Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC‐QTOF‐MS/MS and LC‐TQ‐MS/MS

Abstract

Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC-QTOF-MS/MS and LC-TQ-MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action.

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

“…The plasma concentration of an orally administered DG reached C max (132:5 ± 48:2 ng/mL) at 5:01 ± 0:55 h with an AUC of 4121:9 ± 1354:7 ng • h/mL and an absolute oral bioavailability of 4:45 ± 1:46% [32,33]. Similarly, Liu et al have demonstrated that treatment with DG resulted in a C max of 42:1 ± 30:4 ng/mL at 11:3 ± 3:9 h along with an AUC 0-60 h of 1309:3 ± 849:8 ng h/mL and t 1/2 of 10:4 ± 4:2 h [48]. It was suggested that a single dosage of DG administered to rats, monkeys, and dogs was mostly excreted into feces, while the amount absorbed was rapidly eliminated via bile.…”

Effects of Lactobacillus plantarum FZU3013-Fermented Laminaria japonica on Lipid Metabolism and Gut Microbiota in Hyperlipidaemic Rats

“…Metabolomic analysis can detect changes in metabolism under different stimuli by analyzing the changes in endogenous small molecule metabolites ( 23 ). A previous study applied ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) for serum metabolomics and showed that the levels of amino acids and BAs are closely related to the occurrence and development of hyperlipidaemia ( 24 , 25 ). However, there have been no reports on the mechanism of action of LPLJ supplementation in liver metabolomics based on UHPLC-QTOF/MS in patients with hyperlipidaemia.…”

Development and validation of a rapid and sensitive LC–MS/MS method for the determination of polyphyllin II in rat plasma and its application in a pharmacokinetic study

“…According to the literature, several analytical methods using LC–MS/MS for quantification of steroidal saponins in complicated biological samples have been published so far (Wu, Zhang, Xu, et al, ; Wu, Zhang, Zhang, Xu, & Wang, ; Liu, Zhu, Shakya, & Wu, ; Yang et al, ), yet these methods either have low sensitivity or require a longer analysis time for sample analysis. In addition, in a previous study of method development for quantification of steroidal saponins (Yin, Qu, Zhang, et al, ; Yin, Qu, Li, et al, ), the sample preparation was time consuming.…”