Synergistic profiling of Angelicae sinensis Radix-Cinnamomi Cortex: Comparative pharmacokinetics, tissue distribution, excretion, and in sillico metabolism prediction.

Angelicae sinensis Radix-Cinnamomi Cortex herb pair (ACHP) is extensively utilized in traditional Chinese medicine (TCM) formulas to dispel cold, tonify kidney yang and relieve pain. However, the in vivo dynamics of its bioactive constituents during co-administration remain unclear. Here, the absorption, distribution, and excretion profiles of four representative components, senkyunolide I (1), ferulic acid (2), cinnamic alcohol (3) and cinnamic acid (4), were compared in rats following the oral administration of the individual herbs versus the ACHP extract. Together with in silico metabolism prediction, this study aimed to provide insights into in vivo herb-herb interactions and the potential therapeutic material basis of ACHP. A validated UHPLC-QQQ-MS/MS method was developed to quantify these analytes across multiple biological matrices. Key pharmacokinetic parameters, including AUC(0-t), AUC(0-∞), t1/2 and CLz/F, differed significantly (p < 0.05, p < 0.01) in the ACHP group compared to the single-herb groups. All compounds exhibited rapid tissue distribution and low biliary recovery. Excretion studies revealed that 1-3 were primarily eliminated via feces, whereas 4 was mainly excreted through urine. For metabolite prediction, GLORYx and BioTransformer 3.0 were employed to characterize the potential metabolic profile. Taken together, these findings demonstrate that ASR-CC compatibility significantly modulates the in vivo disposition of the primary bioactive components, providing pharmacokinetic evidence for the synergistic efficacy of ACHP.