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

Abstract

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%.

LC‐MS/MS determination of bakkenolide D in rats plasma and its application in pharmacokinetic studies

“…The oral bioavailability calculated by (AUC p.o./dose )/(AUC i.v./dose ) of BD in rats was about 2.57%. Our previous study showed that the oral bioavailability of BA in rats at 20 mg/kg was 15.7% (Pei et al, 2012). Thus, BA and BD demonstrated different pharmacokinetic profiles.…”

“…In our previous work, the bakkenolide A (BA) was selected for its representative skeleton structure of bakkenolide sesquiterpene, and a sensitive LC-MS/MS analytical method has been established to determine the BA in rat plasma. The oral bioavailability of BA in rats at 20 mg/kg is 15.7% (Pei et al, 2012). More recently, we have isolated a sufficient amount of bakkenolide D (BD) from the dried rhizome of P. japonicas.…”

Bakkenolide‑IIIa ameliorates lipopolysaccharide‑induced inflammatory injury in human umbilical vein endothelial cells by upregulating LINC00294

“…et Zucc.) F. Schmidt and Petasites tricholobus Franch (8), which have been used in Chinese folk medicine to treat palsy, hypertension, cough and snakebite for hundreds of years (9). Compared with three other bakkenolides, bakkenolide-IIIa (Bak-IIIa), which is an important active component of bakkenolides, has been reported to display the best neuroprotective effect against oxygen-glucose deprivation-induced neuronal injuries (9).…”

Development and validation of a UPLC–MS/MS method for determination of Sarsasapogenin‐AA22 in rat plasma and its application to a pharmacokinetic study

“…To determine the concentration of the compound AA22 in rat plasma, a sensitive, accurate and robust quantification method was established and validated in this study using liquid chromatography–tandem mass spectrometry (LC–MS/MS). LC–MS/MS is one of the most frequently adopted methods for pharmacokinetic studies owing to its high sensitivity and selectivity (Bao, Wang, & Tang, ; Pei et al, ; Ramakrishna et al, ). In addition, an easy and convenient protein precipitation process for pre‐treatment and short chromatographic run by LC/MS/MS (6 min) increased the throughput for the pharmacokinetics research.…”