Welcome to Francis Academic Press

International Journal of Frontiers in Medicine, 2023, 5(11); doi: 10.25236/IJFM.2023.051102.

Quantification of VT204 in rat plasma by LC-MS/MS and its pharmacokinetic study


Xuechao Yang1,2,4, Shu Zhang3,4, Xiaochuan Li2,4, Hongqian Qin4,5, Yang Yang1

Corresponding Author:
Yang Yang

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

Cite This Paper

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.


[1] L. Huang, Z. Guo, F. Wang, L. Fu, KRAS mutation: from undruggable to druggable in cancer, Signal Transduct Target Ther 6 (2021) 386. 10.1038/s41392-021-00780-4.

[2] J.B.E. Janssen, J.P. Medema, E.C. Gootjes, D.V.F. Tauriello, H.M.W. Verheul, Mutant RAS and the tumor microenvironment as dual therapeutic targets for advanced colorectal cancer, Cancer Treat Rev 109 (2022) 102433. 10.1016/j.ctrv.2022.102433.

[3] A.R. Moore, S.C. Rosenberg, F. McCormick, S. Malek, RAS-targeted therapies: is the undruggable drugged?, Nat Rev Drug Discov 19 (2020) 533-552. 10.1038/s41573-020-0068-6.

[4] J. Canon, K. Rex, A.Y. Saiki, C. Mohr, K. Cooke, D. Bagal, K. Gaida, T. Holt, C.G. Knutson, N. Koppada, B.A. Lanman, J. Werner, A.S. Rapaport, T. San Miguel, R. Ortiz, T. Osgood, J.R. Sun, X. Zhu, J.D. McCarter, L.P. Volak, B.E. Houk, M.G. Fakih, B.H. O'Neil, T.J. Price, G.S. Falchook, J. Desai, J. Kuo, R. Govindan, D.S. Hong, W. Ouyang, H. Henary, T. Arvedson, V.J. Cee, J.R. Lipford, The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity, Nature 575 (2019) 217-223. 10.1038/s41586-019-1694-1.

[5] D. Tang, G. Kroemer, R. Kang, Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges, Mol Cancer 20 (2021) 128. 10.1186/s12943-021-01422-7.

[6] Z. Han, D. Zhou, J. Wang, B. Jiang, X. Liu, Reflections on drug resistance to KRAS(G12C) inhibitors and gene silencing/editing tools for targeting mutant KRAS in cancer treatment, Biochim Biophys Acta Rev Cancer 1877 (2022) 188677. 10.1016/j.bbcan.2022.188677.

[7] A. Ghimessy, P. Radeczky, V. Laszlo, B. Hegedus, F. Renyi-Vamos, J. Fillinger, W. Klepetko, C. Lang, B. Dome, Z. Megyesfalvi, Current therapy of KRAS-mutant lung cancer, Cancer Metastasis Rev 39 (2020) 1159-1177. 10.1007/s10555-020-09903-9.

[8] F. McCormick, Sticking it to KRAS: Covalent Inhibitors Enter the Clinic, Cancer Cell 37 (2020) 3-4. 10.1016/j.ccell.2019.12.009.

[9] M. Sattler, A. Mohanty, P. Kulkarni, R. Salgia, Precision oncology provides opportunities for targeting KRAS-inhibitor resistance, Trends in Cancer (2022). 10.1016/j.trecan.2022.10.001.

[10] H.J. Cho, H.J. Jung, Cyclophilin A Inhibitors Suppress Proliferation and Induce Apoptosis of MKN45 Gastric Cancer Stem-like Cells by Regulating CypA/CD147-Mediated Signaling Pathway, International journal of molecular sciences 24 (2023). 10.3390/ijms24054734.