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

The 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.