Pharmacokinetics and in vitro liver microsomal enzyme metabolism of Xylopic acid

Abstract

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 determination 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.