Pharmacokinetics and in vitro liver microsomal enzyme metabolism of Xylopic acid

Xylopic acid (XA) is a bioactive diterpene kaurene isolate of the Guinea pepper fruit, Xylopia aethiopica (Annonaceae) with numerous well-established biological effects. In this study, we aimed to fill certain scientific voids in terms of the scientific literature on XA, specifically, its pharmacokinetic (PK) parameters and in vitro liver microsomal enzyme metabolism. A new LC-MS/MS method was developed and validated for the deter-mination of the plasma concentration-time profile of XA. The method was found to be accurate, precise, selective and repeatable with lowest limit of quantification (LLOQ) of 10 ng/mL and run time of 15 min. The maximum plasma concentration (Cmax), time at which maximum plasma concentration was attained (Tmax), half-life (t1/2), clearance (CL) and mean residence time (MRT) of XA were 167.03 +/- 6.18 ng/mL; 10 h; 13.03 +/- 7.33 h; 0.04 +/- 0.01 mL/h/kg and 23.83 +/- 11.02 h respectively. Six metabolites (M1-M6) were tentatively identified after XA was subjected to in vitro liver microsomal enzyme metabolism. The metabolites were the products of methylation (M1), glucuronidation (M2), deacetylation (M3), glucosylation (M4), hydroxylation and glutamic acid addition (M5) and glutathionylation (M6). The outcome of this study provides useful insights that could guide further research on XA.

Automated summary

This study aimed to address the lack of scientific literature on xylopic acid (XA) by investigating its pharmacokinetic parameters and in vitro liver microsomal enzyme metabolism. A new LC-MS/MS method was developed and validated for determining the plasma concentration-time profile of XA, and six metabolites were identified after XA underwent liver microsomal enzyme metabolism. The results of this study provide valuable insights for further research on XA.