title: Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study.
abstract: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500μL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5μm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate.
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Dongminzhu Street, Changchun 130061, PR China; College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Tinglan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Heping
authors.initials: H
authors.lastname: Sun
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xiao
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China. Electronic address: yyan@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Dongminzhu Street, Changchun 130061, PR China; College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China; Research Center for Drug Metabolism, Jilin University, Qianjin Street, Changchun 130012, PR China. Electronic address: gujk@mail.jlu.edu.cn.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002260:Carboprost / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D005260:Female; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002260:Carboprost
keywords: Carboprost; Carboprost methylate; Dog; Esterase inhibitors; LC–MS/MS; Pharmacokinetics; Prodrug