Comparative Study of Pharmacokinetics and Renal Exposure of Salvianolic Acid B and Its Metabolite Danshensu in Normal and Renal Fibrosis Mice

ABSTRACT Salvianolic acid B (SAB), a water‐soluble compound in Salvia miltiorrhiza (Danshen), has been widely used in the treatment of renal fibrosis. This study aimed to investigate the pharmacokinetics of SAB and its active metabolite danshensu (DSS) after intraperitoneal injection of Salvia miltiorrhiza depside salt for injection (SDSI) or SAB in normal and unilateral ureteric obstruction (UUO) mice. An LC‐MS/MS method was developed to simultaneously determine the SAB and DSS in biological samples. The validation results showed that the linearity, accuracy and precision, matrix effects and recovery, and stability satisfied the FDA bioanalysis guidelines. Pharmacokinetic study showed that plasma and renal exposure of SAB in mice administered SAB were higher than that in mice administered SDSI in the sham group, while those of DSS were lower. Compared with the sham group, the AUC 0‐t of SAB in obstructed kidneys (OKs) and non‐obstructed kidneys (NOKs) of the UUO group decreased by 71.14% and 54.63%, respectively. The AUC 0‐t of DSS in the OKs and NOKs of the UUO group increased by 60.8% and 177.79%, respectively, compared with the sham group. Developed method was successfully applied to the bioanalysis of SAB and DSS. Our study provides pharmacokinetic support for the rational clinical application of SAB.