title: Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.
abstract: A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring.
authors.affiliation: School of Life Science, Jilin University, Changchun, PR China.|Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, PR China.|Research Center for Drug Metabolism, Jilin University, Changchun, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: School of Life Science, Jilin University, Changchun, PR China.|Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, PR China.|Research Center for Drug Metabolism, Jilin University, Changchun, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Life and Medical Sciences, Dalian University of Technology, Panjin, PR China.
authors.forename: Meiyun
authors.initials: M
authors.lastname: Shi
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Life Science, Jilin University, Changchun, PR China.
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, Changchun, PR China.|Research Center for Drug Metabolism, Jilin University, Changchun, PR China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000927:Anticonvulsants / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D057230:Limit of Detection; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000927:Anticonvulsants
keywords: Antiepileptic drugs; Liquid chromatography; Tandem mass spectrometry; Therapeutic drug monitoring