A multi-component quality control strategy for Sanpian Decoction using MESI-mini-MS/MS: rapid on-site evaluation of complex traditional Chinese medicine formulas

Traditional Chinese medicine (TCM) formulas exhibit remarkable clinical efficacy owing to their multi-component and multi-target characteristics, yet their inherent chemical complexity poses significant challenges for quality control (QC). This study, using the classical famous formula Sanpian Decoction as an example, developed a rapid multi-component quality control method for TCM formulations based on membrane electrospray ionization coupled with miniature mass spectrometry (MESI-mini-MS). High-resolution UPLC-Q-TOF-MS/MS and GC-MS analyses were first employed to comprehensively characterize the chemical profile. Next, 12 representative active components from different chemical classes were selected as qualitative and quantitative markers, considering their pharmacological significance and proportional representation in the formula. Then, a MESI-mini-MS/MS qualitative and quantitative method was established based on the reference standards of the 12 representative active compounds. In this process, the multiple reaction monitoring (MRM) strategy was employed. The analytical methodology, including the validation of its precision, accuracy, recovery, and stability, was thoroughly verified. Finally, the established method was applied to the direct analysis of 15 batches of Sanpian Decoction benchmark samples. The results demonstrated that it could rapidly and reliably quantify the 12 marker compounds, enabling fast quality control. Classical UPLC fingerprinting was used to validate the rapid quality control results, showing consistent conclusions between the two methods. This highlights the potential of MESI-mini-MS/MS as a portable, efficient, and robust tool for on-site quality control of complex TCM formulations, providing a practical solution to support the modernization of TCM production.