Integrated LC‐MS and Network Pharmacology Reveal Metabolic Profile and Quantitative Analysis of Active Components in Coptidis Rhizoma–Aucklandiae Radix Herb Pair Between Healthy and Diarrheal Mice

ABSTRACT Introduction Antibiotic‐associated diarrhea (AAD) is a common side effect after the use of antibiotics, characterized by symptoms like diarrhea and abdominal pain. However, the active components and in vivo metabolism of the Coptidis Rhizoma–Aucklandiae Radix herb pair (CR‐AR) in the treatment of AAD remain unclear. Objective This study aimed to (1) investigate the prototype components, metabolites, and potential metabolic pathways of CR‐AR in AAD mice and (2) compare the concentration of six active components between healthy and AAD mice. Materials and Methods AAD model mice received oral administration of the CR‐AR extract. UPLC‐Q‐Exactive‐Orbitrap‐HRMS was used to analyze the prototype components and metabolites in serum, feces, and intestines of AAD mice. A prototype components–targets–pathways–AAD network was developed using network pharmacology to identify active components and effective targets of CR‐AR in treating AAD, based on prototypes detected in serum, fecal, and intestinal samples. Additionally, a comparative analysis of the concentration of six active components was conducted between healthy and AAD mice using UPLC‐QqQ‐MS. Results A total of 45 components were identified in the extract of CR‐AR. Among them, 16 prototype compounds and 47 metabolites were identified, and potential metabolic pathways (including hydroxylation, demethylation, reduction, hydrolysis, hydrogenation, and glucuronidation) were proposed. Based on the 16 prototype components, six potentially active components (berberine, jatrorrhizine, palmatine, columbamine, epiberberine, and dehydrocostus lactone) were screened from the prototype components–targets–pathways–AAD disease network. Targeted quantitative analysis showed that alkaloid‐based active components were significantly more concentrated in the intestines of AAD mice than in healthy mice after 6 h ( p < 0.05).