Development of a multiple reaction monitoring (MRM) method based on high performance liquid chromatography/tandem mass spectrometry to analyze in vivo exposure profiles of complex herbal components independent of standards?

RSC Advances Pub Date: 2016-02-11 DOI: 10.1039/C5RA25389F

Abstract

Exposure profiles of herbal components in vivo play pivotal roles in pharmacodynamic evaluation. Herein, we report the development of a universal multiple reaction monitoring (MRM) method for the sensitive and accurate identification of in vivo exposure profiles of complex herbal systems, including exposure components, exposure times, and relative exposure levels. The method integrated multiple scan monitoring types based on high performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS), and mainly consisted of four steps: (a) analyzing herbal extract samples by high resolution mass spectrometry, (b) refining S-lens and CE voltages to develop the MRM method, (c) detecting exposure components, and (d) evaluating exposure times and levels. We applied this developed method step-by-step to delineate the flavonoid profiles of a Schisandra chinensis extract, detecting 22 exposure flavonoids of which 19 were defined as long-term exposure components. Using a “relative exposure approach”, relative exposure levels in vivo were further elucidated. Compared with the general method based on high resolution MS-based HPLC/linear trap quadrupole (LTQ)-Orbitrap, the improved method provided more comprehensive detection. Furthermore, we demonstrated the utility of this approach in the investigation of exposure profiles of pyridine alkaloids in a Tripterygium wilfordii Hook.F. extract. Of 55 MRM transitions, 39 exposure components were detected. The results of this study suggested that the improved method might provide an excellent foundation for sufficient, sensitive, and accurate monitoring of exposure profiles in complex herbal systems or homologous compounds in vivo.

Graphical abstract: Development of a multiple reaction monitoring (MRM) method based on high performance liquid chromatography/tandem mass spectrometry to analyze in vivo exposure profiles of complex herbal components independent of standards
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