Citation

Yang L, Zhao J, Liu M, Li L, Yang H, Guo C, Hu J, Xiang P, Shen B, Qiao Z, Dang Y, Shi Y. Drug Test. Anal. 2021; 13(6): 1127-1135.

Copyright

(Copyright © 2021, John Wiley and Sons)

DOI

10.1002/dta.3012

PMID

33554459

Abstract

In recent years, diphenidol [1,1-diphenyl-4-piperidino-1-butanol] has been one of the drugs that appears in suicide cases, but there are few research data on its metabolic pathways and main metabolites. Metabolite identification plays a key role in drug safety assessment and clinical application. In this study, in vivo and in vitro samples were analyzed with ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry. Structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, 10 Phase I metabolites and 5 glucuronated Phase II metabolites were found in a blood sample and a urine sample from authentic cases. Three other Phase I metabolites were identified in the rat liver microsomes incubation solution. The results showed that the main metabolic pathways of diphenidol in the human body include hydroxylation, oxidation, dehydration, N-dealkylation, methylation, and conjugation with glucuronic acid. This study preliminarily clarified the metabolic pathways and main metabolites of diphenidol. For the development of new methods for the identification of diphenidol consumption, we recommend using M2-2 as a marker of diphenidol entering the body. The results of this study provide a theoretical basis for the pharmacokinetics and forensic scientific research of diphenidol.

Language: en

Keywords

Humans; Male; Animals; Rats; Chromatography, High Pressure Liquid; Rats, Sprague-Dawley; Mass Spectrometry; Antiemetics; Microsomes, Liver; metabolites; diphenidol; liquid chromatography-quadrupole/orbitrap mass spectrometry; liver microsomes; Piperidines; Species Specificity