title: Elucidation of in vitro phase I metabolites of droperidol using UPLC-QTOF MS.
abstract: Droperidol, an antidopaminergic drug clinically used as an antiemetic and antipsychotic, has been reported to induce cardiac toxicity in patients. Due to the close relationship between drug metabolism and efficiency and toxicity, the present study aims to investigate the phase I metabolites using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The NADPH-supplemented phase I incubation system was used to elucidate the in vitro phase I metabolites. Five metabolites were detected after droperidol was incubated with phase I incubation mixture, including one hydrogenated droperidol, three oxidative metabolites, and one N-dealkylated droperidol, elucidated by individual retention time and MS/MS fragmentation. Due to the existed phase II metabolic reaction, further phase II metabolism should be investigated in the future. In conclusion, the phase I metabolism of droperidol was investigated in the present study, and five new metabolites were identified. The efficiency and toxicity of these phase I metabolites should be investigated in the future.
authors.affiliation: Pharmacy Department, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515031, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.forename: Chao-Xian
authors.initials: CX
authors.lastname: Lin
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Lin-Shu
authors.initials: LS
authors.lastname: Zhao
authors.forename: Shu-Yao
authors.initials: SY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D003640:Dealkylation; D065127:Dopamine D2 Receptor Antagonists / Q000737:chemistry / Q000378:metabolism*; D004329:Droperidol / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006865:Hydrogenation; D008297:Male; D050216:Metabolic Detoxication, Phase I; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D015394:Molecular Structure; D010084:Oxidation-Reduction; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D004329:Droperidol