Toxicological detection of the new psychoactive substances MDPHP and MDPHpP in human urine samples by elucidation of their urinary metabolites using gas chromatography–mass spectrometry

The continuous emergence of new psychoactive substances on the illicit drug market provides challenges for forensic and clinical analytics. Reliable detection of previous ingestion of these drugs in human urine samples requires elucidation of target metabolites and, in the case of gas chromatography-mass spectrometry (GC-MS), the knowledge of their derivatized mass spectra. The study presented here focused on the two pyrrolidinophenones 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 3,4-methylenedioxy-α-pyrrolidinoheptanophenone (MDPHpP), which could be identified in 25 and 3 authentic cases, respectively. Using a standard analytical procedure by means of full-scan GC-MS after acid hydrolysis and acetylation, phase I metabolites of both substances were identified in authentic urine samples by elucidation of their mass spectral fragmentation patterns. The postulated phase I metabolic steps of MDPHP and MDPHpP comprised demethylenation followed by methylation of the methylenedioxy moiety, oxidation of the pyrrolidine ring, N,N-bisdealkylation of the pyrrolidine ring to its primary amine, and hydroxylation of the aliphatic side chain. Various combinations were detected. Acetylated mass spectra of the metabolites were provided for both substances. The analogy in mass fragmentation of the proposed metabolites for the homologous parent compounds indicated a high plausibility. Based on the frequency of occurrence and abundances of the metabolites in the urine samples, target analytes for both substances and base peak fragment ions for specific mass search could be recommended for the mentioned procedure: m/z 140, 154, and 86 for MDPHP and m/z 154, 168, and 100 for MDPHpP. The study could support the detection of these new substances in forensic and clinical cases.