Development of a simultaneous analytical method for clozapine and its metabolites in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry with linear range adjusted by in-source collision-induced dissociation

Toshihiro Sato, Masato Suzuka, Yuji Sato, Riko Iwabuchi, Daisuke Kobayashi, Jiro Ogura, Shinya Takasaki, Maki Yokota, Taku Tsukamoto, Yoshihiro Hayakawa, Masafumi Kikuchi, Masamitsu Maekawa, Nariyasu Mano

研究成果: Article査読

抄録

Clozapine (CLZ) is a key drug in treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of CLZ and its metabolites, N-desmethylclozapine and clozapine N-oxide, is required to monitor and manage the risks of side effects. Although quantification methods for TDM have been developed for CLZ and its metabolites, they were not sufficiently accurate for the quantification of CLZ owing to the upper limits of the calibration curves. An analytical method using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry was developed and validated for the simultaneous measurement of CLZ and its metabolites in human plasma. To expand the concentration range of the calibration curves, we used a linear range shift technique using in-source collision-induced dissociation (CID). Using our approach, the linearity and quantitative range were improved compared to those reported by previous studies, and were sufficient for TDM in clinical practice. The intra- and inter-assay accuracy was 84.6%–114.8%, and the intra- and inter-assay precisions were ≤9.1% and ≤9.9%, respectively. Moreover, all samples from patients with treatment-resistant schizophrenia were successfully quantified. Therefore, our novel analytical method using in-source CID had the appropriate performance to measure the plasma concentrations of CLZ and its metabolites for TDM in clinical practice.

本文言語English
論文番号e5094
ジャーナルBiomedical Chromatography
35
7
DOI
出版ステータスPublished - 2021 7

ASJC Scopus subject areas

  • 分析化学
  • 生化学
  • 分子生物学
  • 薬理学
  • 創薬
  • 臨床生化学

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