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Objective To establish an effective approach for rapid and comprehensive analysis on the absorbed and metabolic components in rats after ig administration of Yuanhu Zhitong Dropping Pill(YHZT). Methods Based on the combination of UPLC-Q-TOF/MS and multivariate statistical analysis, the absorbed prototype constituents and their metabolites in rat plasma were rapidly analyzed and identified, and the components absorbed into brain were further identified by comparing the extracted ion chromatograms(EICs) of control and brain tissue samples of dosed rats. Results A total of 38 YHZT-related xenobiotic compounds were detected and identified as the potential bioactive constituents in rat plasma, including 24 absorbed prototype constituents and 14 metabolites. In particular, of all prototype constituents, 14 were also detected in rat brain tissue, indicating that they could penetrate the blood-brain barrier and enter into brain. Conclusion An effective method is established and applied to analyze the potential bioactive constituents in YHZT, which provides a pathway to further investigate the pharmacological pattern and mechanism of YHZT.