Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study.

A sensitive rapid analytical method was established and validated to determine the bakkenolide A (BA) in rat plasma. This method was further applied to assess the pharmacokinetics of BA in rats receiving a single dose of BA. Liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode was used in the method, and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The combination of a simple sample cleanup and short chromatographic running time (2.4?min) increased the throughput of the method substantially. The method was validated over the range of 11000?ng/mL with a correlation coefficient?>?0.99. The lower limit of quantification was 1?ng/mL for BA in plasma. Intra- and inter-day accuracies for BA were 93112% and 103104%, respectively, and the inter-day precision was less than 15%. After a single oral dose of 20?mg/kg of BA, the mean peak plasma concentration (Cmax) of BA was 234.7?+/-?161?ng/mL at 0.25?h. The area under the plasma concentrationtime curve (AUC024 h) was 535.8?+/-?223.7?h.ng/mL, and the elimination half-life (T1/2) was 5.0?+/-?0.36?h. In case of intravenous administration of BA at a dosage of 2?mg/kg, the area under the plasma concentrationtime curve (AUC024 h) was 342?+/-?98 h.ng/mL, and the elimination half-life (T1/2) was 5.8?+/-?0.7?h. Based on the results, the oral bioavailability of BA in rats at 20?mg/kg is 15.7%. Copyright (c) 2012 John Wiley & Sons, Ltd.