UPLC-QTOF/MS-Based Metabolomics Applied for the Quality Evaluation of Four Processed _Panax ginseng_ Products  
[PERSON]  
1 Department of Herbal Crop Research, National Institute of Herbal Science, RDA, Eunseong 27709, Korea; [EMAIL_ADDRESS] (J.W.L.); [EMAIL_ADDRESS] (S.-H.J.); [EMAIL_ADDRESS] (B-R.C.); [EMAIL_ADDRESS] (D.J.C.); [EMAIL_ADDRESS] (G-S.K.)  
2 Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin 17104, Korea; [EMAIL_ADDRESS] (Y-G.L.); [EMAIL_ADDRESS] (H.-G.K.); [EMAIL_ADDRESS] (N.-I.B.)  
3 Institute of JinAn Red Ginseng, JinAn 55442, Korea; [EMAIL_ADDRESS]  
4 Department of Horticultural Biotechnology, Kyung Hee University, Yongin 17104, Korea; [EMAIL_ADDRESS]  
5 Correspondence: [EMAIL_ADDRESS]; Tel.: +82-43-871-5784; Fax: +82-43-871-5759  
the major bioactive components of these ginseng products [9; 10]. In particular, the qualitative and quantitative contents of ginseng differ depending on the distinct methods used to process raw ginseng [3; 11; 12]. Dehydration and steaming treatments can induce chemical changes in ginseng, which are converted to new bioactive compounds that are not present in raw ginseng [10; 13]. For example, WG contains malonyl-ginsenosides (MGR), where a malonyl residue is linked to the glucose of the molecule, while the thermally unstable malonyl residue can be hydrolyzed by a steaming treatment to manufacture RG or BG [14]. Furthermore, BG contains specific ginsenosides, and exhibits more potent pharmacological effects than WG and RG [15]. A variety of ginsenosides have different bioactivities and clinical applications, such as anti-tumor, anti-diabetes, anti-oxidatives, etc. [16; 17; 18]. Hence, it is critical to assess the levels of ginsenosides for the quality control and effective usage of processed ginseng products.  
In the last few decades, more than 150 different ginsenosides have been isolated and identified by nuclear magnetic resonance (NMR) spectroscopy [19; 20]. Furthermore, many analytical methods such as high performance liquid chromatography (HPLC) coupled to UV detector [21; 22], evaporative light scattering detector (ELSD) [7; 23], or mass spectrometry (MS) [24; 25] have been used to analyze various ginsenosides from the _P. ginseng_ samples. In particular, ultra-performance LC coupled with quadrupole time of flight/MS (UPLC-QTOF/MS) has emerged as a fast and sensitive tool for the comprehensive profiling of ginsenosides [26; 27]. A full mass scan mode using QTOF/MS is effective to explore various ginsenosides, as well as many other metabolites in complex mixtures [28]. Recently, for the holistic quality evaluation of processed ginseng products, metabolomics approaches based on UPLC-QTOF/MS have been used to profile various metabolites including ginsenosides [29; 30]. Multivariate analyses are used, such as principal component analysis (PCA), which indicates whether any differences exist among samples, and orthogonal partial least squared discrimination analysis (OPLS-DA), which identifies which compounds have been altered for the quality evaluation of commercial WG and RG [30]. A well-constructed metabolomics approach combined with multivariate analyses will be useful for the quality evaluation of other processed ginseng products, such as TG and BG. Until now, many researchers have reported the analysis of WG and RG, whereas there are few studies on the metabolic components of TG and BG.  
In this study, we applied the metabolomics approach based on UPLC-QTOF/MS to assess the metabolic compositions of WG, TG, RG, and BG. In the multivariate analyses, several ginsenosides were represented as major components to differentiate these four processed ginseng products. Furthermore, the qualitative and quantitative contents of ginsenosides were characterized for the quality evaluation of WG, TG, RG, and BG.