Pharmacokinetic comparative study on salvianolic acid B in normal and hyperlipidemic rats based on microdialysis technique combined with liquid chromatography-mass spectrometry / 中草药

ABSTRACT

Objective: To study the pharmacokinetics of salvianolic acid B (Sal B) monomer in normal and hyperlipidemic rats. Methods: The hyperlipidemic rat model was replicated successfully by using high fat diet. The detection method for microdialysis samples was established by using LC-MS. The pharmacokinetic study on Sal B in normal and hyperlipidemic rats was carried out after ig administration with low-, medium-, and high-dose (25, 50, and 100 mg/kg) Sal B using microdialysis sampling technology. The microdialysis samples were corrected with in vivo recoveries and followed by LC-MS detection. The plasma drug concentration-time curves were established by the sampling time midpoint as timeline. The pharmacokinetic fitting parameters were obtained by using non-compartment model. Results: The LC-MS detection method was sensitive, specific, and able to meet the analytical requirements. The main pharmacokinetics parameters of normal rat after ig administration with low-, medium-, and high-dose Sal B were as follows Cmax were (38.551 ± 6.692), (95.550 ± 12.544), and (204.251 ± 20.342) ng/mL, respectively, tmax were (1.125 ± 0.000), (1.375 ± 0.125), and (1.125 ± 0.125) h, respectively, AUC0-t were (65.995 ± 12.367), (178.806 ± 33.592), and (422.836 ± 72.344) h∙ng/mL, respectively, MRT were (2.002 ± 0.061), (1.911 ± 0.042), and (1.955 ± 0.053) h, respectively; The main pharmacokinetics parameters of hyperlipidemia rats after ig administration with low-, medium- and high-dose Sal B were as follows Cmax were (49.265 ± 7.317), (113.986 ± 15.294), and (246.454 ± 30.476) ng/mL, tmax were (1.125 ± 0.000), (1.125 ± 0.125), and (1.375 ± 0.125) h, respectively, AUC0-t were (96.013 ± 15.384), (207.192 ± 32.676), and (486.843 ± 89.276) h∙ng/mL, respectively, MRT were (2.161 ± 0.049), (2.089 ± 0.033), and (2.097 ± 0.035) h, respectively. Conclusion: The LC-MS method is suitable for the analysis with the high sensitivity and strong specificity. The pharmacokinetics parameters of Sal B of hyperlipidemia rats, such as Cmax, AUC0-t, and MRT, are higher than those of normal rats, which is conducive to play a therapeutic role, but without statistical significance.