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

Lixia Pei, Dongmei Dai, Yuanwu Bao, Feng Chen, Jin Zheng, Ji Li, Sheng Liu, Xiuping Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (Cmax) 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 (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 concentration-time curve (AUC0-24 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%.

Original languageEnglish (US)
Pages (from-to)962-968
Number of pages7
JournalJournal of Mass Spectrometry
Volume47
Issue number8
DOIs
StatePublished - Aug 1 2012

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Pharmacokinetics
Liquid chromatography
Mass spectrometry
Rats
Plasmas
bakkenolide A
Methanol
Throughput
Monitoring

All Science Journal Classification (ASJC) codes

  • Spectroscopy

Cite this

Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study. / Pei, Lixia; Dai, Dongmei; Bao, Yuanwu; Chen, Feng; Zheng, Jin; Li, Ji; Liu, Sheng; Chen, Xiuping.

In: Journal of Mass Spectrometry, Vol. 47, No. 8, 01.08.2012, p. 962-968.

Research output: Contribution to journalArticle

Pei, Lixia ; Dai, Dongmei ; Bao, Yuanwu ; Chen, Feng ; Zheng, Jin ; Li, Ji ; Liu, Sheng ; Chen, Xiuping. / Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study. In: Journal of Mass Spectrometry. 2012 ; Vol. 47, No. 8. pp. 962-968.
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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 (Cmax) 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 (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 concentration-time curve (AUC0-24 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{\%}.",
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AU - Zheng, Jin

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N2 - 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 (Cmax) 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 (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 concentration-time curve (AUC0-24 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%.

AB - 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 (Cmax) 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 (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 concentration-time curve (AUC0-24 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%.

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