International Journal of Frontiers in Medicine, 2024, 6(4); doi: 10.25236/IJFM.2024.060404.
Lihua Qin1,2,3, Xiaoqun Duan1,2, Shu Zhang3, Meiqing Wang1,2,3, Xiaochuan Li3
1College of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541004, China
2College of Biomedical Industry, Guilin Medical University, Guilin, Guangxi, 541004, China
3Suzhou Xuhui Analysis Co., Ltd., No. 168 Yuanfeng Road, Kunshan, Jiangsu, 215300, China
VT198-2 is a new drug for the treatment of non-small cell lung cancer with KRAS G12 target. Ongoing clinical studies show that it has high safety and good clinical activity. Therefore, we developed a sensitive and reliable quantitative method of high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to study the pharmacokinetic characteristics of the new drug VT198-2 in rat plasma. Terfenadine was used as the internal standard, the protein precipitation method was adopted, ZORBAX Eclipse XDB-C18 column was used, and separation and detection were realized together with triple quadrupole mass spectrometer under basic chromatographic conditions. The accuracy and precision of this method are within the specified range. In this study, it was found that VT198-2 was stable in the plasma of SD rats, with good selectivity in the linear range of 0.295-295ng/mL, and the extraction recovery rate was between 98.7% and 99.6%, without matrix effect. The t1/2 of single intravenous and oral administration in rats was 2.02±0.01h and 2.8±1.1h, which resulted in the bioavailability of VT198-2 of 3.9%. Therefore, we believe that this method is specific, accurate and rapid, and it is suitable for the determination of VT198-2 plasma concentration in rats in preclinical research.
VT198-2, KRAS, G12C, LC-MS/MS, PK
Lihua Qin, Xiaoqun Duan, Shu Zhang, Meiqing Wang, Xiaochuan Li. Determination of VT198-2 in rat plasma by liquid chromatography-tandem mass spectrometry and its pharmacokinetics. International Journal of Frontiers in Medicine (2024), Vol. 6, Issue 4: 28-36. https://doi.org/10.25236/IJFM.2024.060404.
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