Simultaneous identification and quantification of synthetic cannabinoids (cannabimimetics) in serum, hair, and urine by rapid and sensitive HPLC tandem mass spectrometry screenings: overview and experience from routine testing

Abstract

Detection and quantification of synthetic cannabinoids (synonym: cannabimimetics) used as a substitute for natural cannabis has been a real toxicological and forensic issue since 2008. On the basis of a short overview of the pharmacological principle, chemical classification, and legal situation in Germany, the development of several analytical and screening approaches is presented. The paper further describes and validates a novel method for the simultaneous identification and quantification of JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, WIN48,098, WIN55,212-2, AM-694 and CP47,497 by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in human serum and hair using JWH-018-d 11 and THC-d 3 as internal standards. Detection limits ranging from 0.018 to 0.192 ng/mL for serum and from 0.140 to 0.820 pg/mg for hair, as well as very short retention times (up to 2.4 min), qualify this method, which presently includes 11 further compounds on a semi-quantitative basis, for rapid screening. The same method, using the deuterated 3-hydroxybutyl derivative of JWH-073, was applied for detection of 14 urinary metabolites after enzymatic hydrolysis of conjugates. Observation from routine analysis of 359 serum and 84 hair specimens reveals that concentrations of cannabimimetics in positive samples may differ by factors of at least 400 and 3000 with median values of 0.5 ng/mL and 9 pg/mg for serum and hair, respectively. Conclusions regarding consumption behaviors and strategies to decipher metabolic routes of these substances and possible implications are also discussed.

Multi‐class analysis of new psychoactive substances and metabolites in hair by pressurized liquid extraction coupled to HPLC‐HRMS

“…With respect to classical hair digestion with strong basic solutions (i.e., NaOH), PLE seemed more appropriate for multi‐class analysis considering that a number of compounds (e.g. cathinones), were not stable under the alkaline conditions used to completely dissolve the hair matrix . Moreover, significant matrix effects are usually reported with this kind of incubation since the hair matrix is completely dissolved and LLE, which is usually the technique for clean‐up, is not able to selectively extract the analytes.…”

“…There is still limited literature available about the analysis of NPS in hair samples and most methods involve gas chromatography coupled to mass spectrometry (GC‐MS) or (ultra)high performance liquid chromatography((U)HPLC)‐MS(/MS) as detection techniques and are limited to a single analyte or to groups of related substances (i.e., synthetic cannabinoids or cathinones together with phenetylamines or piperazines). Strano‐Rossi et al .…”

“…NPS extraction has been frequently performed by NaOH matrix dissolution followed by a suitable clean up step such as liquid‐liquid extraction (LLE) or solid‐phase extraction (SPE) . However, cathinones are unstable under these conditions . Alternative options consist of methanol or ethanol incubation for 3 to 16 h or overnight sonication with aqueous solutions (appropriate for cathinones and phenetylamines only) .…”

“…The detection of metabolites present in hair is, however, a desirable feature since it might facilitate differentiation between passive contamination and actual drug use. [8,9] There is still limited literature available about the analysis of NPS in hair samples and most methods involve gas chromatography coupled to mass spectrometry (GC-MS) [10][11][12][13] or (ultra)high performance liquid chromatography((U)HPLC)-MS(/MS) [7,8,[14][15][16][17][18][19][20][21][22][23][24] as detection techniques and are limited to a single analyte or to groups of related substances (i.e., synthetic cannabinoids or cathinones together with phenetylamines or piperazines). Strano-Rossi et al described the analysis of over 50 drugs, although their procedure was split into two separate extractions and included independent analytical methods for synthetic cannabinoids and cathinones.…”

Evolution of new narcotic substances and methods of their determination

“…In this case, the choice of a test sample and of target substances is determined by the challenges set before an analyst. Synthetic cannabimimetics and cathinones in the initial state can be found in hair [144][145][146][147][148][149], saliva [150][151][152][153][154][155][156][157], and blood preparations (serum or whole blood) [72,147,[158][159][160][161][162][163][164][165][166][167].…”