Studies On The Chemical Constituents Of Aconitum Carmichaeli Debx. And Veratrum Nigrum Linn. Imcompatibility By LC/MS Technologies

Objective: To study the chemical constituents of Aconitum Carmichaeli Debx. and Veratrum nigrum Linn. imcompatibility.Methods: In the present study, an ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOFMS) based chemical profiling approach to rapidly evaluate chemical diversity after co-decocting of the incompatible pairs of Aconitum Carmichaeli Debx. and Veratrum nigrum Linn.. Two different kinds of decoctions, namely mixed decoction: mixed water extract of each individual herbs, and co-decoction: water extract of mixed two constituent herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC/Q-TOFMS analysis, the datasets of tR-m/z pairs, ion intensities and sample codes were processed with supervised orthogonal partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between these two kinds of decoction samples. Once a clear classification trend was found in score plot, extended statistical analysis was performed to generate S-plot, in which the variables (tR-m/z pair) contributing most to the difference were clearly depicted as points at the two ends of"S", and the components that correlate to these ions were regarded as the most changed components during co-decocting of the incompatible pair. The identities of the changed components can be identified by comparing the retention times and mass spectra with those of reference compounds and/or tentatively assigned by matching empirical molecular formulae with those of the known compounds published in the literatures. Using the proposed approach, global chemical difference was found between mixed decoction and co-decoction, and diester diterpenoid alkaloids eg. aconitine, mesaconitine, hypaconitine, 10-OH-aconitine, 10-OH-mesaconitine, and deoxyaconitine were identified as the most changed toxic components of the incompatible pairs of Aconitum Carmichaeli Debx. and veratrum steroid alkaloids were identified as the most changed toxic components of the incompatible pairs of Veratrum nigrum Linn. during co-decocting. It is suggested that this newly established approach could be used to practically reveal the possible toxic components changed/increased of the herbal combination taboos, e.g. the Eighteen Incompatible Medications (Shi Ba Fan), in traditional Chinese medicines.Results: Rrsult shows significant difference between two kinds of decoction samples, and the diester diterpenoid alkaloids (DDAs) eg. aconitine, mesaconitine, hypaconitine, 10-OH-aconitine, 10-OH-mesaconitine, and deoxyaconitine were identified as the most changed/increased toxic components of the incompatible pairs of Aconitum Carmichaeli Debx. and veratrum steroid alkaloids (VSAs) eg. jervine, pseudojervine, rubijervine, deoxyjervine, angeloylzygadenine, veratroylzygadenine, veratridine were identified as the most changed/increased toxic components of the incompatible pairs of Veratrum nigrum Linn. during co-decocting; Developed an exact mass search software EMS based on the MassLynx workstation. By the EMS module, high performance mass library for traditional Chinese medicine chemical constituents identification was established on quadrupole time of flight mass spectrometry with electrospray ionization interface to improve the efficiency and accuracy of ingredients identification in qualitative analysis.Conclusion:1,Diester diterpenoid alkaloids (DDAs) were identified as the most increased toxic components of the incompatible pairs of Aconitum Carmichaeli Debx.2,Veratrum steroid alkaloids (VSAs) were identified as the most increased toxic components of the incompatible pairs of Veratrum nigrum Linn.3,By the EMS module, high performance mass library was established to improve the efficiency and accuracy of ingredients identification in qualitative analysis.