Development and validation of a liquid chromatography‐tandem mass spectrometry method for CPUL1, a novel antitumor candidate compound, and its application to pharmacokinetic studies

Autor: Yuanyuan Lu, Yanjun Zhang, Man Yuan, Jiaqin Chen, Yifan Xu, Qiong Jie, Zhilong An, Jianmin Liao, Yunxin Liu, Jun Li, Yubing Zhu, Jianjun Zou, Chun Ge, Dong Feng, Ying Wang
Rok vydání: 2022
Předmět:
Zdroj: Journal of Separation Science. 45:4397-4406
ISSN: 1615-9314
1615-9306
Popis: An active substance of pyrano[3,2-a]phenazine, also called CPUL1, is a synthesized phenazine derivative and displays broad-spectrum anticancer activities. Quantitative assessment of CPUL1 in biological samples has not been well established, hindering pharmaceutical development and application. According to international guidelines, a sensitive and selective liquid chromatography-tandem mass spectrometry method in negative ion mode was developed and validated for quantification of CPUL1 in human plasma, colorectal cancer cell lines, and rat plasma, whereby linearity and accuracy were demonstrated for the range of 1-1000 ng/ml. The validated liquid chromatography-tandem mass spectrometry method was successfully employed in pharmacokinetic studies of CPUL1 in vitro and in vivo. Notably, the cellular pharmacokinetic behavior of CPUL1 varies in colorectal cancer cell lines. Regarding the pharmacokinetic processes in vivo, oral absorption was less effective than an injection, with a bioavailability of 23.66%. CPUL1 was linearly eliminated after a single administration; however, it could accumulate in tissues (heart, liver, spleen, lung, and kidney) after multiple injections. In summary, this study established a capable bioanalytical method for CPUL1 and provided exploratory pharmacokinetic data, paving the way for use of this promising derivative in disease models.
Databáze: OpenAIRE
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