Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
J Pharm Biomed Anal. 2021 Jan 30;193:113733. doi: 10.1016/j.jpba.2020.113733. Epub 2020 Nov 2.
Multiple small-molecule kinase inhibitors with specific molecular targets have recently been developed for the treatment of cancer. This article reports the development and validation of an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method to simultaneously analyse the small-molecule kinase inhibitors dacomitinib, ceritinib, lorlatinib, and nintedanib in human plasma. For chromatographic analyte separation, an Acquity UPLC® BEH C18 column 1.7 μm, 50 mm x 2.1 mm was used with a binary gradient of pure water/formic acid/ammonium formate (100:0.1:0.02, v/v/v) and methanol/formic acid (100:0.1, v/v). Calibration curves for all small-molecule kinase inhibitors were 5.00-500 ng/mL. Validation of this method met all requirements of the Food and Drug administration. Additionally, clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung cancer.
多种具有特定分子靶点的小分子激酶抑制剂最近已被开发用于癌症治疗。本文报告了一种超高效液相色谱/串联质谱（UPLC-MS/MS）方法的开发和验证，该方法可同时分析人血浆中的小分子激酶抑制剂达可替尼、塞瑞替尼、劳拉替尼和尼达尼布。对于色谱分析物的分离，使用 Acquity UPLC® BEH C18 柱（1.7μm，50mm×2.1mm），采用纯水/甲酸/甲酸铵（100:0.1:0.02，v/v/v）和甲醇/甲酸（100:0.1，v/v）的二元梯度洗脱。所有小分子激酶抑制剂的校准曲线范围为 5.00-500ng/mL。该方法的验证符合食品和药物管理局的所有要求。此外，通过对肺癌患者药代动力学研究中的多个样本进行定量，证明了该方法的临床适用性。
