In Vivo Metabolite Profiling of <i>Radix scutellariae–Licorice</i> Herb Pair Compared With Single Herbs by Ultra‐High‐Performance Liquid Chromatography‐Quadrupole Time‐of‐Flight‐Tandem Mass Spectrometry

ABSTRACT Radix scutellariae and Licorice are representative herbs in traditional Chinese medicine, widely employed for the management of inflammatory disorders owing to their well‐recognized anti‐infective and anti‐inflammatory properties. In clinical practice, they are often prescribed in combination; however, their precise mechanisms of action and metabolic interactions remain insufficiently elucidated. In the present study, an ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐tandem mass spectrometry approach was utilized to comprehensively profile the in vivo metabolites of Radix scutellariae , Licorice , and their co‐administration in rats. Biological matrices, including bile, urine, and feces, were examined to identify biotransformation pathways and to compare metabolic signatures between single‐herb and combined administration. A total of 87 metabolites were characterized, encompassing a wide array of transformations such as oxidation, hydrogenation, sulfation, and methylation. Notably, the herb pair facilitated distinct metabolic conversions and reshaped the overall metabolite spectrum relative to individual herbs. These results provide mechanistic insights into the metabolic basis of this classical herb pair and suggest potential directions for further pharmacological research and clinical application.