Testing for designer stimulants: Metabolic profiles of 16 synthetic cathinones excreted free in human urine

Abstract

The study of 34,561 urine specimens, submitted for designer stimulant testing between February 2011 and January 2013, provided an opportunity: to estimate the range of synthetic cathinones (SC) abused in the USA, to observe multiple examples of metabolic profiles for each drug in various stages of excretion in human urine, to evaluate the extent of metabolism of specific SC and to select metabolites or parent drugs for routine testing. Sixteen SC were found in random patient samples: buphedrone; butylone; 3,4-dimethylmethcathinone; ethcathinone; N-ethylbuphedrone; ethylone; flephedrone; mephedrone; 4-methylbuphedrone; 3,4-methylenedioxypyrovalerone (MDPV); 4-methyl-N-ethylcathinone; methylone; pentedrone; pentylone; α-pyrrolidinobutiophenone (PBP) and α-pyrrolidinopentiophenone (PVP). After liquid/liquid extraction and trifluoroacetylation, specimens were screened by gas chromatography-mass spectrometry (GC-MS) for drugs and metabolites excreted free in urine. Each SC exhibited a characteristic metabolic profile, as shown by multiple examples. Metabolites' structures were postulated on the basis of their mass spectra. A large group of SC appears to metabolize extensively by carbonyl reduction into respective substituted ephedrines and further by N-dealkylation into norephedrines. Abundant metabolites in this group are essential markers of the parent drug use. Unchanged drugs are far less abundant or not found at all. SC with methylenedioxy attachment to the aromatic ring, metabolize by carbonyl reduction to a much lesser extent and are best detected as such in free urine fraction. PBP and PVP can be detected either unchanged or as metabolites, resulting from pyrrolidine ring degradation into primary amine followed by carbonyl reduction. MDPV appears in urine as such with no apparent free metabolites.