Ultrafast and high-throughput quantitative analysis of carbamazepine in human plasma by direct analysis in real time tandem mass spectrometry coupled with solid phase extraction to eliminate matrix effects

Abstract

Therapeutic drug monitoring of carbamazepine is necessary for its clinical application with the purpose to reach therapeutic concentration and reduce the risk of concentration-dependent toxicity. An ultrafast analytical assay for quantification of carbamazepine in human plasma was developed and validated based on direct analysis in real time tandem mass spectrometry (DART-MS/MS). After reversed phase solid phase extraction with Waters Oasis HLB, carbamazepine and internal standard carbamazepine-D₂N¹⁵ were monitored by positive ion mode followed by multiple reaction monitoring (MRM) of the transitions at m/z 237.1→194.0 and 240.1→196.2, respectively. The DART-MS/MS method is ultrafast and high-throughput and the analytical time for each sample is only 0.4 min. The assay was linear in the concentration range 0.50-30 μg/mL and intra- and inter-day accuracies were within ± 15% and trueness were < 13.9% at all concentrations. The method was successfully applied to therapeutic drug monitoring of carbamazepine in human plasma.

Keywords: Carbamazepine; DART-MS/MS; Therapeutic drug monitoring.