Heinig Katja, Miya Kazuhiro, Kamei Tomonori, Guerini Elena, Fraier Daniela, Yu Li, Bansal Surendra, Morcos Peter N
Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara Kamakura Kanagawa, 247-8530 Japan.
Bioanalysis. 2016 Jul;8(14):1465-79. doi: 10.4155/bio-2016-0068. Epub 2016 Jun 22.
Alectinib is a novel anaplastic lymphoma kinase (ALK) inhibitor for treatment of patients with ALK-positive non-small-cell lung cancer who have progressed on or are intolerant to crizotinib. To support clinical development, concentrations of alectinib and metabolite M4 were determined in plasma from patients and healthy subjects.
LC-MS/MS methods were developed and validated in two different laboratories: Chugai used separate assays for alectinib and M4 in a pivotal Phase I/II study while Roche established a simultaneous assay for both analytes for another pivotal study and all other studies.
Cross-validation assessment revealed a bias between the two bioanalytical laboratories, which was confirmed with the clinical PK data between both pivotal studies using the different bioanalytical methods.
阿来替尼是一种新型间变性淋巴瘤激酶（ALK）抑制剂，用于治疗对克唑替尼进展或不耐受的ALK阳性非小细胞肺癌患者。为支持临床开发，在患者和健康受试者的血浆中测定了阿来替尼及其代谢物M4的浓度。
在两个不同实验室开发并验证了液相色谱-串联质谱（LC-MS/MS）方法：中外制药在一项关键的I/II期研究中对阿来替尼和M4使用单独的测定方法，而罗氏为另一项关键研究和所有其他研究建立了两种分析物的同时测定方法。
交叉验证评估显示两个生物分析实验室之间存在偏差，这在两项使用不同生物分析方法的关键研究之间的临床药代动力学数据中得到证实。
