Haloperidol, butyrophenone derivative, is a typical antipsychotic drug used in the treatment of schizophrenia, manic phase of bipolar disorder, and acute psychomotor agitations. According to the recent guidelines for therapeutic drug monitoring, it is strongly recommended to measure plasma level during the therapy with haloperidol. The objective of this study was to develop and validate a simple liquid chromatography–tandem mass spectrometry-based method to quantitate haloperidol in human plasma. After one-step extraction procedure using OSTRO^TM plate, gradient elution on Acquity UPLC BEH C18 (50 ×2.1mm, 1.7μm) column over 3.2 min was performed. The detection was conducted on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode in positive ionization mode with transitions at m/z 376.29 → 165.14 and m/z 380.28 → 169.17 for haloperidol and haloperidol-d₄ (used as an internal standard), respectively. The method was fully validated to cover wide concentration range of 0.05–80 ng/mL in human plasma and meets the criteria for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability. The extraction recovery was nearly 100%, and no significant matrix effects were observed. Therefore, the method is applicable to routine therapeutic drug monitoring in patients’ plasma.

中文翻译：

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开发用于定量人血浆中氟哌啶醇的高灵敏度和高通量液相色谱-串联质谱方法，并进行磷脂去除预处理

氟哌啶醇，丁酰苯衍生物，是一种典型的抗精神病药物，用于治疗精神分裂症、双相情感障碍的躁狂期和急性精神运动性躁动。根据最近的治疗药物监测指南，强烈建议在氟哌啶醇治疗期间测量血浆水平。本研究的目的是开发和验证一种基于液相色谱-串联质谱的简单方法，用于定量人血浆中的氟哌啶醇。使用 OSTRO ^TM板进行一步提取程序后，在 Acquity UPLC BEH C18 (50 ×2.1mm, 1.7μm) 柱上进行 3.2 分钟的梯度洗脱。检测是在三重四极杆串联质谱仪上通过多反应监测模式在正电离模式下进行的，跃迁在氟哌啶醇和氟哌啶醇-d ₄（用作内标）分别为m/z 376.29 → 165.14 和m/z 380.28 → 169.17 。该方法经过充分验证，涵盖了人血浆中 0.05–80 ng/mL 的宽浓度范围，符合选择性、线性和检测下限、精密度和准确度、基质效应、提取回收率、残留、稀释完整性和稳定。提取回收率接近 100%，未观察到显着的基质效应。因此，该方法适用于患者血浆中的常规治疗药物监测。