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 1-1000 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 93-112% and 103-104%, 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 (C(max) ) of BA was 234.7 ± 161 ng/mL at 0.25 h. The area under the plasma concentration-time curve (AUC(0-24 h) ) was 535.8 ± 223.7 h·ng/mL, and the elimination half-life (T(1/2) ) 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 concentration-time curve (AUC(0-24 h) ) was 342 ± 98 h⋅ng/mL, and the elimination half-life (T(1/2) ) was 5.8 ± 0.7 h. Based on the results, the oral bioavailability of BA in rats at 20 mg/kg is 15.7%.
Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Lixia
L
Pei
Dongmei
D
Dai
Yuanwu
Y
Bao
Feng
F
Chen
Jin
J
Zheng
Ji
J
Li
Sheng
S
Liu
Xiuping
X
Chen
D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D016018:Least-Squares Analysis; D008297:Male; D000432:Methanol; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D007783:Lactones
D000432:Methanol; D012717:Sesquiterpenes; C002602:costunolide; D007783:Lactones; C016257:bakkenolide A