The metabolism of YiGan San and subsequent pharmacokinetic evaluation of four metabolites in rat based on liquid chromatography with tandem mass spectrometry.

Abstract

A new method based on liquid chromatography-tandem time-of-flight mass spectrometry was developed to identify the metabolites in rat urine after oral administration of YiGan San (YGS). Eighteen prototype compounds and four metabolites named 11-hydroxyhirsuteine, 19-carbonylhirsutine, 19-carbonyl-dihydrocorynantheine, and 18-hydroxy-geissoschizine methyl ether were identified. Subsequently, a method of high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry was established for pharmacokinetic study of YGS in rat plasma. The concentration-time curves of four prototype compounds, senkyunolide I, ajmalicine, isocorynoxeine and rhynchophylline were constructed after an oral (9.1g YGS per kilogram of body weight) administration in rats. Method validation revealed excellent linearity over the range 220.00-0.55, 220.00-0.55, 21.40-0.05, and 19.80-0.05ng/mL for the four prototype compounds respectively. The stabilities results indicate that all of the analytes were stable in rat plasma in the autosampler for 24h, under freeze/thaw cycles (4 times in 24h), and at -20°C for one week. Residual analysis, heteroskedasticity test, and goodness-of-fit test were also performed to determine the accuracy of the linear regression method. The pharmacokinetic parameters were obtained. Four hours after administration, compound 11-hydroxyhirsuteine can be detected in rat plasma. Compared with purified ligustilide, YGS required a slightly longer period to reach maximum concentration (Cmax) in rat plasma.

• Authors: Yanan Gai, Han Chen, Wenyuan Liu, Feng Feng, Ning Xie
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 972 Pg. 22-8 (Dec 01 2014) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 25306115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Benzofurans
• Drugs, Chinese Herbal
• Indole Alkaloids
• Oxindoles
• Secologanin Tryptamine Alkaloids
• Yi-Gan San
• senkyunolide I
• corynoxeine
• rhyncophylline
• raubasine

Topics

• Animals
• Benzofurans (urine)
• Chromatography, High Pressure Liquid (methods)
• Drugs, Chinese Herbal (analysis, pharmacokinetics)
• Indole Alkaloids (urine)
• Male
• Oxindoles
• Rats
• Rats, Sprague-Dawley
• Secologanin Tryptamine Alkaloids (urine)
• Tandem Mass Spectrometry (methods)