Bioanalysis of alectinib and metabolite M4 in human plasma, cross-validation and impact on PK assessment

被引：24

作者：

Heinig, Katja ^{[1
]}

Miya, Kazuhiro ^{[2
]}

Kamei, Tomonori ^{[2
]}

Guerini, Elena ^{[1
]}

Fraier, Daniela ^{[1
]}

Yu, Li ^{[3
]}

Bansal, Surendra ^{[3
]}

Morcos, Peter N. ^{[3
]}

机构：

[1] F Hoffmann La Roche & Co Ltd, Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev, Pharmaceut Sci, Grenzacherstr 124, CH-4070 Basel, Switzerland

[2] Chugai Pharmaceut Co Ltd, Kamakura Res Labs, 200 Kajiwara, Kamakura, Kanagawa 2478530, Japan

[3] F Hoffmann La Roche Ltd, Roche Innovat Ctr New York, Roche Pharmaceut Res & Early Dev, 430 East 29th St, New York, NY 10016 USA

来源：

BIOANALYSIS | 2016年 / 8卷 / 14期

关键词：

alectinib; Alecensa (R); anaplastic lymphoma kinase; column switching; cross-validation; LC-MS/MS; matrix effect; non-small-cell lung cancer; phospholipids; plasma; CELL LUNG-CANCER; ALK INHIBITOR ALECTINIB; SAMPLE PREPARATION; LC-MS/MS; ANTITUMOR-ACTIVITY; OPEN-LABEL; SUPPRESSION; METASTASES; CH5424802; AF-001JP;

D O I：

10.4155/bio-2016-0068

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: 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. Methods: 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. Conclusion: 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.

引用

页码：1465 / 1479

页数：15

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