Acta Pharmaceutica Sinica B 2015;5(3):246-253

doi:10.1016/j.apsb.2015.03.015

Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats.

Junke SONG 1 ; Wen ZHANG 1 ; Jialin SUN 2 ; Xiaona XU 1 ; Xue ZHANG 1 ; Li ZHANG 1 ; Zhangying FENG 3 ; Guan-Hua DU 1

Affiliations

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Keywords

AUC, the area under curve; Analysis method; Bioavailability; CI, confidence interval; CL, clearance; Cmax, peak plasma concentration; Danshen; Dose proportionality; ECE-1, endothelin converting enzyme 1; ESI, electrospray ionization; IS, internal standard; LC-MS; LLOQ, lower limit of quantification; Pharmacokinetics; QC, quality control; R.E., relative error; R.S.D., relative standard deviation; SIM, single ion monitoring; SalB, salvianolic acid B; SalD, salvianolic acid D; Salvia miltiorrhiza; Salvianolic acid D; TCM, traditional Chinese medicine; ULOQ, upper limit of quantification

Country

China

Language

English

Abstract

A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C 2min) were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (C max) was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0-t ) was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.