A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry

Abstract

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid-liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95-113 and 98-107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration-time curve (AUC0-12 h) was 698 +/- 129 ng.h/mL, and the elimination half-life (T1/2) was 3.29 h.

Some pharmacokinetic parameters of salvianolic acid A following single-dose oral administration to rats

“…Currently, there are only two reports regarding the pharmacokinetics of Sal A after oral administration in pure form; one in Sprague-Dawley rats (Pei et al. 2008 ) and the other in Beagle dogs (Sun et al. 2013 ).…”

Salvianolic acids: small compounds with multiple mechanisms for cardiovascular protection

“…By intravenous injection, 100 mg/kg Sal B reaches the maximal plasma concentration ( C max ) around 910 μg/ml, and the half life ( t 1/2 ) of Sal B is around 105 minutes [7]. For oral administration, the C max of 500 mg/kg Sal B is 1.5 μg/ml while 100 mg/kg Sal A is only 308 ng/ml; the t 1/2 is around 248 minutes for Sal B and 3.29 hours for Sal A [7,9]. The oral bioavailability of Sal B in a conscious rat is calculated to be 2.3% [7], which is higher than rats under general anesthesia reported by Zhang et al [10].…”

Alleviatory effects of Danshen, Salvianolic acid A and Salvianolic acid B on PC12 neuronal cells andDrosophila melanogastermodel of Alzheimer’s disease

“…However, it provided the least protection when fed to a whole organism and this could be due to its incomplete cellular absorption compared to SalB. This difference in absorption was previously demonstrated in rats whereby oral administration of SalA showed a significantly lower plasma concentration of only 308 ng/ml compared to SalB which reached 1.5 μg/ml (Y. T. Wu et al, 2006, Pei et al, 2008. The UPLC findings from this study further supported this claim with the concentration of SalB found in the brains of DWE-fed flies being three times more than that of SalA.…”

“…It also raised the likelihood that SalA and SalB were utilized by neurons in live organisms. However, there were undetectable levels of SalA and SalB in the heads, bodies and faeces which could be due to their short half-life (Pei et al, 2008, Y. T. Wu et al, 2006.…”