Case report of a drug-related death following the use of cathinone derivatives (MPHP and 4-MEAP)

Abstract

The consumption of new psychoactive substances (NPS), such as cathinones, has been on the rise over the last few years, with adverse effects ranging from agitation, anxiety and hallucinations to convulsions, severe cardiac, hepatic and renal failures [1] . This work aims to report and discuss a fatal case related to the concomitant use of two cathinone derivatives (CDs). A 39-year-old man, known for drug addiction history, was found dead in his caravan. Multiple injection points were observed. The medical examiners concluded to a non-specific asphyxia syndrome combined with pulmonary and pericerebral edema and multivisceral congestion. Hence, the hypothesis of a death related to drug abuse was retained. Blood and urine samples were collected for NPS identification and quantification using LC-HRMS. A metabolic study using human liver microsomes was also conducted to identify human metabolites compared to published studies in animals. Ethanol concentrations were determined using GC-FID and toxicological screenings were performed using LC-UVDAD, LC-MS/MS and GC-MS. Various analyses detected the presence of two CDs, 4′methyl-α-pyrrolidinohexanophenone (MPHP) and N-ethyl-4′methylnorpentedrone (4-MEAP), as well as tetrahydrocannabinol [(THC): 1.4 μg/L and (THC-COOH): 6.6 μg/L] and ethanol (0.5 g/L in cardiac blood). The concentrations of MPHP/4-MEAP in the femoral blood, cardiac blood and urine were 47/1.6, 97/3.5 and 2380/49,700 μg/L, respectively. The in vitro metabolic study allowed us to identify five metabolites for MPHP and three for 4-MEAP, but only two metabolites were detected at low levels in biological samples. One metabolite of MPHP, the 4′-carboxy-PHP, was detected in all biological samples, with higher chromatographic signals than those of MPHP. Regarding the growing phenomenon of CD abuse, analytical toxicologists must have: – efficient tools to detect such NPS focusing on relevant biomarkers; – interpretation data (toxic and fatal blood levels) on CD. In this study, the CD concentrations found appeared to be of the same order of magnitude as the only two reports found in the literature, one concerning a case of death due to MPHP with a plasma (supernatant of heart blood) concentration of 32.9 μg/L [2] and another one on two cases of 4-MEAP intoxication with a positive outcome showing urine concentrations of 7676 and 4554 μg/L, respectively [3] . It is very likely that an additive or synergistic effect between both CDs might have precipitated the fatal outcome.