerability of the sensor platform was also demonstrated. This work constitutes the first application of EMPAS technology in the field of aptasensors. Furthermore, it is so far one of the very few examples of a bulk acoustic wave aptasensor that is able to directly detect the binding interaction between an aptamer and a small molecule in a facile one-step protocol without the use of a complex assay or signal amplification step., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse. IR-MALDESI response to a wide range of lipid classes has been demonstrated, with enhanced lipid coverage received by varying the laser wavelength used for mass spectrometry imaging (MSI). Targeted MS(2) imaging (MS(2)I) of an analyte, cocaine, deposited beneath whole body sections allowed determination of tissue-specific ion response factors, and CID fragments of cocaine were monitored to comment on wavelength-dependent internal energy deposition based on the "survival yield" method.

We report on self-assembled nanocube-based plasmene nanosheets as new surface-enhanced Raman scattering (SERS) substrates toward direct identification of a trace amount of drugs sitting on topologically complex real-world surfaces. The uniform nanocube arrays (superlattices) led to low spatial SERS signal variances (∼2%). Unlike conventional SERS substrates which are based on rigid nanostructured metals, our plasmene nanosheets are mechanically soft and optically semitransparent, enabling conformal attachment to real-world solid surfaces such as banknotes for direct SERS identification of drugs. Our plasmene nanosheets were able to detect benzocaine overdose down to a parts-per-billion (ppb) level with an excellent linear relationship (R(2) > 0.99) between characteristic peak intensity and concentration. On banknote surfaces, a detection limit of ∼0.9 × 10(-6) g/cm(2) benzocaine could be achieved. Furthermore, a few other drugs could also be identified, even in their binary mixtures with our plasmene nanosheets. Our experimental results clearly show that our plasmene sheets represent a new class of unique SERS substrates, potentially serving as a versatile platform for real-world forensic drug identification.

We report a high-throughput chip-based nanoelectrospray ionization method coupled with Fourier transform mass spectrometry to screen for local anesthetics in samples collected by swabbing. These drugs have been used to mask pain on the limbs of walking horses after forbidden practices of soring or physical abuse. Optimized for lidocaine, the method afforded sub-ppm mass accuracy for nine local anesthetics included in the study. From doped cotton swabs, two third and all of the analytes were detected after adding 10 ng and 100 ng of each drug, respectively. Benzocaine and/or lidocaine were found on positive swab samples collected during walking horse competitions., (Copyright © 2015 John Wiley & Sons, Ltd.)

The potential and applicability of UHPSFC-MS/MS for anti-doping screening in urine samples were tested for the first time. For this purpose, a group of 110 doping agents with diverse physicochemical properties was analyzed using two separation techniques, namely UHPLC-MS/MS and UHPSFC-MS/MS in both ESI+ and ESI- modes. The two approaches were compared in terms of selectivity, sensitivity, linearity and matrix effects. As expected, very diverse retentions and selectivities were obtained in UHPLC and UHPSFC, proving a good complementarity of these analytical strategies. In both conditions, acceptable peak shapes and MS detection capabilities were obtained within 7 min analysis time, enabling the application of these two methods for screening purposes. Method sensitivity was found comparable for 46% of tested compounds, while higher sensitivity was observed for 21% of tested compounds in UHPLC-MS/MS and for 32% in UHPSFC-MS/MS. The latter demonstrated a lower susceptibility to matrix effects, which were mostly observed as signal suppression. In the case of UHPLC-MS/MS, more serious matrix effects were observed, leading typically to signal enhancement and the matrix effect was also concentration dependent, i.e., more significant matrix effects occurred at the lowest concentrations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A new ambient ionization method allowing the direct chemical analysis of living human body by mass spectrometry (MS) was developed. This MS method, namely Megavolt Electrostatic Ionization Mass Spectrometry, is based on electrostatic charging of a living individual to megavolt (MV) potential, illicit drugs, and explosives on skin/glove, flammable solvent on cloth/tissue paper, and volatile food substances in breath were readily ionized and detected by a mass spectrometer.

This paper describes the voltammetric determination of cocaine in presence of three different interferences that could be found in street samples using disposable sensors. The electrochemical analysis of this alkaloid can be affected by the presence of codeine, paracetamol or caffeine, whose oxidation peaks may overlap and lead to false positives. This work describes two different solutions to this problem. On one hand, the modification of disposable carbon sensors with carbon nanotubes allows the voltammetric quantification of cocaine by using ordinary least squares regressions in the concentration range from 10 to 155 μmol L(-1), with a reproducibility of 5.6% (RSD, n = 7. On the other hand, partial least squares regressions are used for the resolution of the overlapped voltammetric signals when using screen-printed carbon electrodes without any modification. Both procedures have been successfully applied to the evaluation of the purity of cocaine street samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation.

For the first time, dried saliva spot (DSS) was used as a sampling technique for saliva samples. In the DSS technique 50 μL of saliva was collected on filter paper and the saliva was then extracted with an organic solvent. The local anesthetic lidocaine was used as a model compound, which was determined in the DSS using liquid chromatography and mass spectrometry. The results obtained for the determination of lidocaine in saliva using DSS were compared with those from a previous study using a microextraction by packed sorbent syringe as the sampling method for saliva. This study shows that DSS can be used for the analysis of saliva samples. The method is promising and very easy in terms of sampling and extraction procedures. The results from this study are in good agreement with those from our previous work on the determination of lidocaine in saliva. DSS can open a new dimension in the saliva handling process in terms of sampling, storing and transport., (Copyright © 2014 John Wiley & Sons, Ltd.)

Topically applied tetracaine is a local anaesthetic. A novel HPLC method for the rapid and sensitive analysis of tetracaine was developed and compared with a short end direction capillary zone electrophoresis (CZE) method. The method was developed and validated for the separation and quantification of tetracaine in skin samples removed by 'tape-stripping'. Tetracaine was extracted from tape with 100% methanol, which was then diluted to 50% with water for injection. Tetracaine and the internal standard, procaine, were separated on a reversed-phase Luna PFP(2), 3 µm, 150 × 4.6 mm column at ambient temperature using isocratic elution with KH2 PO4 buffer (pH 2.5) and methanol (35:65, v/v). The flow rate was 1 mL/min, with detection at 312 nm. The limit of quantification for tetracaine was 0.03 µg/mL. Calibration lines were linear with r(2) values >0.99. The within- and between-assay imprecision and the percentage of inaccuracy for the QC samples including lower and upper limits of quantitation were <6 and <10%. The absolute mean recovery of tetracaine was >92%. Compared with CZE, the mean percentage error and the absolute mean percentage error were 0.62 and 6.29, respectively. The two methods were compared in a number of pharmacokinetic studies., (Copyright © 2014 John Wiley & Sons, Ltd.)

A general and reliable strategy for the detection of cocaine was proposed utilizing DNA-templated silver nanoclusters as signal indicators and the nicking endonuclease-assisted signal amplification method. This strategy can detect cocaine specifically with a detection limit as low as 2 nM by using a small volume of 5 μL.

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.

This paper deals with a novel approach to separate two analytes with different chemical properties and different lipophilicity. The newly described methodology is based on the two column system that was used for isocratic separation of two analytes with very different lipophilicity-dexamethasone and cinchocaine. Simultaneous separation of model compounds cinchocaine and dexamethasone was carried under the following conditions in two-column sequential injection chromatography system (2-C SIC). A 25×4.6 mm C-18 monolithic column was used in the first dimension for retention and separation of dexamethasone with mobile phase acetonitrile:water 30:70 (v/v), flow rate 0.9 mL min(-1) and consumption of 1.7 mL. A 10×4.6 mm C-18 monolithic column with 5×4.6 mm C-18 precolumn was used in the second dimension for retention and separation of cinchocaine using mobile phase acetonitrile:water 60:40 (v/v), flow rate 0.9 mL min(-1) and consumption 1.5 mL. Whole analysis time including both mobile phase's aspirations and both column separations was performed in less than 4 min. The method was fully validated and used for determination of cinchocaine and dexamethasone in pharmaceutical otic drops. The developed 2-C SIC method was compared with HPLC method under the isocratic conditions of separation on monolithic column (25×4.6 mm C-18). Spectrophotometric detection of both compounds was performed at wavelength 240 nm. System repeatability and method precision were found in the range (0.39-3.12%) for both compounds. Linearity of determination was evaluated in the range 50-500 μg mL(-1) and coefficients of determination were found to be r(2)=0.99912 for dexamethasone and r(2)=0.99969 for cinchocaine., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A simple and new method for the simultaneous determination of procaine (Pro), lidocaine (Lid), ropivacaine (Rop) and bupivacaine (Bup) was developed using capillary electrophoresis separation with mixed micelles and electrochemiluminescence detection. The use of mixed micelles of 2.0 × 10(-3)  mol/L sodium dodecyl sulfate (SDS) and 8.0 × 10(-3)  mol/L Tween 20 greatly improved separation selectivity. The detection sensitivities of four drugs with a Pt working electrode were increased by modification of the Pt electrode with europium(III)-doped Prussian Blue analog (Eu-PB). Under optimal conditions, the four local anesthetics were well separated and detected. The limits of detection (LOD, S/N = 3) of Pro, Lid, Rop and Bup in standard solution are 2.5 × 10(-8) , 1.3 × 10(-8) , 3.0 × 10(-8) and 4.1 × 10(-8)  mol/L, respectively. The limits of quantitation (LOQ, S/N = 10) of Pro, Lid, Rop and Bup are 2.3 × 10(-7) , 1.2 × 10(-7) , 3.7 × 10(-7) and 5.6 × 10(-7)  mol/L in a human urine sample, and 8.5 × 10(-7) , 6.9 × 10(-7) , 2.8 × 10(-6) and 1.1 × 10(-6)  mol/L in a human serum sample, respectively. The recoveries of four drugs at different spiked concentrations in human urine and serum samples were between 86.5 and 107.6%. The proposed method has been successfully applied to determine local anesthetics in biofluids., (Copyright © 2012 John Wiley & Sons, Ltd.)

The purpose of the present study is to determine the role of lidocaine, caffeine and dextromethorphan, used as adulterant substances, in five cases of drug overdose which have come to our attention. Taking into account the pharmacological mechanism, blood concentration and route of administration (intravenous) we evaluated the hypothesis that these substances could act with a synergistic effect - or at least additive - with the illicit drugs on the central nervous system and cardiovascular system., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)