Journal of Chromatography B ( IF 2.8 ) Pub Date : 2021-01-18 , DOI: 10.1016/j.jchromb.2021.122554 Johannes J.M. Rood , Javier Sastre Toraño , Victor J. Somovilla , Jos H. Beijnen , Rolf W. Sparidans
Erlotinib is a first-generation epithelial growth factor receptor inhibitor used in the treatment of non-small cellular lung cancers. Our previously published method on a Thermo TSQ Quantum Ultra triple quadrupole mass spectrometer for the quantitation of erlotinib, OSI-420, and OSI-413 and some other kinase inhibitors was transferred to a more sensitive Sciex QTRAP5500 system. Both methods showed comparable performance in the previous range (5–5000 and 1–1000 ng/mL for erlotinib and OSI-420) with comparable accuracies and precisions (98.9–106.2 vs 98.7.0–104.0, and 3.7–13.4 vs 4.6–13.2), and a high level of agreement between the methods (R2 = 0.9984 and 0.9951) for the quality control samples. The new system however was also capable of quantifying lower concentrations of both erlotinib and OSI-420 (0.5 and 0.1 ng/mL) with sufficient accuracy and precision. Along with the increased sensitivity we included the semi-quantitative determination of additional erlotinib metabolites M2, M3, M5, M6, M7, M8, M9, M10, M11, M12, M16 (hydroxy-erlotinib), M17, M18, M19, M20, M21 in a 0.1–1000 ng/mL range to the method. With a simple crash, dilute, and shoot sample preparation with acetonitrile and a 4.5 min analytical run time the method outperformed most other published methods in speed and simplicity and was suitable for TDM. Further, enhancement of the understanding of the pharmacokinetics of erlotinib and its metabolites was demonstrated.
中文翻译:
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液相色谱-串联质谱结合离子迁移率鉴定对厄洛替尼,其O-去甲基化代谢产物OSI-413和OSI-420以及其他代谢产物进行生物分析
厄洛替尼是用于治疗非小细胞肺癌的第一代上皮生长因子受体抑制剂。我们先前在Thermo TSQ Quantum Ultra三重四极杆质谱仪上发布的用于定量厄洛替尼,OSI-420和OSI-413以及其他一些激酶抑制剂的方法已转移到更敏感的Sciex QTRAP5500系统中。两种方法在以前的范围内(厄洛替尼和OSI-420的5–5000和1–1000 ng / mL)表现出可比的性能,并具有可比的准确度和精密度(98.9–106.2与98.7.0–104.0,以及3.7–13.4与4.6– 13.2),以及方法之间的高度一致性(R 2 = 0.9984和0.9951)。但是,新系统还能够以足够的精度和精确度定量测定较低浓度的厄洛替尼和OSI-420(0.5和0.1 ng / mL)。随着灵敏度的提高,我们还包括了其他厄洛替尼代谢物M2,M3,M5,M6,M7,M8,M9,M10,M11,M12,M16(羟基厄洛替尼),M17,M18,M18,M19,M20的半定量测定,方法中M21的浓度范围为0.1–1000 ng / mL。该方法使用乙腈进行简单的崩溃,稀释和射击样品制备,分析运行时间为4.5分钟,在速度和简便性方面均胜过大多数其他已发表方法,适用于TDM。此外,证明了对厄洛替尼及其代谢物的药代动力学的理解的增强。