Pharmacokinetic profiles and egg residue patterns of levamisole in laying hens at two dosing rates and two routes of administration.

The levamisole maximum residue limit for edible fat, kidney, and muscle of chickens is 0.01 mg/kg. However, no maximum residue limit has been established for eggs. In the present study, the pharmacokinetic profile and levamisole residue in the eggs from laying hens were investigated using ultra-performance liquid chromatography-tandem mass spectrometry. A single dose of levamisole (30 mg/kg) was administered via the intramuscular or oral route, and an additional egg residue study was performed with 300 or 600 mg/kg commercial LEV drug (30 or 60 mg/kg as levamisole) orally. The limit of quantification was 0.0056 µg/mL and 0.0015 mg/kg for plasma and eggs, respectively. The plasma concentration was below the limit of quantification 10 and 12 h after intramuscular and oral administration, respectively. The half-life of the absorption phase was comparable between the intramuscular and oral routes, which was approximately 1 h, and the mean maximum concentration value was significantly higher in intramuscular (2.29 ± 0.30 µg/mL) than in oral (1.45 ± 0.38 µg/mL) route. The relative oral bioavailability after intramuscular administration was 92.3%. In the egg residue study, dose-dependent area under concentration and maximum concentration were observed after single oral administration of 30 and 60 mg/kg egg residue, and the calculated withdrawal period for both 30 and 60 mg/kg groups based on the positive list system standard (0.01 mg/kg) was 7 d after the treatment.

Analysis of tetramisole metabolites - Is "Aminorex" found in forensic samples of cocaine users actually 4-phenyl-2-imidazolidinone?

Phenyltetrahydroimidazothiazole (PTHIT, tetramisole) is a common adulterant in cocaine samples. Little is known about its human metabolism. p-hydroxy-PTHIT has long been the only proven phase-I-metabolite. Another putative metabolite is the stimulant aminorex. However, data on its analytical proof is rare and contradictory. Even less known is its constitutional isomer 4-phenyl-2-imidazolidinone which has only been proven in animal samples so far. The aim of the study was to get insight into the metabolism of PTHIT after controlled nasal uptake of PTHIT and in real forensic cocaine/benzoylecgonine-positive samples. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated for quantification of 4-phenyl-2-imidazolidinone and p-hydroxy-PTHIT (LOQ 0.05 ng/ml each). Selectivity was ensured for 4-phenyl-2-imidazolidinone and aminorex (LOD 0.05 ng/ml). After controlled nasal uptake of tetramisole (10 mg, n = 3) a shorter half-life for p-hydroxy-PTHIT (3.4-5.8 h) was determined than for 4-phenyl-2-imidazolidinone (14.0-15.9 h). p-hydroxy-PTHIT (33%) and 4-phenyl-2-imidazolidinone (51%) were also detected in serum samples from cocaine users tested previously positive for PTHIT (n = 73). Aminorex was never detected. The potential of misinterpreting 4-phenyl-2-imidazolidinone as aminorex was tested using a gas chromatography-mass spectrometry (GC-MS) method used in the literature and an in-house liquid chromatography-time-of-flight mass spectrometry (LC-QTOF) screening-method. Using GC-MS the analysed bis-trimethylsilyl-derivatives cannot be differentiated due to co-elution. Both substances were chromatographically separated using the LC-QTOF method, but library comparison workflows misinterpreted 4-phenyl-2-imidazolidinone as aminorex. It seems likely that aminorex, which was allegedly identified as a metabolite of PTHIT in samples of cocaine users in previous studies, is in fact 4-phenyl-2-imidazolidinone.

Quantitative Analysis of Abamectin, Albendazole, Levamisole HCl and Closantel in Q-DRENCH Oral Suspension Using a Stability-Indicating HPLC-DAD Method.

Combination therapy of many anthelmintic drugs has been used to achieve fast animal curing. Q-DRENCH is an oral suspension, containing four different active drugs against GIT worms in sheep, commonly used in Australia and New Zeeland. The anti-parasitic drugs are Albendazole (ALB), Levamisole HCl (LEV), Abamectin (ABA), and Closantel (CLO). The main purpose of this study is to present a new simultaneous stability-indicting HPLC-DAD method for the analysis of the four drugs. The recommended liquid system was 1 mL of Triethylamine/L water, adjusting the pH to 3.5 by glacial acetic acid: acetonitrile solvent (20:80, v/v). Isocratic elusion achieved the desired results of separation at a 2 mL/min flow rate using Zorbax C-18 as a stationary phase. Detection was performed at 210 nm. The linearity ranges were 15.15 to 93.75 µg/mL for ALB, 25 to 150 µg/mL for LEV, 30 to 150 µg/mL for ABA, and 11.7 to 140.63 µg/mL for CLO. Moreover, the final greenness score was 0.62 using the AGREE tool, which reflects the eco-friendly nature. Moreover, the four drugs were determined successfully in the presence of their stressful degradation products. This work presents the first chromatographic method for simultaneous analysis for Q-DRENCH oral suspension drugs in the presence of their stressful degradation products.

Chiral pharmacokinetics of tetramisole stereoisomers-Enantioselective quantification of levamisole and dexamisole in serum samples from users of adulterated cocaine.

Phenyltetrahydroimidazothiazole (PTHIT, tetramisole) is the most frequently used adulterant of cocaine and exists in the two enantiomeric forms levamsiole (S) and dexamisole (R). Existing studies show diverse fractions of samples containing enantiopure levamsiole, levamisole-enriched mixtures, and racemic tetramisole as adulterant. However, blood samples have never been enantioselectively tested for PTHIT. Because enantiomers are usually metabolized stereoselectively, chiral analysis of blood samples can help estimate the time of drug use, provided that a racemic substance is ingested. Therefore, an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed using a chiral column. Validation of the method was carried out for methanolic substance samples as well as serum samples and showed satisfactory selectivity, sensitivity, linearity (0.05-100 ng/mL), precision, and accuracy; 151 cocaine samples seized in Germany between 2018 and 2021 were analyzed. Most (94%, n = 48) of the 51 PTHIT-positive samples contained racemic tetramsiole, whereas there were two samples containing levamisole-enriched mixtures and one sample containing nearly enantiopure levamisole. Furthermore, 157 cocaine and/or benzoylecgonine-positive forensic serum samples were tested with cocaine-positive samples showing the highest frequency of PTHIT detection (43%). All positive samples contained either dexamisole alone or (R)/(S)-concentration ratios >1 (1.05-70.6). Finally, a self-administration study was conducted with three subjects taking 10 mg of racemic tetramisole each. Although peak concentrations and corresponding times did not differ significantly between the enantiomers, dexamisole showed significantly longer apparent elimination half-lives (7.02-10.0 h) than levamisole (2.87-4.77 h). The resulting steadily increasing (R)/(S)-ratios can therefore be helpful in estimating the time of cocaine consumption.

Cutting agents in cocaine: A temporal study of the period 2015-2017 in the Northern Region of Colombia.

Cocaine is a naturally occurring psychostimulant drug available worldwide. Drug trafficking networks adulterate pure cocaine with cutting agents to increase their earnings. This study presents a descriptive statistical analysis of the cutting agents found in 2118 cocaine samples that were seized in the Northern Region of Colombia (in the period 2015-2017). The data used in this study was drawn from the GC-MS analytical reports of the National Institute of Legal Medicine and Forensic Sciences -Colombia, Northern Region. Results showed diverse cutting agents in seized cocaine samples, from which the most commonly used are caffeine, phenacetin, lidocaine, imidazole and levamisole. In addition, cocaine samples showed different mixtures of the above cutting agents, predominantly caffeine/phenacetin and caffeine/lidocaine/phenacetin mixtures.

Development and Validation of a Highly Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique to Determine Levamisole in Plasma and Saliva.

BACKGROUND: Levamisole is used as a steroid-sparing drug for the treatment of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome in children. As part of a large multicentre randomized controlled trial with levamisole, pharmacokinetic and pharmacodynamic parameters of levamisole in children with idiopathic nephrotic syndrome were investigated, as well as the feasibility of using saliva as an alternative and patient-friendly matrix for determining levamisole concentrations. In this study, the authors presented the development and validation of a highly sensitive method for determining levamisole in plasma and saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: In 100 µL samples, proteins were precipitated with 750 µL acetonitrile/methanol 420:80 (v/v) with levamisole-D5 as an internal standard. Calibration standards were prepared over a range of 0.1 ng/mL-50 ng/mL. To determine ultrafiltration efficiency, the ultrafiltrate was obtained by centrifuging blank plasma samples over the filter. Both filtered and nonfiltered samples were analyzed. RESULTS: For plasma, accuracy and within-run and between-run imprecision were between 95.0% and 100% and <14.5%, respectively, and for saliva, between 100.9% and 107.5%, and <13.3%. No significant matrix effects were observed. Samples were stable at benchtop for 24 hours and -80°C, for at least 14 months (stability experiments ongoing). The ultrafiltration efficiency of unbound concentrations in plasma was lower than 85% (58.9%) but stable, and, therefore, the observed concentration should be corrected. CONCLUSIONS: Based on observations, the developed measure can determine levamisole concentrations in participant saliva samples.

A fatal case after an intravenous injection of levamisole.

Levamisole is a drug originally prescribed as an antihelmintic. Because of the occurrence of severe cases of agranulocytosis and leukoencephalitis it was removed from the French market in 1998 for human use, while it remains available for veterinary use. Nowadays in France its only use in humans is regulated by authorization for temporary use for its immunomodulatory properties in the treatment of nephritic syndrome.A 52-year-old man was found dead at his farm. Injection points were observed on his arm and a syringe containing a dark orange-brown liquid was found near the body. At his home, the discovery of a letter highlighted suicidal intent. Analysis of the aforementioned liquid, peripheral blood and urine confirmed the unique presence of levamisole. The femoral blood concentration of levamisole was of 25 mg/L whereas the femoral blood concentrations reported in cases of fatalities after cocaine use do not exceed 0.0056 mg/L. In humans, levamisole can be detected in biological samples after cocaine use as this drug is also an adulterant and one of its metabolites (aminorex) seems to have amphetamine-like properties. In this case, the man consumed levamisole from time to time for its stimulant and strengthening effects.Cases of fatal poisoning using levamisole are very rare and poorly documented, which makes the interpretation of postmortem blood levamisole concentration difficult.

Cocaine Consumption and Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis: A Case Report.

ABSTRACT: Cocaine is often sold in a mixture with levamisole to increase the profit margin and potentiate the euphoric effect. Apart from an overdose, cocaine can induce a wide range of clinical symptoms. We present a case of cocaine/levamisole-induced pauci-immune glomerulonephritis. A 22-year-old patient was sent to the hospital after a laboratory result showed an unexpected acute kidney injury, with an estimated glomerular filtration rate of 34 mL/min/1.73 m2. The medical history included cocaine abuse. Renal biopsy showed a pauci-immune necrotizing glomerulonephritis. Antineutrophil cytoplasmic antibodies were positive with a perinuclear staining pattern and target specificity for leucocyte myeloperoxidase (antimyeloperoxidase). Despite treatment, the kidney function did not show significant improvement. The forensic implication of this case is that even if the toxicological values are not high enough to suggest a lethal intoxication, an idiosyncratic reaction on cocaine and/or levamisole has to be taken into account.

Drug checking services at music festivals and events in a Canadian setting.

OBJECTIVES: Drug checking is a harm reduction intervention that allows for identification of drug composition. The objective of the study was to assess drug market components and concordance between expected substance reported by clients and results from point-of-care drug checking at music festivals and events in British Columbia. METHODS: From July to September 2018, we provided drug checking services at four events using combination Fourier Transform Infrared (FTIR) spectroscopy and fentanyl immunoassay strips. We measured concordance between expected substance as reported by clients to the results from the FTIR/fentanyl immunoassay strip and tracked unexpected adulterants. RESULTS: In total, 336 checks were completed. Most samples were expected by clients to be psychedelics (69.3%) or stimulants (19.6%). Of the 233 psychedelic samples, 169 (72.5%) contained the expected, unadulterated substance, and 27 (11.6%) contained additional contaminants. Of 66 stimulant samples, 41 (62.1%) contained expected substance, while 24 (36.4%) contained additional contaminants. Unexpected adulterants such as fentanyl, levamisole, and phenacetin were also found, in addition to several novel psychoactive substances. DISCUSSION: We found a large proportion of substances that contained unexpected adulterants. Our findings highlight the value of continued drug checking and will be helpful in designing future harm reduction interventions in similar contexts.

Adulterants in crack cocaine in Brazil.

INTRODUCTION: Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. METHOD: We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. RESULTS: Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). CONCLUSION: Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Adulterants in crack cocaine in Brazil / Adulterantes no crack vendido na "Cracolândia"

Abstract Introduction Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. Method We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. Results Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). Conclusion Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Resumo Introdução O Brasil é o maior consumidor mundial de crack, e a dependência é um grande problema de saúde pública. Este é o primeiro estudo a investigar a prevalência de adulterantes potencialmente nocivos presentes em amostras de cabelo de pacientes brasileiros com dependência de crack. Métodos Foram avaliados adulterantes em amostras de cabelos extraídos por conveniência de 100 pacientes internados na unidade de observação de 48 horas do Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), o maior centro de tratamento de dependência do Brasil. Uma análise transversal foi realizada com os dados obtidos. Resultados Foram encontrados adulterantes em 97% das amostras de cabelo analisadas. O adulterante mais prevalente foi a lidocaína (92%), seguida da fenacetina (69%) e levamisol (31%). Conclusão Os adulterantes foram amplamente prevalentes em amostras de cabelo de usuários de crack tratados no CRATOD: pelo menos um adulterante estava presente em praticamente todas as amostras de cabelo coletadas. Isso aponta para a necessidade de monitorar os efeitos adversos no ambiente clínico, a fim de proporcionar a esse grupo de pacientes de alto risco cuidados imediatos e efetivos relacionados às complicações agudas e crônicas associadas a esses adulterantes.

Distribution and elimination of levamisole in eggs and tissues after oral administration to laying hens, determined by LC-MS/MS.

Levamisole was administered to laying hens, and concentrations in eggs and tissues (thigh muscle, breast muscle, liver and kidney) were determined by a newly developed liquid chromatography tandem mass spectrometry method, which allowed trace level quantification of levamisole. The adopted analytical method showed good sensitivity, repeatability and percentage of recovery from spiked matrices. Maximum concentrations of levamisole were found on the first day after the administration (531.1 µg/kg in liver, 164.3 µg/kg in egg yolk, 130.7 µg/kg in kidney, 78.0 µg/kg in breast muscle, 70.7 µg/kg in thigh muscle and 64.0 µg/kg in egg white), after which there is a decline. The compound was rapidly eliminated from eggs, with a half-life of 1.3 days. Elimination appeared to be slower in thigh muscle (3.5 days), breast muscle (3.4 days) and liver (3.3 days). According to this experiment, the levamisole withdrawal periods calculated for eggs, liver, kidney, breast muscle and thigh muscle in laying hens were 14.1, 6.1, >4.0, 14.5 and 13.0 days, respectively. The longest time for levamisole residues to be completely released from tissues was seen in liver samples (37.4 days), followed by thigh muscle, breast muscle and kidney. Elimination from eggs was fastest (16.4 days for levamisole residues to drop below the method quantification limit).

Profiling cocaine residues and pyrolytic products in wastewater by mixed-mode liquid chromatography-tandem mass spectrometry.

This work provides a new analytical method for the determination of cocaine, its metabolites benzoylecgonine and cocaethylene, the pyrolytic products anhydroecgonine and anhydroecgonine methyl ester, and the pharmaceutical levamisole in wastewater. Samples were solid-phase extracted and extracts analyzed by liquid chromatography-tandem mass spectrometry using, for the first time in the illicit drug field, a stationary phase that combines reversed-phase and weak cation-exchange functionalities. The overall method performance was satisfactory, with limits of detection below 1 ng/L, relative standard deviations below 21%, and percentages of recovery between 93% and 121%. Analysis of 24-hour composite raw wastewater samples collected in Santiago de Compostela (Spain) and Brasilia (Brazil) highlighted benzoylecgonine as the compound showing the highest population-normalized mass loads (300-1000 mg/day/1000 inhabitants). In Brasilia, cocaine and levamisole loads underwent an upsurge on Sunday, indicating a high consumption, and likely a direct disposal, of cocaine powder on this day. Conversely, the pyrolytic product resulting from the smoke of crack, anhydroecgonine methyl ester, and its metabolite anhydroecgonine were relatively stable over the four days, agreeing with a non-recreational-associated use of crack.

Role of TiO2 Nanoparticles and UV Irradiation in the Enhancement of SERS Spectra To Improve Levamisole and Cocaine Detection on Au Substrates.

The original goal of this study was the employment of surface-enhanced Raman spectroscopy (SERS) for the analysis of real cocaine samples (containing adulterants) on composite Au-TiO2 nanomaterials to achieve low detection limits suitable for the analysis of illicit drugs and controlled substances and to exploit the photodegradation activity of TiO2 to recycle the SERS substrate for repeated analyses. The photodegradation (self-cleaning) effects of the Au-TiO2 composite nanomaterials by ultraviolet (UV) radiation are known. These effects were investigated on large-area SERS substrates immersed in the TiO2 nanoparticle aqueous suspension. The cocaine samples were measured on electrochemically gold-plated platinum targets. Surprisingly, the intensity of SERS spectra of the pure cocaine did not change after immersion in a suspension of TiO2 under UV irradiation. However, for some real cocaine samples, the overall intensity of the SERS spectra was even higher after the treatment by TiO2 and UV radiation as compared to the usual Au substrate. This unexpected signal amplification (valuable for illicit drug detection) was found to be caused mainly by the contained levamisole, which is used as a medical drug and is one of the frequent adulterants of cocaine. Both the sole effect of TiO2 on the levamisole spectrum intensity and the role of UV irradiation were inspected separately. Finally, an investigation of both the TiO2 and UV radiation treatments was performed, demonstrating (i) the necessity of both factors for selective SERS signal enhancement of the adulterant and (ii) the revision of general anticipation of the role of TiO2 in SERS systems.

Detection of Cutting Agents in Drug-Positive Seized Exhibits within the United States.

The following report summarizes a study performed on seized drug exhibits collected in two U.S. states to evaluate the presence and identification of cutting agents. Aliquots of seized drug materials from Kentucky (n = 200) and Vermont (n = 315) were prepared using a dilute-and-shoot procedure. Initial analysis was performed using gas chromatography-mass spectrometry (GC-MS) followed by analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF). Active compounds detected overall included caffeine (31.0%), quinine/quinidine (24.7%), levamisole (11.6%), acetaminophen, (8.2%) and procaine (8.2%). These compounds were found with several drugs of abuse, such as heroin, fentanyl, methamphetamine, and cocaine. This novel information about cutting agents used to dilute or alter drugs of abuse is important to criminal investigations and in the management of acute intoxications at health centers. However, common methodologies for analysis and standard reporting practices frequently do not include cutting agents, resulting in lacking or inadequate information regarding prevalence of these substances.

Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long-term monitoring of its intake by chiral LC-MS/MS analysis of cocaine-positive hair samples.

Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R-/S-phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine-positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine-positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). For distinction of levamisole/dexamisole chiral LC-MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut-off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT-adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non-racemic PTHIT. Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.

Report: An ex vivo up-take of levamisole molecules by cestode (Monezia expensa) of goat (Capra hirsa) and its detection through RP-HPLC.

Detection of various molecules of drugs remained a prime issue especially in tissues of animals, humans and in their target parasites. The cestode/tapeworms pose a dilemma because of their weird body composition and uptake pattern of nutrients and medicines especially through absorption by tegument. We selected levamisole; thought to be potent antiparasitic/ani-cestodal drug. The uptake of levamisole (LEV) through cestodeal tissues is studied through HPCL in this paper. High performance liquid chromatography technique has been utilized to know the uptake of levamisole in tissues of cestodes of Goat (Monezia expensa) in small ruminants. The drug was exposed to M. expensa by in vitro till its death or a parasite ceases its movement. The tissue/ part of proglattids of the M. expensa were homogenized with some modifications and levamisole extraction was performed with liquid phase extraction method. The evaporation of solvent was done and the residual cestodal tissues were cleaned by solid phase. After the solid phase extraction method, the recovery of drug, detection and quantification of levamisole from cestodal tissues was determined through Reverse Phase Column High Performance Liquid Chromatography (RP-HPLC). Levamisole (LEV) molecules assay was obtained on a C18 reverse-phase (20um, 6mm x 150mm) column at flow rate of 1ml/min using acetonitrile and ammonium acetate as mobile phase and UV detection was done at 254nm. The development of method of Levamisole (LEV) detection from cestodal tissues by HPLC in vitro samples has been demonstrated first time in Pakistan, which can provide the solution of parasitic control and provide in sight in to the uptake of anti cestodal drugs either against human or livestock parasites.

Polymer platforms for selective detection of cocaine in street samples adulterated with levamisole.

Accurate drug detection is of utmost importance for fighting against drug abuse. With a high number of cutting agents and adulterants being added to cut or mask drugs in street powders the number of false results is increasing. We demonstrate for the first time the usefulness of employing polymers readily synthesized by electrodeposition to selectively detect cocaine in the presence of the commonly used adulterant levamisole. The polymers were selected by computational modelling to exhibit high binding affinity towards cocaine and deposited directly on the surface of graphene-modified electrodes via electropolymerization. The resulting platforms allowed a distinct electrochemical signal for cocaine, which is otherwise suppressed by levamisole. Square wave voltammetry was used to quantify cocaine alone and in the presence of levamisole. The usefulness of the platforms was demonstrated in the screening of real street samples.

Practical tool for sampling and fast analysis of large cocaine seizures.

Large quantities of illicit drugs are frequently seized by law enforcement. In such cases, a representative number of samples needs to be quickly examined prior to destruction. No procedure has yet been set up which rapidly provides information regarding the homogeneity of the samples, the presence of controlled substances, and the degree of purity. This study establishes a protocol for fast analysis of cocaine and its most common cutting agent, levamisole, in large seizures. The protocol is based on a hypergeometric sampling approach combined with Fourier-transform infrared (FTIR) spectrometry and support vector machines (SVM) algorithms as analysis methods. To demonstrate the practical use of this approach, 5 large cocaine seizures (consisting between 45 and 85 units) were analysed simultaneously with gas chromatography-mass spectrometry (GC-MS), gas chromatography-flame ionisation detector (GC-FID), and a portable FTIR spectrometer using attenuated total reflectance (ATR) sampling combined with SVM models. According to the hypergeometric sampling plan of the guidelines of the Drugs Working Group (DWG) of the European Network of Forensic Science Institutes (ENFSI), the required number of subsamples ranged between 19 and 23. Considering the identification analyses, the SVM models detected cocaine and levamisole in all subsamples of Cases 1 to 5 (100% correct classification), which was confirmed by GC-MS analysis. Considering the quantification analyses, the SVM models were able to estimate the cocaine and levamisole content in each subsample, compared to GC-FID data. The developed strategy is easy, cost effective, and provides immediate information about both the presence and concentration of cocaine and levamisole. By using this new strategy, the number of confirmation analyses with laborious and expensive chromatographic techniques could be significantly reduced.

Analysis of cocaine adulterants in human brain in cases of drug-related death.

For different reasons, street cocaine is often diluted with pharmacologically active substances, the so-called adulterants such as levamisole or hydroxyzine. A controversial debate exists currently on the uptake of adulterants from cocaine preparations and drug-related death. Previous research convincingly argues that serious adverse side effects that affect the central nervous and cardiovascular systems can be a consequence of adulterated cocaine. AIMS: Having identified the presence of adulterants in lung tissue and blood, the concentrations of these substances in brain, an important target location, was of interest. This provides an opportunity to assess their role in cases of drug-related deaths. MATERIALS AND METHODS: We developed and validated a method for the analysis of cocaine, two cocaine metabolites and six adulterants, which can typically be found in cocaine preparations, and one adulterant metabolite in brain tissue by gas chromatography-mass spectrometry (GC-MS)1. Ten brain samples which were tested positive for cocaine were analyzed. The homogenized brain tissue was embedded into drying paper for protein precipitation. During a subsequent solid-phase extraction (SPE), the eluate and one of the wash fractions were collected. After derivatization with N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in pyridine and isooctane, the extracts were analyzed by GC-MS. RESULTS AND DISCUSSION: The method was fully validated for cocaine (COC), benzoylecgonine (BZE), ecgonine methyl ester (EME), diltiazem (DIL), hydroxyzine (HYD), and levamisole (LEV) and partly validated for cetirizine (CET), lidocaine (LID), phenacetin (PHE), and procaine (PRO) in brain material. By analyzing post-mortem brain tissue of ten cocaine users, LEV, LID, and HYD as well as PHE were identified in contrast to DIL, PRO, and the HYD metabolite CET. HYD and LEV were found in moderate to high concentrations in some cases. Therefore, it cannot be excluded that they have caused adverse side effects. CONCLUSION: Because adulterants can potentially affect the central nervous and cardiac systems, it is likely that they enhance COC toxicity.