期刊
ANALYST
卷 147, 期 6, 页码 1175-1180出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1an01928g
关键词
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资金
- Scientific Research Foundation of Capital Medical University [PYZ20022]
- National Natural Science Foundation of China [81703611]
- Beijing Municipal Natural Science Foundation [7164262]
- Beijing Municipal Administration of Hospitals' Youth Program [QML20180305]
MRTX849 is a novel targeted inhibitor of KRAS (G12C) that improves the response rate in patients with advanced solid tumors. This study reports an analytical HPLC-MS/MS assay and pharmacokinetics for MRTX849 in plasma, demonstrating the accuracy and validity of the method.
MRTX849 is a novel, highly selective, targeted inhibitor of KRAS (G12C), which significantly improves the objective response rate in patients with advanced solid tumors. However, neither an analytical HPLC-MS/MS assay nor pharmacokinetics has been reported for MRTX849 in plasma. In the present study, chromatography was accomplished on a reversed phase C-18 column (50 x 2.1 mm, 3.5 mu m). The limit of detection of MRTX849 was 0.02 ng mL(-1) at S/N >= 3. Only 20 mu L of plasma was utilized for accurate quantitation. The optimized analytical assay was fully validated and verified in accordance with guidelines. The calibration curve for MRTX849 was linear with a correlation coefficient >0.99 in the range of 0.05-200 ng mL(-1). The intra- and inter-day accuracy and precision were all within +/- 10%. The matrix effect and recovery were consistent and acceptable under several quality control concentrations. This HPLC-MS/MS method was successfully applied for a pharmacokinetic study of MRTX849 at a dose of 15 mg kg(-1).
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