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An Effective and Sensitive HPLC–MS/MS Method for Determination of Cholic Acid-Coupled Camptothecin Derivative A2 in Rat Pharmacokinetics and Tissue Distribution

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Abstract

Camptothecin bile acid analog (A2) is a camptothecin derivative, which has been verified to possess the high anti-tumor activity. The purpose of this study was to develop an effective and sensitive detection method to investigate the pharmacokinetics, tissue distributions and the bioavailability in rat plasma and other organs for the further understanding of A2. The standard curves, control samples and quality control samples were prepared by blank plasma and tissues of non-administered mice at 4 °C for HPLC–MS/MS analysis. The method validation was carried out on the five different occasions (specificity and selectivity, linearity, accuracy and precision, extraction recovery and matrix effects, and stability). The pharmacokinetic analysis showed that A2 showed twice absorption at 1 h and 4 h after oral administration and the second absorption was stronger than the first absorption. A2 was distributed mainly in the intestine and spleen. A2 had great oral bioavailability and the potential targeting property, indicating that CPT coupled to bile acid groups helped to improve bioavailability by bile acid transporters. These results would promote the development of camptothecin-bile acid analogue.

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Funding

This work was supported by the China Postdoctoral Science Foundation (2022M712823), National Natural Science Foundation of China Grant (31270397) and Qianjiang talents projection Zhejiang province.

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Authors and Affiliations

  1. Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, College of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China

    Wenchao Wang, Xuyang Li, Lianhao An, Liuzhi Hu, ·Ruojiong Wang, Haonan Xiong, Xialin Hu, Xinyi Huang, Yewen Quan, Hong Wang & Qingyong Li

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  1. Wenchao Wang
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  2. Xuyang Li
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  3. Lianhao An
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Contributions

WW, XL, LA, RW and XH performed the research and interpreted the data. Preparation of the initial manuscript was carried out by WW, QL and LA. The manuscript was revised and approved by LA, RW, HX, XH, LH, XH and YQ, HW and QL contributed to the interpretation of the data and the writing and reviewing the manuscript. WW, LA, XH and LH contributed to the analysis and interpretation of the data.

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Correspondence to Qingyong Li.

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Confirm that there are no related financial or non-financial competing interests that need to be declared. The authors declare no conflicts of interest in this work.

Ethics Approval

Adult Sprague Dawley (SD) rats (female) weighting 200–220 g were obtained from the Laboratory Animal Center of Zhejiang Academy of Medical Sciences (Hangzhou, China; License No. SCXK [Zhe] 2019–0002). All animals were raised in a dedicated area with the room temperature and relative humidity kept at 25 ± 1 °C and 50%, respectively, and would adapt to the barrier environment for a week before treatment. All experiments were approved by the laboratory animals ethical committee of the Zhejiang University of Technology. The applied procedures comply with the ARRIVE guidelines and were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH publication No. 85–23, revised 1996). Rats were fasted overnight with free access to water before the experiment.

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Wang, W., Li, X., An, L. et al. An Effective and Sensitive HPLC–MS/MS Method for Determination of Cholic Acid-Coupled Camptothecin Derivative A2 in Rat Pharmacokinetics and Tissue Distribution. Chemistry Africa 7, 1373–1383 (2024). https://doi.org/10.1007/s42250-023-00846-6

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