Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls
ABSTRACT Referred to as 'spice', several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH-018 and a C(8) homologue of CP 47,497 were identified as major active ingredients. Due to their reported cannabis-like effects, many European countries have banned these substances. The World Anti-Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in-competition. Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase-I metabolism study of JWH-018 was presented yielding mainly hydroxylated and N-dealkylated metabolites. Due to these findings, a urine sample of a healthy man declaring to have smoked a 'spice' product was screened for potential phase-I and -II metabolites by high-resolution/high-accuracy mass spectrometry in the present report. The majority of the phase-I metabolites observed in earlier in vitro studies of JWH-018 were detected in this urine specimen and furthermore most of their respective monoglucuronides. As no intact JWH-018 was detectable, the monohydroxylated metabolite being the most abundant one was chosen as a target analyte for sports drug testing purposes; a detection method was subsequently developed and validated in accordance to conventional screening protocols based on enzymatic hydrolysis, liquid-liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis. The method was applied to approximately 7500 urine doping control samples yielding two JWH-018 findings and demonstrated its capability for a sensitive and selective identification of JWH-018 and its metabolites in human urine.
SourceAvailable from: Azamat Temerdashev[Show abstract] [Hide abstract]
ABSTRACT: History of the appearance and evolution of synthetic narcotics in recent years is presented. The main attention is paid to two classes of narcotic substances received the widest distribution in the world, i.e., cannabimetics and synthetic cations. The main classes,problems of identification, and approaches to the determination of new narcotics are considered. Approaches and solutions used in the quantitative analysis and screening of narcotics are discussed along with someaspects of sample preparation to their determination and matrix effects. The specific features of the determination of new narcotics in commercial products and biological samples are considered separately. Present�day methods of chromatography–mass spectrometry are most informative for timely revealing new narcotic substances, studying their metabolism, and developing reliable methods for the screening of native and biological samples.Journal of Analytical Chemistry 09/2014; DOI:10.1134/S1061934814090111 · 0.81 Impact Factor
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ABSTRACT: Synthetic cannabinoids, including JWH-018 and JWH-073, belong to a class of aminoalkylindoles (AAIs) that are smoked to produce an effect similar to tetrahydrocannabinol. Compounds in this class are often collectively known as 'Spice'. After ingestion, these compounds are extensively metabolized to their hydroxy and carboxylic acid metabolites. During forensic analysis, detection of these metabolites in urine is an indication of past exposure to the parent compounds. The analytical process involved hydrolysis of conjugated metabolites by glucuronidase, solvent extraction, derivatization by trifluoroacetic anhydride and hexafluoroisopropanol and GC-EIMS detection. Identification of the unknown was based on the criteria of GC retention time within ±2% and mass spectral ion ratio within ±20% of that of a standard. Deuterated internal standards of the carboxylic acid metabolites were used for quantification. The acid (JWH-018-COOH, JWH-073-COOH) and hydroxy (JWH-018-OH, JWH-073-OH) metabolites were linear over the concentration range of 0.1-10 and 0.2-10 ng/mL, respectively, with a correlation coefficient-square, R(2) > 0.999 (N = 5). Extraction recoveries of the metabolites were within 79 and 87%. The method was applied to 17 urine specimens collected as part of a military law enforcement investigation. Nine of the specimens tested positive for one or more of the metabolites. When the procedure was extended to screen other AAI compounds, two of the specimens were found to contain JWH-210, JWH-250 (JWH-302 or JWH-201) and JWH-250 (C4 isomers). The GC-EIMS method presented here was found to be suitable for detecting JWH-018 and JWH-073 metabolites and other AAI compounds in urine. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.Journal of analytical toxicology 02/2015; 39(3). DOI:10.1093/jat/bku178 · 2.63 Impact Factor
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ABSTRACT: In the last decade, an ever-increasing number of new psychoactive substances (NPSs) have appeared on the recreational drug market. To account for this development, analytical toxicologists have to continuously adapt their methods to encompass the latest NPSs. Urine is the preferred biological matrix for screening analysis in different areas of analytical toxicology. However, the development of urinalysis procedures for NPSs is complicated by the fact that generally little or no information on urinary excretion patterns of such drugs exists when they first appear on the market. Metabolism studies are therefore a prerequisite in the development of urinalysis methods for NPSs. In this article, the literature on the urinalysis of NPS metabolites will be reviewed, focusing on articles published after 2008.Bioanalysis 08/2014; 6(15):2083-107. DOI:10.4155/bio.14.168 · 3.03 Impact Factor