An ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/Q-TOFMS) based chemical profiling approach to evaluate chemical constitution between mixed decoction and co-decoction of Radix aconiti-Fritillaria combination of the Eighteen Incompatible Medications (Shi Ba Fan) was proposed. Two different kinds of decoctions, namely Radix aconiti-Fritillaria co- decoction: water extract of mixed two herbs, and Radix aconiti-Fritillaria mixed decoction: mixed water extract of each individual herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC/Q-TOFMS analysis, the datasets were processed with MassLynx 4.1 to holistically compare the difference between these two kinds of decoction samples. The most changed components during decocting were analyzed. Using the proposed approach, global chemical difference was found between co-decoction and mixed decoction, hypaconitine was identified as the most changed toxic components (changed most significantly) during co-decocting. Result shows the hydrolysis of hypaconitine were inhibited after co-decoction of Radix aconiti-Fritillaria, and other major diester diterpenoid alkaloids were hydrolysis most completely. For the co-decoction of Radix aconite combined with Bulbus fritillariae cirrhosae, the content of hypaconitine and deoxyaconitine is more than that of Radix aconiti-Bulbus fritillariae thunbergii.

Key words: eighteen incompatible medications, UPLC, Q-TOFMS, LC-MS, Aconitum, Fritillaria