Drug Design, Development and Therapy (2021-02-01)

Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Simultaneous Determination of Antipsychotic Drugs in Human Plasma and Its Application in Therapeutic Drug Monitoring

  • Qi Y,
  • Liu G

Journal volume & issue
Vol. Volume 15
pp. 463 – 479

Abstract

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Yingjie Qi, Guangxuan Liu Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, Liaoning Province, People’s Republic of ChinaCorrespondence: Yingjie QiDepartment of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Number 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People’s Republic of ChinaTel +8618909811762Email [email protected]: We developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous therapeutic drug monitoring (TDM) and clinical pharmacokinetic antipsychotic drugs: clozapine (CLP), chlorpromazine (CPZ), risperidone (RPD), paliperidone (PLD), quetiapine (QTP;), aripiprazole (APZ), dehydroaripiprazole (DAP), olanzapine (OZP), ziprasidone (ZRD), and amisulpride (ASP).Methods: Analytes and internal standards (ISs) were separated using a Phenomenex phenyl-hexyl column (50.0 × 2.1 mm, 1.7 μm) with water containing 0.1% formic acid and 2 mM ammonium acetate, and methanol containing 0.1% formic acid and 2 mM ammonium acetate as the mobile phase. The antipsychotic drugs and ISs were extracted from 50 μL of plasma using acetonitrile.Results: The calibration ranges were 25.0– 1500.0 ng/mL for CLP, CPZ, DAP, and QTP, 10.0– 600.0 ng/mL for CPZ and ZRD, 2.5– 150.0 ng/mL for RPD, 5.0– 300.0 ng/mL for PLD and OZP, and 20.0– 1200.0 ng/mL for ASP. Validation was carried out according to the guidelines for bioanalytical validation, including assessment of calibration curves, specificity, accuracy, precision, recovery, stability, dilution integrity, and matrix effect. All the results satisfied the requirements.Conclusion: The results provided significant information to support future clinical TDM and rational drug use research. The proposed method also provided a simple, reliable, specific, and suitable technique for TDM and pharmacokinetic studies.Keywords: UPLC, tandem mass spectrometry, antipsychotic drug, therapeutic drug monitoring, individualized therapy

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