Simultaneous determination of senecionine, adonifoline and their metabolites in rat serum by UPLC–ESIMS and its application in pharmacokinetic studies

Aizhen Xiong, Yan Li, Li Yang, Jiangguo Gao, Yuqi He, Changhong Wang, Zhengtao Wang, Aizhen Xiong, Yan Li, Li Yang, Jiangguo Gao, Yuqi He, Changhong Wang, Zhengtao Wang

Index: J. Pharm. Biomed. Anal. 50(5) , 1070-4, (2009)

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Abstract

A rapid, selective and sensitive ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–ESIMS) method was firstly developed and validated for the simultaneous determination of two hepatotoxic pyrrolizidine alkaloids (HPAs), senecionine (SEN), adonifoline (ADO), and their N-oxides (SENNOX and ADONOX), the main metabolites in rat serum. The whole analysis was achieved within 4.5 min by gradient elution on an ACQUITY UPLC BEH C18 column (50 mm × 2.1 mm, i.d. 1.7 μm) following a solid phase extraction for serum samples. Good linearity was achieved using weighted (1/ x 2) least squares linear regression over a 1600-fold dynamic range for SEN and ADO (LLOQ was about 0.006 μg/ml) and 800-fold dynamic range for SENNOX and ADONOX (LLOQ was about 0.012 μg/ml). The R.S.D. of intra- and inter-day precision was below 4.91% and 11.15% respectively, while the R.E. of accuracy was within 4.52%, 6.81%, 2.69%, and 7.12% for SEN, SENNOX, ADO, and ADONOX, respectively. The developed method was successfully applied to the in vivo pharmacokinetic study in rats after intravenous administration of SEN and ADO.