Pharmacokinetics, tissue distribution, and excretion study of GL‐V9 and its glucuronide metabolite 5‐O‐glucuronide GL‐V9 in Sprague–Dawley rats

Author:

Zhang Xuefeng12,Liu Guanlan2,Sang Zechun2,Jin Xiaoxin3,Wang Yan4,Guo Qinglong1,Zhou Yuxin1ORCID,Song Xiuming5

Affiliation:

1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University Nanjing People’s Republic of China

2. TriApex Laboratories Co., Ltd Nanjing People’s Republic of China

3. Fushun No.12 Senior High School Fushun People’s Republic of China

4. Fushun No.2 Senior High School Fushun People’s Republic of China

5. TriApex (Nanjing) Clinical Research Co., LTD TriApex Laboratories Co., Ltd Nanjing People‘s Republic of China

Abstract

AbstractThe objective of this study is to explore the pharmacokinetics, tissue distribution, and excretion patterns of GL‐V9 and its glucuronide metabolite, 5‐O‐glucuronide GL‐V9, following the administration of GL‐V9 to Sprague–Dawley (SD) rats. In this research, we developed and validated rapid, sensitive, and selective ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) methods for quantifying GL‐V9 and 5‐O‐glucuronide GL‐V9 in various biological samples, including SD rat plasma, tissue homogenate, bile, urine, and feces. Quantification of GL‐V9 and 5‐O‐glucuronide GL‐V9 in plasma, tissue homogenate, bile, urine, and feces was performed using the validated LC–MS/MS methods. The bioavailability of GL‐V9 in SD rats ranged from 6.23% to 7.08%, and both GL‐V9 and 5‐O‐glucuronide GL‐V9 exhibited wide distribution and rapid elimination from tissues. The primary distribution tissues for GL‐V9 and 5‐O‐glucuronide GL‐V9 in rats were the duodenum, liver, and lung. GL‐V9 was predominantly excreted in urine, while 5‐O‐glucuronide GL‐V9 was primarily excreted in bile. GL‐V9 exhibited easy absorption and rapid conversion to its glucuronide metabolite, 5‐O‐glucuronide GL‐V9, following administration.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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