Metabonomics of liver toxicity from Traditional Chinese Medicine Huang-Yao-Zi studied by mass spectrum-based orthogonal projection method

• Exogenous metabolites affected the metabonomics models and drug toxicity evaluation.
• The range of fragment ions from exogenous metabolites moved to the high m/z range.
• Urine samples data was generated from rats by UPLC/ESI-MS.

Based on mass spectrum-based orthogonal projection (MSOP) method, the exogenous metabolite signal from Huang-Yao-Zi (HYZ) was obtained, and its effect on metabonomics model and toxicity evaluation was studied. The exogenous metabolite signal increased with prolonged administration time, showing an accumulative effect. Meanwhile, the exogenous metabolites with low molecular weight decreased but the ones with high molecular weight increased and the concentration of exogenous metabolites with high molecular weight rose notably, suggesting that the metabolic way of HYZ has changed. Metabonomics model revealed that the distance between the control and HYZ groups decreased after eliminating the exogenous metabolite signals. In addition, the potential biomarkers were preliminary studied. These results indicated that exogenous metabolite signal led to a stronger expression of the evaluated liver toxicity from HYZ and MSOP method would be of great significance for toxicity evaluation in Traditional Chinese Medicine.