title: Enantioselective HPLC determination and pharmacokinetic study of secnidazole enantiomers in rats.
abstract: Secnidazole is a long-lasting nitroimidazole antimicrobial agent that is used as racemic mixture in clinical settings. We developed and validated an enantioselective high-performance liquid chromatography method to determine secnidazole enantiomers in rat plasma. Secnidazole enantiomers and S-(-)-ornidazole (internal standard) were extracted from 50 μL of rat plasma using diethyl ether-dichloromethane (3:2, v/v). Baseline resolution (Rs=2.45) was achieved within 7.0 min on a Chiral-AGP column (150 mm × 4.0mm, 5 μm) at 20°C. The mobile phase consisted of 10mM ammonium acetate-methanol (96:4, v/v) and was delivered at a flow rate of 0.5 mL/min with ultraviolet detection at 318 nm. The method was linear over the concentration range 0.500-100 μg/mL for both enantiomers. The lower limit of quantification was 0.500 μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.8-8.6 and 1.8-8.2% for S-(+)-secnidazole and R-(-)-secnidazole, respectively. The relative error values of accuracy ranged from -7.8 to 1.1% for S-(+)-secnidazole and from -7.3 to -0.1% for R-(-)-secnidazole. The method was successfully used to determine the pharmacokinetic properties of secnidazole enantiomers in rats after administration of the racemate and individual enantiomers. The pharmacokinetic results indicate that the disposition of secnidazole enantiomers is not stereoselective and chiral inversion and enantiomer-enantiomer interaction do not occur in rats.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors: Jiangbo
authors: J
authors: Du
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors: Yifan
authors: Y
authors: Zhang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors: Yao
authors: Y
authors: Chen
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors: Dongqin
authors: D
authors: Liu
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors: Xiaoyan
authors: X
authors: Chen
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China. Electronic address: dfzhong@mail.shcnc.ac.cn.
authors: Dafang
authors: D
authors: Zhong
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D008795:Metronidazole; C016724:secnidazole
keywords: Enantiomers; Enantioselective high-performance liquid chromatography; Pharmacokinetics; Secnidazole