Metabolic profiling of Danzhi Jiangtang capsule in rat plasma, urine and feces by UPLC-Q-TOF/MSE combined with a multiple-point screening mass defect filtering strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi Jiangtang capsule (DJC) is a traditional Chinese medicine prescription to treat type 2 diabetes mellitus and its complications. However, an in-depth understanding of DJC metabolism in vivo is lacking.

AIM OF THE STUDY: In this study, an analytical strategy combining ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with multiple-point screening mass defect filtering (MDF) to characterize DJC's absorbed prototype compounds and metabolic profiles in rat plasma, urine, and feces.

MATERIALS AND

METHODS

Firstly, a compound database of 137 identified compounds in DJC was established based on our previous study, and the biological samples were comprehensively analysed using UPLC-Q-TOF/MS, with prototype compounds identification completed by direct identification method. Then, R language combined with MZmine was used for data preprocessing to construct ion information lists and extract valid data. Concurrently, related metabolites and possible metabolic pathways were predicted. Subsequently, the identification of the DJC-related metabolites were completed by multi-point screening MDF and direct identification method.

RESULTS

As a result, 98 exogenous compounds in plasma (16 prototypes + 82 metabolites), 120 in urine (20 prototypes + 100 metabolites), and 86 in feces (12 prototypes + 74 metabolites) were identified. The metabolic transformations predominantly involved phase I metabolism (oxidation, reduction, hydration, deglycosylation, demethylation, decarboxylation and dehydration) and phase II metabolism (glucuronidation, sulfation, acetylation and methylation).

CONCLUSIONS

This study systematically elucidated the biotransformation pathways of DJC in rat biological samples, identified the metabolic substance profiles following oral administration, and provided critical data support for the precise characterization of its pharmacologically active compounds.