Chinese Journal of Chromatography ›› 2020, Vol. 38 ›› Issue (8): 900-905.DOI: 10.3724/SP.J.1123.2019.12025

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Simultaneous determination of twelve antiepileptic drugs in serum by ultra high performance liquid chromatography-tandem mass spectrometry

DAI Jing1, GAO Lehong2, PENG Fangda1, YU Lijia1, WANG Chaodong2, WANG Yuping2, DING Chunguang1,*()   

  1. 1 National Center for Occupational Safety and Health, Beijing 102308, China
    2 Xuanwu Hospital Capital Medical University, Beijing 100053, China
  • Received:2019-12-18 Online:2020-08-08 Published:2020-12-11
  • Contact: DING Chunguang
  • Supported by:
    Key Technology Project of State Administration of Work Safety(2017005);National Key Research and Development Program of China(2017YFC0907702)

Abstract:

A sensitive, high-throughput method was established for the simultaneous determination of 12 antiepileptics in serum by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The antiepileptics were gabapentin, lamotrigine, pregabalin, lacosamide, levetiracetam, topiramate, oxcarbazepine, clonazepam, sodium valproate, carbamazepine, phenobarbital and phenytoin sodium. Phenacetin and chlorzoxazone were used as internal standards. The antiepileptics and internal standards were extracted from serum by protein precipitation using acetonitrile as the precipitant. Chromatographic separation was achieved on an ACQUITY UPLC BEH C18 column with a gradient mobile phase comprising 10 mmol/L ammonium formate aqueous solution and methanol (containing 10 mmol/L ammonium formate) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode with ion mode switching. The results showed good linear trends in their respective concentration ranges and the correlation coefficients (r2) were greater than 0.992. The spiked recoveries of the 12 antiepileptics in serum were 90.80%-114.0% at the three spiked levels. The intra-assay (n=6) and inter-assay (n=3) precisions were less than 13.2% and 14.8%, respectively. The method has high specificity and sensitivity, and it can be used for clinical blood concentration monitoring and pharmacokinetic studies of the 12 antiepileptics.

Key words: ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), blood drug concentration, antiepileptics, serum