GC-MS analysis of underivatised new psychoactive substances in whole blood and urine

Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. In 2009 and 2010, a significant rise in the abuse of a new group of synthetic cathinones was reported in Western Europe. In 2010, the rapid emergence of a new drug of abuse, referred to as bath salts or "legal high," occurred in the USA. The growing number of cases along with the alarming severity of the effects caused by the abuse of these substances prompted significant concern from both healthcare providers and legal authorities. We report the experience of the first 8 months of two regional poison centers after the emergence of a new group of substances of abuse. This was a retrospective case series of patients reported to two poison centers with exposures to bath salts. Additionally, 15 "product samples" were obtained and analyzed for drug content using GC/MS. There were 236 patients of which 184 (78%) were male. Age range was 16-64 years (mean 29 years, SD 9.4). All cases were intentional abuse. There were 37 separate "brand" names identified. Clinical effects were primarily neurological and cardiovascular and included: agitation (n = 194), combative behavior (n = 134), tachycardia (n = 132), hallucinations (n = 94), paranoia (n = 86), confusion (n = 83), chest pain (n = 40), myoclonus (n = 45), hypertension (n = 41), mydriasis (n = 31), CPK elevations (n = 22), hypokalemia (n = 10), and blurred vision (n = 7). Severe medical outcomes included death (n = 1), major (n = 8), and moderate (n = 130). Therapies included benzodiazepines (n = 125), antipsychotics (n = 47), and propofol (n = 10). Primary dispositions of patients were: 116 (49%) treated and released from ED, 50 (21%) admitted to critical care, 29 (12%) admitted to psych, and 28 (12%) lost to follow up. Nineteen patients had blood and/or urine analyzed using GC/MS. MDPV was detected in 13 of 17 live patients (range 24-241 ng/mL, mean 58 ng/mL). The four samples with no drug detected, reported last use of bath salts >20 h prior to presentation. Three of five patients had MDPV detected in urine (range 34-1386 ng/mL, mean 856 ng/mL). No mephedrone or methylone was detected in any sample. Quantitative analysis performed on postmortem samples detected MDPV in blood at 170 ng/mL and in urine at 1400 ng/mL. No other synthetic cathinones were detected. This is the first report of MDPV exposures with quantitative blood level confirmation. Clinical effects displayed a sympathomimetic syndrome, including psychotic episodes often requiring sedation, movement disorders, and tachycardia. Within 8 months of their appearance, 16 states had added synthetic cathinones to the controlled substances list as a Schedule I drug. We report the emergence of a new group of substances of abuse in the USA, known as bath salts, with quantitative results in 18 patients. State and federal authorities used timely information from poison centers on the bath salt outbreak during investigations to help track the extent of use and the effects occurring from these new drugs. Close collaboration between state authorities and poison centers enhanced a rapid response, including legislation.

In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

This publication reports analytical properties of a new hallucinogenic substance identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine]. The identification was based on results of comprehensive study including several analytical methods, i.e., GC-EI-MS (without derivatization and after derivatization with TFAA), LC-ESI-QTOF-MS, FTIR and NMR. The GC-MS spectrum of 25C-NBOMe was similar to those obtained for other representatives of the 25-NBOMe series, with dominant ions observed at m/z=150, 121 and 91. Fragment ions analogic to those in 2C-C (4-chloro-2,5-dimethoxy-β-phenylethanamine) were also observed, but their intensities were low. Derivatization allowed the determination of molecular mass of the investigated substance. The exact molecular mass and chemical formula were confirmed by LC-QTOF-MS experiments and fragmentation pattern under electrospray ionization was determined. The MS/MS experiments confirmed that the investigated substance was N-(2-methoxy)benzyl derivative of 2C-C. The substance was also characterized by FTIR spectroscopy to corroborate its identity. Final elucidation of the structure was performed by NMR spectroscopy.