Abstract
A rapid, sensitive and specific method for the simultaneous quantification of resibufogenin (RBG) and 3-epi-resibufogenin (3-ERBG) in rat plasma was developed by using a liquid–liquid extraction procedure and liquid chromatography–electrospray ionization/tandem mass spectrometric (LC–ESI–MS/MS) analysis. The separation was performed by HPLC on a reversed phase C18 HPLC column (150 × 2.1 mm, 3.5 μm) using a mobile phase of acetonitrilel-0.1% formic acid aqueous solution (45:55, v/v). The determination was performed by a triple-quadrupole mass spectrometer in the multiple reaction monitoring using positive mode of electrospray ionization (ESI). The calibration curves were both linear (R > 0.995) over the concentration range of 3.0–5,000 ng mL−1, and the lower limits of quantification were 3.0 ng mL−1 for both RBG and 3-ERBG. The intra-day and inter-day precisions (% RSD) were all less than 15%, and the accuracies (%RE) were within the range of ±15%. The mean recoveries of RBG, 3-ERBG and IS were over 82.7, 84.8 and 90.0% (n = 6), respectively. The method was proved to be rapid, sensitive and specific, and has been successfully applied to determine RBG and its major metabolite 3-ERBG in rat plasma after oral administration of RBG for pharmacokinetic study. Comparison of pharmacokinetic data with anti-tumor activities of RBG and ERBG suggested that 3-ERBG, as a major metabolite of RBG in rats, was perhaps also a bioactive form of RBG in vivo.
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Acknowledgments
We thank Education Department of Liaoning Province (LS2010059), Program for Liaoning Excellent Talents in University (LNET) and National Natural Science Foundation of China (30701088, 81073013 and 81160559) for financial support.
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H. Chen and S. Deng contributed equally to this work.
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Chen, H., Deng, S., Chang, P.R. et al. Simultaneous Determination of Resibufogenin and Its Major Metabolite 3-epi-Resibufogenin in Rat Plasma by HPLC Coupled with Tandem Mass Spectrometry. Chromatographia 75, 103–109 (2012). https://doi.org/10.1007/s10337-011-2165-5
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DOI: https://doi.org/10.1007/s10337-011-2165-5