The objective of this study was to develop and validate a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of three tyrosine kinase inhibitors (ceritinib, osimertinib, and crizotinib) in human plasma using a single-step protein precipitation extraction. Chromatographic separation was achieved using a Waters X Bridge C18 (2.1 mm × 100 mm, 3.5 µm) and gradient elution with 0.2 % formic acid in water and acetonitrile. The total run time was 4.0 min, and the injection volume was 5 μL. The analytes were detected in the multiple reaction monitoring mode using electrospray ionization with positive ion mode. The m/z transitions of ceritinib, osimertinib, crizotinib and nilotinib were 558.0 → 433.2, 500.0 → 72.1, 450.0 → 259.3, and 530.0 → 289.1, respectively. The method was linear in the range of 2–500 ng/mL with lower limit of quantification of 2 ng/mL. Based on the guidelines on bioanalytical methods by the FDA, the validation studies demonstrated that the three analytes were both precise and accurate at four concentration levels, and the coefficient of variation was < 10.59 % and accuracy was > 88.26 %. We present a simple, rapid, and sensitive method for the simultaneous quantification of ceritinib, osimertinib, and crizotinib in human plasma by LC-MS/MS, which could be used in routine therapeutic drug monitoring.

本研究的目的是开发和验证一种简单、快速、灵敏的液相色谱-串联质谱 (LC-MS/MS) 方法，用于同时测定人体中的三种酪氨酸激酶抑制剂（色瑞替尼、奥希替尼和克唑替尼）血浆采用单步蛋白质沉淀提取。使用 Waters X Bridge C18 (2.1 mm × 100 mm, 3.5 µm) 和 0.2% 甲酸/水和乙腈梯度洗脱实现色谱分离。总运行时间为 4.0 分钟，进样量为 5 μL。使用正离子模式的电喷雾电离在多反应监测模式下检测分析物。m / z _色瑞替尼、奥希替尼、克唑替尼和尼罗替尼的转变分别为 558.0 → 433.2、500.0 → 72.1、450.0 → 259.3 和 530.0 → 289.1。该方法在 2–500 ng/mL 范围内呈线性，定量下限为 2 ng/mL。根据 FDA 的生物分析方法指南，验证研究表明，三种分析物在四个浓度水平上均准确无误，变异系数 < 10.59 %，准确度 > 88.26 %。我们提出了一种简单、快速、灵敏的方法，用于通过 LC-MS/MS 同时定量人血浆中的色瑞替尼、奥希替尼和克唑替尼，可用于常规治疗药物监测。