Abstract
In an LC-MS investigation of drug metabolic samples from the traditional Chinese medicine Chaihu, the baseline was established via MS selectivity-based chromatogram baseline-shift elimination and exogenous metabolite signals were obtained with MS-based orthogonal projection. Their respective influences on the metabolic chromato-graphic profiles, metabonomics model and evaluation of drug toxicity were investigated. The baseline shift enhanced the difference between the metabolic profiles of the control and Chaihu groups, and the corresponding correlation coefficient decreased from 70.38% to 62.69%. The exogenous metabolite signal led to a biased expression of the evaluated toxicity, and the enhanced expression resulted in an average Mahalanobis distance of approximately 9.4%. Based on established metabonomics models, the results show that Chaihu induces liver toxicity at a lower dose of 25 g/kg, twice a day. At this dose, Chaihu elicits a process of self-repair for its liver toxicity. The signal intensities of exogenous metabolites from Chaihu changed with the administration time, but only the signal intensities of large molecule metabolites(m/z 500―850) from Chaihu had a positive correlation with its toxicity. These results suggest that liver toxicity from low doses of Chaihu was probably caused by the larger molecule components and not by its active components, saikosaponin and flavonoid glycoside.
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Supported by the National Natural Science Foundation of China(No.81001686) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.
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Zeng, Q., Feng, J., Lü, T. et al. Influence of chromatogram baseline shifts and exogenous metabolite signals on metabolic profiles of traditional Chinese medicine Chaihu and its liver toxicity metabonomics. Chem. Res. Chin. Univ. 33, 17–23 (2017). https://doi.org/10.1007/s40242-017-6302-z
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DOI: https://doi.org/10.1007/s40242-017-6302-z