Determination of Sennoside A in Rat Plasma by Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry and Its Application to a Rat Pharmacokinetic Study

Abstract

To characterize pharmacokinetic profile of sennoside A in rats after intravenous and oral administration, a simple and sensitive liquid chromatography tandem mass spectrometry method was established and validated for quantitative determination of sennoside A in rat plasma. After prepared by protein precipitation with acetonitrile, sennoside A and internal standard were separated on a Waters ACQUITY HSS T3 (2.1 × 100 mm, 1.8 μm) column using acetonitrile and 5-mM ammonium acetate in water as mobile phase by gradient elution. The method showed excellent linearity over the range of 0.5–1000 ng/mL with acceptable intra- and inter-day precision, accuracy, matrix effect, and recovery. The stability assay indicated that sennoside A was stable in plasma during the sample collection, preparation, and analysis. Next, the method was applied to pharmacokinetic study of sennoside A in rats. After intravenous and intragastric administrated to rats, the concentrations of sennoside A in plasma at different time points were quantitated and the pharmacokinetic parameters were calculated by software of DAS 2.0. Pharmacokinetic parameters suggested that after oral administration, sennoside A was reached to the peak at 2.9–3.6 h with a C_max value of 13.2–31.7 ng/mL. Sennoside A was eliminated slowly from the plasma with T_1/2 value between 15.4 and 18.3 h. The oral absolute bioavailability was among 0.9%–1.3%, which indicated low blood exposure level.