Academic Journal of Medicine & Health Sciences, 2025, 6(9); doi: 10.25236/AJMHS.2025.060912.
Yanfang Zhang1, Yujie Li3, Shu Zhang3, Xiaochuan Li3, Xiaoqun Duan1,2
1College of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541000, China
2College of Biomedical Industry, Guilin Medical University, Guilin, Guangxi, 541004, China
3Suzhou Xuhui Testing Co., Ltd., Kunshan, Jiangsu, 215300, China
By employing equilibrium dialysis combined with high-performance liquid chromatography- tandem mass spectrometry (HPLC-MS/MS) to determine the plasma protein binding rates of KRAS-G12C inhibitor VT204 across five species (human, cynomolgus monkey, beagle, rat and mouse) and compare their differences. Additionally, validated HPLC-MS/MS methods were used to investigate the tissue distribution of VT204 in tumor-bearing mice. The results demonstrated: At three test concentrations (1, 3, and 10μmol/L), human, cynomolgus monkey, and beagle exhibited plasma protein binding rates exceeding 95%. In contrast, rats (at 3μmol/L and 10μmol/L) and mice (at 1μmol/L) showed binding rates below 95.0%. Following intragastric administration of VT204 at 20 mg/kg, the compound distributed widely across all tested tissues, with peak concentrations achieved 1 hour post-administration. The tissue distribution profile (in descending order of concentration) was: small intestine > liver > tumor > kidney > heart > lung > spleen > brain.
KRAS-G12C; VT204; protein binding rate; HPLC-MS/MS
Yanfang Zhang, Yujie Li, Shu Zhang, Xiaochuan Li, Xiaoqun Duan. VT204 in Vitro Protein Binding and Tissue Distribution Study. Academic Journal of Medicine & Health Sciences (2025), Vol. 6, Issue 9: 79-85. https://doi.org/10.25236/AJMHS.2025.060912.
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