Pharmacokinetics and homeostatic impact of golden bile powder: evidence from surrogate analyte-based UPLC-MS/MS in...

Golden bile powder (GBP), an artificial bear bile powder, is used for liver protection and contains taurine-conjugated bile acids (BAs) with broad pharmacological activities. However, its pharmacokinetics and effects on endogenous BA homeostasis are unclear.

Sprague-Dawley rats received oral administration of GBP (54 mg/kg/day) combined with three deuterated taurine-conjugated BAs at fixed ratios for 7 days to facilitate separate analysis of changes in exogenous and endogenous BAs following administration. Single deuterated taurine-conjugated BA groups were also included. Blood samples were collected over a 24 h time window on days 1 and 7. We developed and validated a surrogate analyte-based UPLC-MS/MS method to quantify six BAs in rat plasma, eliminating endogenous interference. Pharmacokinetic parameters were obtained by non-compartmental analysis, and gender differences and accumulation effects were assessed using appropriate statistical comparisons.

The UPLC-MS/MS method demonstrated good linearity (r > 0.999), accuracy (89.1%-115%), precision (RSD < 15%), and stability (within ± 15%). Pharmacokinetic studies showed taurine-conjugated BAs in GBP had long half-lives (8.43-12.7 h) and gender-specific accumulation, with females displaying higher systemic exposure. For example, the AUC_0-24 h of TCA was approximately 16-fold higher in females than in males. Repeated GBP administration (54 mg/kg/day for 7 days) reshaped systemic BA composition, increasing both exogenous and endogenous BA concentrations, with the latter displaying more pronounced elevations-approximately fivefold higher than the exogenous BA AUC increase. Sex differences were evident, as female rats exhibited enhanced conversion of conjugated BAs to free forms. The BA shifts observed may be related to known enterohepatic circulation and gut microbiota-mediated BA transformation pathways.

This work establishes an analytical framework for evaluating endogenous and exogenous BA dynamics, contributing to future mechanistic and translational studies involving GBP and its potential applications.