Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring

Mai Shibata, Sachiyo Hashi, Haruka Nakanishi, Satohiro Masuda, Toshiya Katsura, Ikuko Yano

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50μL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C18 column with a gradient mobile phase of 10mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r2<0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics.

Original languageEnglish
Pages (from-to)1519-1528
Number of pages10
JournalBiomedical Chromatography
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 1 2012
Externally publishedYes

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Drug Monitoring
Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Anticonvulsants
Mass spectrometry
zonisamide
formic acid
etiracetam
felbamate
Monitoring
Carbamazepine
Phenytoin
Phenobarbital
Pharmaceutical Preparations
Methanol
Assays
Nordazepam
Nitrazepam
Ethosuximide

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring. / Shibata, Mai; Hashi, Sachiyo; Nakanishi, Haruka; Masuda, Satohiro; Katsura, Toshiya; Yano, Ikuko.

In: Biomedical Chromatography, Vol. 26, No. 12, 01.12.2012, p. 1519-1528.

Research output: Contribution to journalArticle

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