title: Simultaneous determination of benzimidazoles and their metabolites in plasma using high-performance liquid chromatography/tandem mass spectrometry: application to pharmacokinetic studies in rabbits.
abstract: An HPLC/MS/MS method was developed for the simultaneous determination of the following benzimidazole anthelmintics and metabolites in plasma: flubendazole, albendazole, fenbendazole, mebendazole, thiabendazole, hydrolyzed flubendazole, albendazole sulfoxide, albendazole sulfone, albendazole aminosulfone, oxfendazole, fenbendazole sulfone, aminomebendazole, hydroxymebendazole, and 5-hydroxythiabendazole. The sample preparation process involved a pH-dependent extraction of the analytes. Chromatographic separation was performed on a C18 column with a mobile phase gradient starting with methanol-water (20 + 80, v/v) containing 0.1% formic acid. The overall average recoveries of the analytes based on a matrix-matched calibration ranged from 75.0 to 120.0%, with RSD values of <20.0%. The LODs ranged from 0.08 to 2.0 microg/kg and the LOQs from 0.3 to 5.0 microg/kg. The validated method was used in pharmacokinetic studies of benzimidazole compounds in rabbits, and the elimination of the metabolites was measured quantitatively.
authors.affiliation: China Institute of Veterinary Drug Control, Beijing 100081, People's Republic of China. zhuxinle@ivdc.gov.cn
authors.forename: Xinle
authors.initials: X
authors.lastname: Zhu
authors.forename: Shuhuai
authors.initials: S
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Congmin
authors.initials: C
authors.lastname: Zhang
authors.forename: Shixin
authors.initials: S
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010865:Pilot Projects; D011817:Rabbits; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles