title: A chiral high-performance liquid chromatography-tandem mass spectrometry method for the stereospecific determination of morinidazole in human plasma.
abstract: Morinidazole is a novel 5-nitroimidazole derivative used for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections. Morinidazole possesses a chiral carbon and is clinically administered as a racemate. In the present study, an enantioselective and sensitive liquid chromatography-tandem mass spectrometry method of determining morinidazole enantiomers in human plasma was developed and validated to characterize the stereoselective pharmacokinetics. Plasma samples were processed by liquid-liquid extraction using tert-butyl methyl ether. Chiral separation was optimized within 8.5min on a cellulose column using an isocratic mobile phase of methanol/water (80:20, v/v). Detection was using mass spectrometry in multiple reaction monitoring mode, using the transitions of m/z 271→144 for morinidazole enantiomers, and m/z 275→148 for d4-morinidazole (internal standard). The calibration curves were linear over 5.00-6000ng/mL for each enantiomer. The lower limit of quantification for each enantiomer was established at 5.00ng/mL. Intra- and inter-day precisions were less than 6.4% for each enantiomer in terms of relative standard deviation, and accuracies were between -2.5% and 6.4% in terms of relative error for each enantiomer. No chiral inversion was observed during sample storage, preparation procedure and analysis. Major glucuronide and sulfate conjugates were not observed to interfere with the determination of morinidazole enantiomers. The method was applied to study the stereoselective pharmacokinetics of morinidazole in humans. Moderate stereoselectivity was observed in healthy subjects and patients with severe renal impairment.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhong
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Jiangsu Hansoh Pharmaceutical Co., Ltd., 9 Dongjin Road, Lianyungang 222069, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China. Electronic address: xychen@mail.shcnc.ac.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D059625:Liquid-Liquid Extraction; D008738:Methyl Ethers; D009593:Nitroimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D008738:Methyl Ethers; D009593:Nitroimidazoles; C043243:methyl tert-butyl ether; C547405:morinidazole
keywords: 5-Nitroimidazole antimicrobial drug; Liquid chromatography–tandem mass spectrometry; Morinidazole enantiomer; Stereoselective pharmacokinetics