Method Validation of Seven Synthetic Cathinones by LC–MS-MS Analysis and the Prevalence of N-Ethylpentylone in Postmortem Casework

Author(s):  
Alexander D Giachetti ◽  
Joseph H Kahl ◽  
M Elizabeth Zaney ◽  
George W Hime ◽  
Diane M Boland

Abstract N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016 to 2018. There is limited information regarding the toxicity of NEP; however, the few published reports suggest that NEP can cause serious toxic effects and sudden death. The purpose of this publication is to describe a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method for seven synthetic cathinones (methylone, ethylone, butylone, dibutylone, alpha-Pyrrolidinopentiophenone (α-PVP), pentylone and NEP) and to present a detailed summary regarding the presence of NEP in postmortem casework at the Miami-Dade Medical Examiner Department. Postmortem iliac blood, serum, liver and brain specimens were prepared by solid-phase extraction with analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. Analyte linearity was established from 0.01 to 0.5 mg/L on a six-point calibration curve. A total of 101 NEP quantitations were performed using this method. Concentrations in postmortem case samples ranged from 0.01 to 2.7 mg/L. Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n = 72) across all causes and manners of death. Approximately half of the cases were homicides in which the decedent was the victim of gunshot wounds or stabbing. Two of the three highest concentration cases of NEP (2.7 and 1.7 mg/L) involved 38-year-old white males who were tasered by police prior to death. The psychostimulant effect of NEP may result in an excited delirium and/or hallucinogenic state. The concentration of NEP detected in accidental intoxication and polydrug cases overlapped with those attributed to other causes, including homicides and police-involved deaths.

2021 ◽  
Author(s):  
Chen-Yu Gao ◽  
Jian-Qiang Xi ◽  
Ding-Zhong Song ◽  
Jie Yuan ◽  
Wu-Si Hao ◽  
...  

AbstractPeripheral CB1R blockers without crossing the blood–brain barrier (BBB) have demonstrated therapeutic benefits in metabolic syndromes, including obesity. Among them is Alisol G, a tetracyclic triterpene from Alismatis rhizoma (zexie), which can effectively reduce the weight of obese mice. Results from CP55940-induced [35S] GTPγS cannabinoid-type 1 receptor (CB1R) binding assay show an IC50 of 34.8 μmol/L for Alisol G, implicating its role as a CB1R antagonist. The purpose of our study is to assess whether Alisol G could serve as a peripheral CB1R antagonist for obesity treatment. In this study, we build a simple, reliable, and sensitive method to detect the concentration of Alisol G in rat tissue by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that Alisol G was mainly distributed in intestinal midgut, mucosa and small intestine, with little brain exposure. We suggested that intestine may be the main acting sites of Alisol G. Through comparison of brain and blood concentrations of Alisol G, our data showed that Alisol G cannot penetrate the BBB easily. In conclusion, Alisol G may represent a peripheral CB1R antagonist for the further treatment of obesity.


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