GC-Orbitrap-HRMS coupled with microdialysis: A novel approach for non-targeted analysis of transdermal constituents...

Acupoint sticking therapy (AST) is a traditional Chinese transdermal treatment widely used for chronic conditions such as asthma and dyspepsia. Despite its clinical efficacy, the material basis of AST, particularly the penetration dynamics of its active transdermal components, remains unclear, hindering further investigation into its therapeutic mechanisms. This study developed an integrated platform combining in vivo microdialysis with GC-Orbitrap-HRMS to characterize transdermal components and penetration profiles of AST, using the Jianpi Patch (JPT) as a model due to its proven efficacy in pediatric functional dyspepsia. Firstly, 204 volatile compounds in JPT were identified, including terpenoids, hydrocarbons, esters, ketones and alcohols. Furthermore, through real-time microdialysis at the Shenque (CV8) acupoint in rats, 66 compounds were identified as transdermal constituents by GC-Orbitrap-HRMS. Based on their transdermal profiles, these penetrating components were categorized into three distinct patterns: rapid penetration (peak within 1-2 h), delayed peak (gradual increase, maximum at 3-4 h), and sustained release (progressive rise, peak at 5-6 h). This work established a minimally invasive platform for screening the material basis of transdermal herbal formulations and provided new insights into the permeation behavior of AST.