Drug Testing and Analysis最新文献

Drug checking services (DCS) are entities that allow recreational drug users to have street drug samples analyzed. Diverse analytical methods are applied for DCS, ranging from test strips to mass spectrometry (MS). This work evaluates the performance and utility of common methodologies used for DCS operating with off-site drug testing, while additionally assessing the potential of gas chromatography coupled to vapor phase infrared spectroscopy (GC-IR). Gas chromatography MS (GC-MS), GC-IR, and high-performance liquid chromatography with diode array detector (HPLC-DAD) were evaluated based on the analysis of 145 street drug samples obtained from two Swiss DCS. Additionally, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was applied and is briefly discussed. A combined total of 245 analytes (including adulterants and cutting agents) were detected. GC-MS presented the greatest number of detected compounds, with a sensitivity of 96% compared with the sum of all analytes, followed by HPLC-DAD with 82%, while GC-IR showed limited sensitivity with 70%. GC-IR underperformed regarding the detection of low-abundant adulterants and of the main active ingredients in strongly adulterated samples. This study discusses the limitations and strengths of the evaluated methods in the specific context of DCS, while providing insights into the occurrence of false declarations (differing analytical results compared with alleged drug identity) and the distributions of adulterants and cutting agents in street drug samples. Based on our results, complementary approaches are considered the most valuable. Finally, the promotion of comprehensive guidelines regarding the quality and suitability of analytical methods for DCS would be highly desired.

The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism and low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for detecting oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In this part of the work, the effect on the urinary steroid profile (SP) and the isotope ratio mass spectrometry (IRMS) markers were studied. Results showed that the 5α-androstane-3α,17β-diol/epitestosterone ratio is the most sensitive marker of the SP to detect oral T administration in Asian volunteers. All urines that led to suspicious urinary SP were concluded IRMS positive. However, for some subjects, the ABP Steroidal Module was unable to identify suspicious samples that were still detectable by IRMS. Positive IRMS samples were detected up to 24 h (n = 9), 36 h (n = 3), or 48 h (n = 1) after oral administration. Overall, the urinary SP together with IRMS allowed the detection of T administration in Asian volunteers. However, the detection windows are short, as reported for oral T administration in Caucasian volunteers. These findings highlight the need of implementing additional markers in the Steroidal Module of ABP that could enlarge detection windows.

The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism with low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for the detection of oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In the first part of the work, the effect on the urinary steroid profile (SP) and on the isotope ratio mass spectrometry markers was evaluated. In this second part, the effect on endogenous sulfate markers was evaluated. Results showed that the oral T administration is detected for a much longer period of time with sulfate markers than with the conventional urinary SP markers. Androstanediol sulfate 1 (Diol-S1)/dehydroandrosterone sulfate (DHA-S) and epiandrosterone sulfate (epiA-S)/DHA-S ratios were the most diagnostic parameters for longitudinal monitoring, as reported for Caucasian volunteers in a previous work. For most subjects, sulfate markers allowed the detection of suspicious samples up to 144 h. Combinations of sulfate and glucuronide markers improved the sensitivity in comparison with the conventional SP markers, but yielded poorer results than the best sulfate ratios. Based on the results of this study and previous works, sulfate EAAS metabolites provide a consistent improvement in the detectability of T administration in both Caucasian and Asian populations. Their incorporation into the ABP should be considered.

Methylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur-containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti-inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination of DMSO in horses has been reported; however, there has been no report on the elimination of MSM in horses. This paper describes a pilot study of an administration study of MSM in two geldings following one scoop (~15 g) of Pure MSM twice daily for six consecutive days. MSM in post-administration urine and blood samples was quantified by gas chromatography-mass spectrometry after sample dilution, with additional protein precipitation for the blood samples. The elimination profiles of MSM in urine and blood are described. The maximum detection time in urine at the IRL of 1200 μg/mL was around 4.5 days after the last dose. Plasma MSM in both horses was around 120 μg/mL at 4.4 days after the last dose, which was the last blood sample collected. As such, 120 μg/mL may indicate a possible IRL for controlling MSM in horse blood. The analysis of DMSO in post-MSM-administration samples showed that DMSO is not a significant metabolite of MSM in horses.

A new nicotine delivery system in the form of tobacco-free nicotine pouches was introduced in Europe in 2019. These nicotine bags did not fall under the Tobacco Products Directive (TPD) II, which brought forward regulatory requirements for both cigarettes, related products, and e-liquids. As these pouches did not fall under the scope of the TPD, it was up to the member states to decide which action to be taken if any. Some EU member states banned these nicotine pouches, while others put restrictions on the amount of nicotine, warning messages, and presentation and packaging of the product, and some member states did not take any action. Likely as a result of the ban or restrictions, soon after also, tobacco and nicotine-free pouches became available in the European Union (EU). Early 2024, "NoNIC" pouches, claiming to be tobacco- and nicotine-free, became available on the European market. These pouches are promoted online and clearly target a younger population with a youth-appealing package design and enticing flavors. Upon analysis of different samples utilizing gas chromatography coupled to MS (GC-MS), liquid chromatography coupled to high-resolution tandem mass spectrometry (HRAM LC-MS2), and nuclear magnetic resonance spectroscopy (NMR), it was demonstrated that these pouches were indeed devoid of nicotine but contained the synthetic nicotine homolog 6-methyl nicotine (6-MN) and this up to 20 mg per pouch. Nonetheless, a part of a likely unaware/misled young adult subpopulation has easy access to these products, containing a novel molecule for which limited to no clinical effects are known.

In 2009, levamisole was identified as a source for several aminorex positives reported in postrace equine samples in Canada. Since then, unexplained detections of aminorex continue to be identified in equine samples where there is no evidence to link these detections to a levamisole administration. Previous studies identified a compound named barbarin in some species of plants from the Brassicaceae family and suggested that barbarin may be a possible precursor for aminorex. The objectives of this study were to (1) investigate the link between barbarin and aminorex and (2) identify other biomarkers of plant origin. Methods were developed and validated for the detection of aminorex, barbarin, glucobarbarin, and other associated compounds. Aminorex was administered to one horse, and barbarin was not detected in any plasma and urine samples. Barbarea stricta and Barbarea orthoceras were administered to two horses, and aminorex was detected in all plasma and urine samples collected. Barbarin was detected in some plasma but not in urine samples. Resedine was observed in retrospective examination of chromatograms of the plant material and from all plants postadministration plasma and urine samples from the two horses. Resedine was administered to one horse and was detected in plasma and urine samples, but aminorex was only detected in urine samples. These results provide evidence that resedine is an intermediary compound between barbarin and aminorex in horses and that resedine can be used as a biomarker to eliminate the reporting of aminorex positives originating from the ingestion of plants from the Brassicaceae family.

This study presents the development and validation of a drug testing method in hair, employing a semi-automated sample preparation procedure and gas chromatography-tandem mass spectrometry (GC-MS/MS) for simultaneous multidrug analysis in hair. The method aims to detect and quantify multiple drugs in hair, including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, ketamine, norketamine, cocaine, benzoylecgonine, morphine, codeine and 6-monoacetylmorphine, using a comprehensive procedure involving decontamination, pulverization, clean-up using supported-liquid extraction (SLE) and a two-step derivatization process. The method validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, carryover, robustness and stability. The results indicate a linearity range of 0.1-5 ng/mg for all drugs except methamphetamine, which has a linearity range of 0.2-5 ng/mg. The accuracy and precision of the method are within ±20%, with the LOQ at 0.2 ng/mg for methamphetamine, 0.1 ng/mg for amphetamine and MDMA and 0.05 ng/mg for the rest of the drugs. The LODs were found to be 0.1 ng/mg for methamphetamine, 0.05 ng/mg for amphetamine and MDMA and 0.025 ng/mg for other drugs. This method has demonstrated its accuracy by comparing the quantitative test results with the expected results, using hair samples from the proficiency test service providers. This test method offers efficient testing of multiple drugs in a single analysis, significantly improves the hair analysis workflow in a routine testing laboratory by reducing turnaround time and the amount of hair sample required.

Wastewater (WW)-based epidemiology (WBE) is a powerful tool for screening and surveillance of drugs (of abuse) or new psychoactive substances (NPSs) in larger population. Since the drug market changes frequently, it is crucial for WBE to define screening and surveillance biomarkers considering drug metabolism and (microbial) stability. The aims of the presented work were first to identify metabolites, potentially serving as a WBE biomarker of five deschloroketamine derivatives (DCKDs) in rat feces samples after oral administration in addition to already known urinary metabolites, and second to elucidate the microbial biotransformation and WW stability of five DCKDs and their metabolites detected in urine and feces. Microbial biotransformation and stability of DCKD and their metabolites in WW were assessed by incubating parent compounds at 0.1 mg/L or rat urine or rat feces samples in freshly collected, untreated, influent WW over a period of 24 h. All samples were analyzed using liquid chromatography-high-resolution tandem mass spectrometry. All parent compounds, seven Phase I, and one Phase II metabolite were detected in rat feces samples. After WW incubations, all tested DCKD and their metabolites were still detectable at least in trace amounts, but particularly, peak areas of the Phase II N- and O-glucuronides showed a markable decrease. This is in line with previous findings where Phase II conjugates were identified to be unstable in WW and thus not recommended as a WW biomarker. Hence, incubations demonstrated that the five DCKD and most of their metabolites were sufficiently stable in WW influent and can thus be used as analytical targets in the context of WBE.

Synthetic opioids are a chemically diverse group of substances that function as central nervous system depressants, among which the 2-benzylbenzimidazole derivatives, also known as nitazenes or nitazene analogs, have recently emerged into the recreational market. The detection of these substances in biological samples largely relies on the acquisition of metabolic data. In this study, the first-phase metabolism patterns of methylenedioxynitazene, N-desethyl etonitazene, N-desethyl methylenedioxynitazene, ethyleneoxynitazene, N-pyrrolidino etonitazene, and N-desethyl isotonitazene utilizing human liver microsomes were investigated, and the metabolites were characterized through high-performance liquid chromatography-high-resolution tandem mass spectrometry. Two to eleven metabolites were identified for different nitazene analogs. It was observed that N-dealkylation, hydroxylation, and dehydrogenation were the major metabolic reactions, with other noteworthy metabolic reactions such as reduction, oxidation, and their combinations also identified. Therefore, it is recommended to use N-dealkylation and hydroxylation metabolites as analytical markers for monitoring of the intake of these substances.

Anabolic-androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their duration of action. As such, the detection of intact esters of endogenous steroids in hair is particularly advantageous, as it can provide unequivocal proof of their external origin. Compared with urine and blood matrices, hair in general allows a longer detection window as long as the administered drug can be incorporated into hair and has not degraded. This can be useful in doping control of equine sports, where the timing of sample collection may be critical due to the transient nature of AAS in other biological fluids. This paper describes the detection of AAS and/or their esters, as well as corticosteroids, in horse hair using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) after solid-supported liquid extraction (SLE) at basic pH. The developed UPLC-HRMS and GC-MS/MS methods in combination allowed the detection of 117 AAS, corticosteroids and/or their esters with estimated limits of detection down to sub-ppb levels and with good inter-day precision. Method applicability has been demonstrated through the detections of (i) boldenone undecylenate, nandrolone phenylpropionate and trenbolone acetate in three proficiency testing hair samples and (ii) nandrolone as a metabolite in a post-administration hair sample collected from a castrated horse having been administered nandrolone decanoate.