A rapid and comprehensive quality assessing method of Yin-Qiao-Jie-Du tablets using UHPLC-QTOF-MS in combination with multivariate statistical analysis

Abstract

Yin-Qiao-Jie-Du (YQJD) tablet is a well-known non-prescription Chinese patent drug widely used for the prevention and treatment of diseases in China. However, documented studies for assessing and controlling the quality of YQJD tablet are limited. In this article, a rapid and comprehensive method for the quality assessment and control of YQJD tablets was developed, via qualitative and quantitative analysis of the major active ingredients of YQJD tablets by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. The samples of YQJD tablets were triturated and then extracted with methanol, and the extracts were analyzed by UHPLC-QTOF-MS. A good separation was achieved within 30min by using an Agilent RRHD SB-C18 (150mm×2.1mm I.D., 1.8μm) column with a gradient elution of water (0.5% formic acid) and acetonitrile. Forty-one major chromatographic peaks were obtained, and 31 of them were identified according to the obtained data from the measurements of accurate mass, isotopic composition, and collision-induced dissociation. Among them, 21 were confirmed by the comparison of retention times, MS, and MS/MS information with those of their references. Quantitative analysis was performed based on the peak areas of extracted ion chromatograms of the exact pseudo-molecular ions (with a 0.01Da window), and the result of method validation demonstrated that the proposed method possessed desirable specificity, linearity, precision, and accuracy. Subsequently, the method was utilized to analyze the major constituents in YQJD tablets of 18 batches produced by different manufacturers. The obtained contents of the 21 confirmed ingredients were applied for orthogonal partial-least squares to latent structures discriminant analysis (OPLS-DA). An assessment of the quality consistency and stability as well as tracing the origins of the investigated YQJD tablets were successfully achieved by OPLS-DA. All of these results demonstrated that the UHPLC-QTOF-MS method developed in this study was a rapid and desirable approach for differentiating the origin, discriminating the authenticity, and assessing and controlling the quality of YQJD tablets.