Global Detection and Identification of Nontarget Components from Herbal Preparations by Liquid Chromatography Hybrid Ion Trap Time-of-Flight Mass Spectrometry and a Strategy

Abstract

Although the current literature has recorded many reports of identifying components from herbal preparations, all of them were largely limited to target components. This paper provides a novel and generally applicable approach to identifying nontarget components from herbal preparations, based on the use of liquid chromatography ion trap time-of-flight mass spectrometry (LC/MS-IT-TOF). A simple program was originally developed for searching the common diagnostic ions from all experimentally generated ions. The components sharing the exact same ions (mass error < 5 mDa) were classified into a family. All families were then connected into a coherent network by the bridging components that are present in two or more families. With the benefit from such a network, it is feasible to sequentially characterize the structures of all diagnostic ions once a single component has been de novo identified. The structures of the diagnostic ions could then be used as "a priori" information for selecting the exact candidates containing the substructures of the corresponding diagnostic ions from the primary database hits. This strategy enables a nearly 7-fold narrowing of the database hits and thus substantially enhances the analytical efficiency and sharpness. With the use of such an approach, 43 out of 53 components incorporated into the network have been successfully identified from the test herbal preparation. For the rest, components failed to be identified using this approach; a complementary approach to screening by sequential loss of specific chemical groups, proposed from the accurate mass differences between fragments, was established to narrow the database hits. All of the 87 peaks detected have been successfully identified by combining the use of both approaches except failed to differentiate some isomers. The presently developed approach and methodology would be useful for the identifications of complicated nontarget components from various complex mixtures such as herbal preparations, biological, and environmental samples.

Microsomal Cytochrome P450-Mediated Metabolism of Protopanaxatriol Ginsenosides: Metabolite Profile, Reaction Phenotyping, and Structure-Metabolism Relationship

“…On the basis of a powerful LC/MS-IT-TOF analysis that had been well developed in our laboratory for identification of multiple compounds from a complex matrix a A panel of 10 recombinant human P450 isoforms was screened, and only CYP3A4 and, to a very minor extent, CYP3A5 were found to be active toward the oxygenation metabolism of PPT-type ginsenosides. (Hao et al, 2008a;Zheng et al, 2009), three monooxygenated metabolites for each of the PPT ginsenosides and three monooxygenated and three double-oxygenated metabolites for the aglycone PPT were identified from the microsomal incubation media. As seen from the fragment patterns of both parent compounds and metabolites, the oxygenation metabolism site on the C20 aliphatic branch chain was proposed.…”

Development of a Systematic Approach to Identify Metabolites for Herbal Homologs Based on Liquid Chromatography Hybrid Ion Trap Time-of-Flight Mass Spectrometry: Gender-Related Difference in Metabolism of SchisandraLignans in Rats

“…Among them, the newly developed hybrid ion trap and time-of-flight mass spectrometry (IT-TOF/MS) was selected for its unmatched sensitivity, accuracy, resolution, and high throughput for the identification of complex compounds in addition to its excellent MS n function (Hao et al, 2008;Zheng et al, 2009). Liquid chromatography-hybrid ion trap and time-of-flight mass spectrometry (LC-IT-TOF/MS) has been successfully applied to the global identification of target and nontarget components in Shengmai and Mai-Luo-Ning injection, as well as identification of several drug metabolites (Hao et al, 2008;Zheng et al, 2009).…”

Metabolism of cyadox in rat, chicken and pig liver microsomes and identification of metabolites by accurate mass measurements using electrospray ionization hybrid ion trap/time‐of‐flight mass spectrometry

“…Moreover, multiple scans of metabolites in MS and MS 2 modes and accurate mass measurements can be automatically performed simultaneously through data-dependent acquisition. There are also literature reports on identification of components from herbal preparations and drug metabolites using LC/MS-ITTOF, 13,14 demonstrating the power of this technology for providing accurate mass measurements in structural assignments. The aim of the present study was to investigate the metabolic fate of CYX in animal liver microsomes, and to find out its related metabolites.…”