Wong Philip, Akrami Anna, Houk Brett, Vuu Irene, James Christopher A
Amgen Research, Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA 91320, USA.
Amgen Research, Clinical Pharmacology Modeling & Simulation, Thousand Oaks, CA 91320, USA.
Bioanalysis. 2022 Oct;14(19):1281-1292. doi: 10.4155/bio-2022-0173. Epub 2022 Dec 6.
Sotorasib (AMG 510) is a first-in-class KRAS inhibitor that received accelerated US FDA approval in 2021 for the treatment of patients with -mutated locally advanced or metastatic non-small-cell lung cancer. : An LC-MS/MS method was developed and validated for the determination of sotorasib in human plasma to support clinical development studies. Samples were prepared using protein precipitation and analyzed by LC-MS/MS using gradient elution with a calibration standard curve range of 10.0-10,000 ng/ml. Stable isotope labeled [C, D]-sotorasib was used as an internal standard. The method fully met FDA guidelines for all validation parameters, including precision, accuracy, selectivity, matrix effect, recovery and stability and has been extensively used to support multiple clinical studies.
索托拉西布（AMG 510）是一种首创的KRAS抑制剂，于2021年获得美国食品药品监督管理局（FDA）加速批准，用于治疗KRAS基因突变的局部晚期或转移性非小细胞肺癌患者。：开发并验证了一种液相色谱-串联质谱（LC-MS/MS）方法，用于测定人血浆中的索托拉西布，以支持临床开发研究。样品采用蛋白沉淀法制备，并通过LC-MS/MS进行分析，采用梯度洗脱，校准标准曲线范围为10.0 - 10,000 ng/ml。稳定同位素标记的[C,D]-索托拉西布用作内标。该方法在所有验证参数方面完全符合FDA指南，包括精密度、准确度、选择性、基质效应、回收率和稳定性，并且已广泛用于支持多项临床研究。
