Potential of hyphenated ultra-high performance liquid chromatography-scheduled multiple reaction monitoring algorithm for large-scale quantitative analysis of traditional Chinese medicines

Abstract

It is a great challenge to perform quality control for traditional Chinese medicines (TCMs) that contain a great number of constituents by holistically monitoring hydrophilic and hydrophobic substances. Theoretically, the relatively low scan rate of triple quadrupole (QqQ) equipment makes it quite difficult to meet the demands of reliable quantitation of the narrow peaks generated from ultra-high performance liquid chromatography (UHPLC). Scheduled multiple reaction monitoring (sMRM) algorithm offers the potential to simultaneously monitor numerous analytes without compromising data quality, in particular for co-eluting compounds, by automatically altering the dwell time to maintain the desired cycle time on a QqQ analytical platform. In the current study, UHPLC and sMRM were hyphenated to develop a practical and robust quantitative method for as many as 133 TCM-derived components, including polar and apolar compounds. Efficient separation was achieved on a core–shell-type column (Capcell core ADME column) with adamantylethyl functional groups to generate appropriate surface polarity along with hydrophobicity in comparison with RP-C₁₈ and HILIC columns. To verify the applicability of the developed UHPLC-sMRM method, a formula was simulated by mixing eight TCM raw materials that related to those 133 analytes. Moreover, enhanced product ion scans were triggered by sMRM to acquire MS² spectra to enhance the confidence of peak assignment. Method validation results suggested the developed method to be accurate, precise, and reproducible. In comparison with conventional MRM, sMRM was proved to be advantageous in terms of sensitivity and precision, as well as the dependent MS² spectral quality. Above all, our current study indicated that the integration of UHPLC and sMRM provides the potential to globally and simultaneously quantify the components in TCMs.