International Journal of Frontiers in Medicine, 2023, 5(11); doi: 10.25236/IJFM.2023.051102.
Xuechao Yang1,2,4, Shu Zhang3,4, Xiaochuan Li2,4, Hongqian Qin4,5, Yang Yang1
1College of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541004, China
2College of Biomedical Industry, Guilin Medical University, Guilin, Guangxi, 541004, China
3School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, SAR, China
4Suzhou Xuhui Analysis Co., Ltd., No.168 Yuanfeng Road, Kunshan, Jiangsu, 215300, China
5School of Pharmacy, Yantai University, Yantai, Shandong, 264000, China
Although the target of KRAS G12C is no longer unbreakable, resistance to current drugs against KRAS G12C occurs. The emergence of a new drug, VT204, is expected to be a new clinical drug in this field. Preclinical pharmacokinetic (PK) studies in animal models during the formulation development phase provide preliminary evidence of the PK behaviour of a drug before clinical studies in humans and help to tailor the dosage form to the expected and necessary clinical behaviour. A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine VT204 in rat plasma. A single chromatographic run was performed on a ZORBAX Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm, Agilent) and at a flow rate of 0.75 mL·min-1. The intra- and inter-batch accuracies ranged from 95.3% to 103.3%, and the intra- and inter-batch precision did not exceed 15%. The t1/2 of single intravenous and oral administration in rats was 1.09±0.05 h and 1.47±0.55 h, which resulted in the bioavailability of VT204 of 63.52%. This method is accurate and specific and provides a good solution for the pharmacokinetic study of VT204 in rats.
VT204; KRAS G12C; Non-small cell lung cancer; LC-MS/MS; pharmacokinetic
Xuechao Yang, Shu Zhang, Xiaochuan Li, Hongqian Qin, Yang Yang. Quantification of VT204 in rat plasma by LC-MS/MS and its pharmacokinetic study. International Journal of Frontiers in Medicine (2023), Vol. 5, Issue 11: 10-16. https://doi.org/10.25236/IJFM.2023.051102.
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