RESUMO
A rapid sensitive analytical method was established and validated to investigate levistolide A in rat plasma by liquid chromatography-tandem mass spectrometry operated in the positive ion mode. Levistilide A (LA) and internal standard (IS) andrographolide (AD), mixed with the plasma sample, were separated on a reversed phase Spursil™ C18 5 µm column. The precursor/product transitions (m/z) were 398.5/381.3 for LA and (m/z) 368.0/351.1 for AD. The calibration curve was linear over the range from 5 to 1,250 ng/mL for oral administration and 10-4,000 for intravenous administration with a correlation coefficient (r) ≥0.9993. The lower limit of quantification was 5 ng/mL for LA in plasma. The inter- and intra-day accuracy and precision were less than ±15% of the relative standard deviation. In this study, the developed method is successfully applied to the comparative pharmacokinetic study of LA in rats after oral administration of LA alone, Rhizoma Chuanxiong, and Danggui-Shaoyao-San along with the bioavailability study of LA in rats. Our study shows that low bioavailability (7.5%) is observed after oral administration of LA. Traditional formula compatibility of Danggui-Shaoyao-San could significantly enhance LA bioavailability compared with LA alone and Rhizoma Chuanxiong.