A metabolomics-based strategy for the quality control of traditional chinese medicine: shengmai injection as a case study

Abstract

Quality control of traditional Chinese medicines (TCMs) used clinically is becoming a challenge and has limited the development of TCM due to the high variability in concentration levels of active ingredients and markers as well as the lack of well-established criteria. Using Shengmai injection, which is a well-established TCM, as an example, we developed an integrated profiling approach that simultaneously captures the entire spectrum of ingredients and quantitatively determines the levels of seven key ingredients in the TCM product. A multivariate statistical model was constructed to establish a "seven-marker-" based quality standard that qualified the majority of samples in this study. This newly developed strategy showed that a panel of key ingredients or markers in the TCM product were relatively consistent within a statistically acceptable range. Therefore, this metabolomics-based approach will complement the current quality control standard using the concentration of several key ingredients or their total content and help improve the consistency and clinic efficacy of TCM products.

Figure 1

Schematic diagram of the strategy used for the quality control of traditional Chinese medicine (TCM). (1) LC-TOF-MS analysis of TCM; (2) Pretreatment data obtained from the LC-TOF-MS analysis; (3) Data export using software; (4) Exported.xml data files are analyzed using the open source XCMS package to pick, align, and quantify features; (5) The resulting 3D matrix contains arbitrarily assigned peak index, retention time, and abundance value (.xls file); (6) The  .xls data files are then exported to SIMCA-P software 12.0 (Umetrics, Umeå, Sweden) for multivariate statistical analysis; (7) A quality control standard is then established; (8) The established standard is used for quality control of TCM.

Figure 2

Extracted ion chromatograms of eight ginsenosides, including Rg1, Rb1, Re, Rb2, Rg2, Rf, Rd, and Rc.

Figure 3

Total ion current (TIC) chromatograms of four Shengmai injection samples.

Figure 4

PCA sores plot of (a) metabolic profile of 22 Shengmai injection samples using all of the data and (b) metabolic profile of 22 Shengmai injection samples using the ginsenoside quantitative data.

Figure 5

PCA scores plot of the ginsenoside metabolite profile of 22 Shengmai injection samples obtained from four different manufacturers. Blue dot: sample A; green dot: sample B; black dot: sample C; red dot: sample D.