Fatal intoxication involving 3,4-methylenedioxy-derived designer drugs

Background and Aim Belonging to the class of synthetic cathinones, 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) is a 3,4-methylenedioxy-derived designer (MDD) drug with a pyrrolidine moiety and an alkyl portion with six carbon atoms. Other MDD pyrrolidine derivatives belong to the alkyl homologous series (C3-C5) and are the 3,4-methylenedioxy-pyrovalerone (MDPV), 3,4-Methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP) and 3,4-3’,4’-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP). MDPHP was notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) for the first time in 2014 and in Italy is a controlled substance since 2014, firstly as analogue of cathinone and then as a single compound in 2020. Only two cases of death involving MDPHP have been published so far. In the case reported here, a 69‐year‐old Caucasian man with a history of chemsex practices was found dead in a waterway. During the autopsy, no evidence of natural disease or trauma was found to account for the death. Blood (both peripheral and central), urine, bile, vitreous humor, gastric content, brain, liver, kidney, lungs, and pubic hair specimens were collected and submitted for toxicological analysis. Methods MDPHP and MDPV were detected and quantified by both GC-MS and UHPLC-MS/MS analysis using methods purposely developed. MDPPP and MDPBP were identified in the same specimens by HPLC-HRMS (not quantified yet). Results The peripheral blood and urine concentrations were 354 and 1940 ng/mL for 3,4-MDPHP and 0,1 for 0,8 ng/mL for MDPV, respectively. No other drugs of abuse nor ethanol were found in blood and urine specimens. Citalopram and 7-aminoclonazepam were also detected at the concentration of 528 and 353 ng/mL in peripheral blood, 4134 and 137 ng/mL in urine, respectively. MDD metabolites were further investigated by HPLC-HRMS. The combined circumstantial elements and toxicological results of the case revealed the occurrence of an acute multidrug intoxication produced by MDPHP and clonazepam in presence of MDPPP, MDPBP, MDPV and citalopram. Conclusion To the best of our knowledge, this is the first fatal intoxication case reported involving multiple 3,4-methylenedioxy-derived designer drugs and with MDPHP and MDPV post-mortem concentrations in body tissues, fluids and body hair. This study underlined that the adoption of validated analytical methods for the detection of a large number of NPS with an appropriate sensitivity is pivotal for forensic toxicology laboratories.