Development of a comprehensive method combining UHPLC-CAD fingerprint, multi-components quantitative analysis for quality evaluation of Zishen Yutai Pills: A step towards quality control of Chinese patent medicine.

Zishen Yutai Pills (ZYP) is a well-known Chinese patent medicine which has been used to prevent recurrent miscarriage and treat threatened abortion in China. In this study, a comprehensive strategy combining ultrahigh performance liquid chromatography coupled with charged aerosol detector (UHPLC-CAD) fingerprint and multi-components quantitative analysis was developed and validated for quality evaluation of ZYP. For fingerprint analysis, a total of 52 characteristic peaks were selected to evaluate the similarities of 16 batches of ZYP. In addition, combining the chemical fingerprint profile with an advanced hybrid LTQ-Orbitrap mass spectrometer, 281 compounds were identified or tentatively identified in ZYP based on chemical standards, accurate mass and fragmentation information. Moreover, 18 chemical markers were simultaneously determined within 13 min by ultra-performance liquid chromatography couple to tandem mass spectrometry (UPLC-MS/MS) with positive-negative conversion multiple reaction monitor (+/-MRM) technique. This method has been validated and exhibited satisfactory sensitivity, precision, reproducibility and accuracy. The validated quantitative method was successfully applied to the analysis of 16 batches of ZYP samples. The combination of UHPLC-CAD fingerprint and multi-components quantification has been proved to be an efficient and reliable strategy for quality control of ZYP and could be considered as a reference for quality evaluation of Chinese patent medicine.