Multi-responses extraction optimization based on response surface methodology combined with polarity switching HPLC-MS/MS for the simultaneous quantitation of 11 compounds in Cortex Fraxini: application to four species of Cortex Fraxini and its 3 confusable species.

Abstract A novel polarity switching high performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC–ESI-MS/MS) approach combining optimization of extraction condition by response surface methodology (RSM) was developed for the simultaneous quantitative analysis of 11 compounds in Cortex Fraxini, a commonly used traditional Chinese medicine. The ultrasonic extraction conditions of the 11 analytes including sample quantity, methanol concentration and extraction time were simultaneously optimized with a Box–Behnken design (BBD) and Derringer's desirability function. Multiple-reaction monitoring (MRM) scanning was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run of 16 min. Quantitative parameters of the proposed method with respect to limit of detection (LOD), limit of quantification (LOQ), linearity, precision, accuracy and stability were evaluated under optimum conditions, and the results indicated that the method was sensitive, specific and reliable. The developed method was successfully applied to determine the investigated compounds in four species of Cortex Fraxini and three kinds of its confusable species, and significant differences were found between the official and confusable species.