Indexed by:期刊论文

Date of Publication:2016-03-01

Journal:JOURNAL OF SEPARATION SCIENCE

Included Journals:SCIE、EI、PubMed

Volume:39

Issue:5

Page Number:964-972

ISSN No.:1615-9306

Key Words:Antiepileptic drugs; Liquid chromatography; Tandem mass spectrometry; 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 mu L of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C-18 column (50 x 4.6 mm, 2.7 mu m) 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 mu g/mL for carbamazepine, 0.02 mu g/mL for lamotrigine, 0.01 mu g/mL for oxcarbazepine, 0.4 mu g/mL for 10-hydroxycarbazepine, 0.1 mu g/mL for carbamazepine-10,11-epoxide, 0.15 mu g/mL for levetiracetam, 0.06 mu g/mL for phenytoin, 0.3 mu g/mL for valproic acid, 0.03 mu g/mL for topiramate, and 0.15 mu g/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.