Simultaneous Determination And Pharmacokinetic Studies Of Five Water-soluble Components Of Danshen Injection In Animals

Objection To study the pharmacokinetics of Danshensu (DSS), Protocatechuic acid (ACID), Protocatechuic aldehyde (PAL), Salvianolic acid B (SAB) and Salvianolic acid A (SAA), five water-soluble components of Danshen Injection in animals.Methods A high performance liquid chromatography (HPLC)-UV method for simultaneous determination of DSS, ACID, PAL, SAB and SAA in animal plasma was developed after intravenously/intramuscularly administration of Danshen Injection. The pharmacokinetics parameters were calculated by 3P97 software.Results (1)HPLC method was proved to be simple, sensitive, highly specific and precise. The linear ranges were 50～8000 ng/ml (ACID, PAL), 100～8000 ng/ml(DSS,SAB), 200～8000 ng/ml(SAA)and the average recoveries were high. (2) After iv doses of Danshen Injection 2.5ml/kg(DSS 30.00mg/kg, ACID 2.25mg/kg, PAL 26.00mg/kg, SAB 5.50mg/kg, SAA 1.50mg/kg), 1.25 ml/kg (DSS 15.000mg/kg, ACID 1.125mg/kg, PAL 13.000mg/kg, SAB 2.750mg/kg, SAA 0.750mg/kg), 0.625 ml/kg(DSS 7.500mg/kg, ACID 0.562mg/kg, PAL 6.500mg/kg, SAB 1.375mg/kg, SAA 0.375mg/kg) to rabbits, the plasma concentration-time curves of DSS, ACID, PAL, SAB, SAA were fit to a two-compartment model and t1/2βwere 124.12～137.72min, 51.72～56.38min, 112.30～115.43min, 125.61～140.66min, 152.62～167.32min, CL were 5.4230～5.7760ml/kg/min, 18.2716～23.2757 ml/kg/min, 125.3682～150.8414ml/kg/min,15.0609～17.4459ml/kg/min,1.4206～1.5826ml/kg/min. There were no significant differences observed in the pharmacokineticparameters among the three different doses. (3) After iv dose of DanshenInjection 2.5ml/kg to rats, the plasma concentration-time curves of fivewater-soluble components were fit to a two-compartment model and t1/2βwere 125.73min, 55.92min, 157.42min, 112.82min, 199.49min, AUC were4999.44μg/ml·min, 107.86μg/ml·min, 141.24μg/ml·min, 451.33μg/ml·min,523.01μg/ml·min; After im dose of Danshen Injection 2.5ml/kg to rats, theplasma concentration-time curve of five water-soluble components were fitto a one-compartment model and t1/2Ke were 95.15min, 56.10min, 96.83min77.91min, 100.36min, AUC were 3234.06μg/ml·min, 53.74μg/ml·min,71.59μg/ml·min, 317.48μg/ml·min, 298.04μg/ml·min. (4) The bioavailability ofDSS, ACID, PAL, SAB, SAA were 64.59%, 49.83%, 50.69%, 70.34%, 56.99%.Conclusion This method appeared to be stable, sensitive andreproducible and it was successfully applied to the pharmacokinetic studyof five water-soluble components in animal plasma after intravenously orintramuscularly administration of Danshen Injection.