The continual emergence of new psychoactive substances remains a global health issue. We reported a case of serotoninergic syndrome following the consumption of 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 25H-NBOH documented by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS).

A 23-year-old man, with a history of cathinone regular use, presented a seizure and a loss of consciousness 30min after the consumption of a powder identified as 25I-NBOH. The way of exposure was not documented. On arrival at the mobile emergency unit, the patient exhibited a serotonin syndrome with hyperthermia at 41°C, hypertonia of the upper limbs, bilateral mydriasis, Glasgow coma 3, hypertension at 16/8, tachycardia at 180 bpm, and SaO₂=50%. During the hospitalization, he developped acute renal failure, acute liver failure, rhabdomyolysis and disseminated intravascular coagulation. He was discharged after 20 days of hospitalization but kept neurological sequelae. Following his hospital admission, blood and urine samples were drawn and sent to the toxicology laboratory to determine the cause of poisoning.

In total, 200μL of plasma and urine samples were extracted with QuEChERS salts and acetonitrile. The extracts were analyzed by liquid chromatography hyphenated to high-resolution mass spectrometry (Orbitrap, Exploris 120) allowing both a non-targeted screening and the simultaneous quantification of 132 compounds frequently found in poisonings. Analysis was realized in full scan experiment with a nominal resolving power of 60,000 FWHM within the 125–650m/z mass range, followed by four cycles of DDA with a mass resolution of 16,000 FWHM.

Pharmaceuticals administered to the patient during his medical care were found in plasma and urine: midazolam, hydroxyzine and its metabolite cetirizine, ketamine, etomidate, laudanosine (atracurium metabolite), lidocaine. Additionally, two NPS were identified and then confirmed with certified reference materials (CRM): MDPHP in plasma and urine, and 25H-NBOH in urine. 25H-NBOH was not detected in plasma despite a limit of detection being 0.01ng/mL. Unfortunately, there were not enough remaining samples after the screening analyzes, therefore the quantification could not be carried out. In order to estimate the concentration, a calibration curve was carried out with the two compounds under the same conditions as the screening analysis (same pretreatment, same internal standards at the same concentrations, as well as the same analytical conditions), and the data corresponding to the initial acquisition was then reprocessed. MDPHP concentration was 1ng/mL in plasma and 48ng/mL in urine, 25H-NBOH concentration was 0.4ng/mL in urine. 25I-NBOH was specifically searched in both samples and was not detected.

MDPHP is a synthetic cathinone of the pyrovalerone type (e.g. MDPV), it acts as a stimulant on the release of dopamine and norephedrine and simultaneously as reuptake inhibitor, causing a pronounced stimulatory effect on the central nervous system (Grapp M, et al., Drug Test Anal 2020;12:1320–35). 25H-NBOH is a psychedelic belonging to the NBOMe family, they are potent agonists of 5-HT2A receptor (Pottie et al., Biochem Pharmacol 2020;182:114251). The clinical manifestations observed here are similar to those described in cases of NBOMe poisoning, and are probably attributable to 25H-NBOH, they may have been potentiated by the presence of MDPHP (Kyriakou C, et al., Eur Rev Med Pharmacol Sci 2015;19:3270–81). To our knowledge, very few study have been dedicated to MDPHP poisoning, and this is the first describing 25H-NBOH poisoning.