Comprehensive characterization of the pharmacokinetics, tissue distribution, and metabolism of Bufei Formula in rats

Abstract

Bufei Formula (BF), consisting of nine traditional Chinese medicinal herbs, is clinically applied to tonify qi, nourish the lung, relieve cough, and alleviate asthma. However, the chemical complexity of BF has hindered a clear understanding of its pharmacodynamic material basis and underlying in vivo mechanisms. This study aims to systematically elucidate the pharmacokinetics, tissue distribution, and metabolic profiles of BF in rats, thereby laying the groundwork for understanding its pharmacodynamic material basis. First, ultra-performance liquid chromatography (UPLC) was used to identify 18 major active constituents of BF. Subsequently, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to identify prototype compounds and metabolites in rat plasma, urine, feces, and tissues following oral administration of BF. In addition, a validated UPLC-MS/MS method was established for quantifying 14 active constituents. In total, 63 constituents were identified in vivo, including 17 prototype compounds and 46 metabolites. Among them, eight compounds showed the mean time to maximum plasma concentration (T_max) of 0.112–0.987 h, maximum plasma concentrations (C_max) of 4.995–213.333 μg/L, and the area under the plasma concentration–time curve (AUC) of 7.557–692.082 μg·h/L. Tissue distribution analysis revealed that the 14 quantified compounds were widely distributed in multiple organs, with predominant accumulation in the lung and colon, suggesting them as potential target organs. These findings provide a valuable reference for the clinical application of BF and evidence for elucidating its pharmacodynamic material basis.