High-resolution mass spectrometric determination of the synthetic cannabinoids MAM-2201, AM-2201, AM-2232, and their metabolites in postmortem plasma and urine by LC/Q-TOFMS

Abstract

High-resolution mass spectrometry and accurate mass measurement by liquid chromatography/quadrupole-time of flight mass spectrometry (LC/Q-TOFMS) was applied to postmortem plasma and urine specimens from an autopsy of a fatal case involving synthetic cannabinoid use, resulting in the detection of three synthetic cannabinoids: MAM-2201, AM-1220, and AM-2232. We searched for their metabolites existing in postmortem plasma or urine by LC/Q-TOFMS and were able to detect N-dealkylated metabolites, defluorinated and further oxidized metabolites of MAM-2201, and some hydroxylated metabolites. Postmortem plasma concentrations of the parent drugs, N-dealkylated metabolites, and fluorinated and further oxidized metabolites of MAM-2201 were measured, and quantitation results revealed site differences between heart and femoral postmortem plasma concentrations of parent drugs and some metabolites, suggesting postmortem redistribution of the synthetic cannabinoids and their metabolites. Quantitation results suggest that defluorination is a major metabolic pathway for MAM-2201, and N-dealkylation is a common but minor pathway for the naphthoylindole-type synthetic cannabinoids in human.

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

“…plasma concentrations ranged from <0.1 to 49 ng/mL, indicating its extensive metabolism [19][20][21][25][26][27]. N-(5-hydroxypentyl)-MAM-2201, N-(4-hydroxyfluoropentyl)-MAM-2201, MAM-2201 pentanoic acid, and dealkyl-MAM-2201 have been identified as the metabolites of MAM-2201 in urine and hair samples from MAM-2201 abusers [27][28][29][30][31][32].…”

High-resolution mass spectrometry in toxicology: current status and future perspectives

“…QTOF HRMS quantification of the three synthetic cannabinoids MAM-2201, AM-1220, and AM-2232 in postmortem plasma and urine specimens was described by Zaitsu et al in the context of a case report (Zaitsu et al 2015). They also searched for plasma and urine metabolites and were able to detect N-dealkylated metabolites of AM-1220 and AM-2232 and defluorinated and further oxidized metabolites of MAM-2201.…”

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review

“…Furthermore, metabolism studies generally offer information on the CID pathways of NPS analogues since it is a conventional practice to determine the CID pathways of the parent molecule in order to identify the locations of metabolic transformations [48,[89][90][91][92][93][94][95][96][97]. As mentioned previously, the efficacy of bottom-up approaches largely relies on the acquisition of MS/MS and it has been suggested that DIA techniques should be used rather than DDA [86].…”

“…LC has been the most commonly adopted conventional separation technique coupled to HRMS for the analysis of NPS due to the well-recognized fact that analytes of interest do not need to be volatile and do not require derivatization [15,28,30,33,39,42,43,[46][47][48].…”