Elsevier

Legal Medicine

Volume 17, Issue 5, September 2015, Pages 421-426
Legal Medicine

Case Report
A fatal case of poisoning related to new cathinone designer drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and a dissociative agent, diphenidine

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Highlights

  • This is the first case report which describes a fatal poisoning case related to 3 cathinone derivatives, 4-methoxy PV8, PV9, and 4-methoxy PV9, and a dissociative agent, diphenidine.

  • Sensitive and reliable method to determine all these drugs together with 3 benzodiazepines and their metabolites in biological fluids was established by LC–MS/MS using the modified QuEChERS method.

Abstract

A woman in her thirties was found dead on a bed. Considerable amounts of “aroma liquid” and “bath salt” products and hypnotic drug tablets were scattered beside the bed. Autopsy showed pulmonary congestion and edema. Gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) analyses of “aroma liquid” and “bath salt” products showed the presence of new cathinone designer drugs, 4-methoxy PV8 (4-methoxy PHPP), PV9 (α-POP), and 4-methoxy PV9 (4-methoxy α-POP), and a dissociative agent, diphenidine. Drug screening in stomach contents, blood and hydrolyzed urine of the woman by GC–MS and liquid chromatography–tandem mass spectrometry (LC–MS/MS) revealed the presence of the above 4 types of drugs and 3 types of benzodiazepines, triazolam, flunitrazepam, and nitrazepam, and their metabolites. The above 7 drugs and 3 benzodiazepine metabolites were simultaneously determined by LC–MS/MS after modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) extraction using diazepam-d5 as the internal standard. The concentrations of 4-methoxy PV8, PV9, 4-methoxy PV9, and diphenidine in the femoral blood were 2.69, 0.743, 0.261, and 1.38 μg/ml, respectively, which were significantly higher than concentrations reported in previous cases. Alcohol concentration in the femoral blood was 1.52 mg/ml. Based on the pathological and toxicological findings, the cause of death was determined to be 3 types of cathinone drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and diphenidine poisoning under the influence of 3 benzodiazepines and alcohol.

Introduction

Abuse of synthetic cannabinoids, designer cathinones, and other new psychoactive substances has significantly increased in Japan over the last few years [1]. Harmful behaviors including violence, traffic accidents, self-injury, or suicide attempts under the influence of these drugs have become a serious social problem [2].

Here we report a fatal poisoning case in which new designer cathinones, 4-methoxy PV8 (4-methoxy PHPP), PV9 (α-POP), and 4-methoxy PV9 (4-methoxy α-POP), and a dissociative agent, diphenidine, were considered to be the causative drugs. Simultaneous determination of the above 4 drugs and 3 benzodiazepines and their metabolites was performed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) on whole blood, urine, and gastric contents of the decedent.

Section snippets

Case report

A woman in her thirties was found dead in the supine position on a bed. She had talked to her former boyfriend by phone 3 days prior, complaining that she had headache. Subsequently, he was unable to contact her. Considerable amounts of “aroma liquid” and “bath salt” products and hypnotic drug tablets were found scattered on the floor near the bed. An autopsy was performed approximately 4 days after the estimated time of death. On external examination, the cadaver was 164 cm tall and weighed 50 kg.

Reagents

4-Methoxy PV8, PV9, and 4-methoxy PV9 (Fig. 1) were purchased from Cayman Chemical (Ann Arbor, MI, USA). Diphenidine was purchased from Tocris Bioscience (Bristol, UK). Triazolam and α-hydroxytriazolam were provided by Pharmacia & Upjohn (MI, USA). Flunitrazepam and nitrazepam were provided by Eisai (Tokyo, Japan) and Sankyo (Tokyo, Japan), respectively. 7-Aminoflunitrazepam, 7-aminonitrazepam, and diazepam-d5 were purchased from Sigma–Aldrich (St. Louis, MO, USA). A QuEChERS pre-packed

Identification of 4-methoxy PV8, PV9, 4-methoxy PV9, and diphenidine in “aroma liquid” and/or “bath salt” products, and gastric contents of the victim by GC–MS

In the GC–MS analysis of the 5 “aroma liquid” products and 11 “bath salt” products that were found near the bed, 4 different compounds A–D were detected (Fig. 1), and the molecular weight of each compound was estimated to be 289, 273, 303, and 265, respectively based on the LC–MS analysis. Among 4 compounds, mass spectrum of compound B was matched to that of PV9 in the Cayman Spectral Library. However, the mass spectra of the other 3 compounds were not matched with any drugs in the library.

Conclusion

To our knowledge, this is the first report to describe a fatal case of poisoning related to 3 cathinone derivatives, 4-methoxy PV8, PV9, and 4-methoxy PV9, and diphenidine. All these drugs together with 3 benzodiazepines and their metabolites in biological fluids of the decedent were successfully determined by LC–MS/MS using the modified QuEChERS method. With the strengthening of the measures against the seller of these drugs, distributors continue the deal by switching to the use of delivery

Conflict of interest

The authors state no conflict of interest.

Acknowledgment

This study was supported in part by a Grant-in-aid for Scientific Research (C) (No. 26460881) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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