Browse > Article
http://dx.doi.org/10.1016/j.jgr.2017.11.002

Differentiation and identification of ginsenoside structural isomers by two-dimensional mass spectrometry combined with statistical analysis  

Xiu, Yang (Jilin Ginseng Academy, Changchun University of Chinese Medicine)
Ma, Li (Institute of Mass Spectrometer and Atmospheric Environment, Jinan University)
Zhao, Huanxi (Jilin Ginseng Academy, Changchun University of Chinese Medicine)
Sun, Xiuli (Jilin Ginseng Academy, Changchun University of Chinese Medicine)
Li, Xue (Jilin Ginseng Academy, Changchun University of Chinese Medicine)
Liu, Shuying (Jilin Ginseng Academy, Changchun University of Chinese Medicine)
Publication Information
Journal of Ginseng Research / v.43, no.3, 2019 , pp. 368-376 More about this Journal
Abstract
Background: In the current phytochemical research on ginseng, the differentiation and structural identification of ginsenosides isomers remain challenging. In this paper, a two-dimensional mass spectrometry (2D-MS) method was developed and combined with statistical analysis for the direct differentiation, identification, and relative quantification of protopanaxadiol (PPD)-type ginsenoside isomers. Methods: Collision-induced dissociation was performed at successive collision energy values to produce distinct profiles of the intensity fraction (IF) and ratio of intensity (RI) of the fragment ions. To amplify the differences in tandem mass spectra between isomers, IF and RI were plotted against collision energy. The resulting data distributions were then used to obtain the parameters of the fitted curves, which were used to evaluate the statistical significance of the differences between these distributions via the unpaired t test. Results: A triplet and two pairs of PPD-type ginsenoside isomers were differentiated and identified by their distinct IF and RI distributions. In addition, the fragmentation preference of PPD-type ginsenosides was determined on the basis of the activation energy. The developed 2D-MS method was also extended to quantitatively determine the molar composition of ginsenoside isomers in mixtures of biotransformation products. Conclusion: In comparison with conventional mass spectrometry methods, 2D-MS provides more direct insights into the subtle structural differences between isomers and can be used as an alternative approach for the differentiation of isomeric ginsenosides and natural products.
Keywords
Differentiation; Ginsenoside isomers; Relative quantification; Two-dimensional mass spectrometry;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Seger C, Sturm S, Stuppner H. Mass spectrometry and NMR spectroscopy: modern high-end detectors for high resolution separation techniques - state of the art in natural product HPLC-MS, HPLC-NMR, and CE-MS hyphenations. Nat Prod Rep 2013;30:970-87.   DOI
2 Mcluckey SA, Wells JM. Mass analysis at the advent of the 21st century. Chem Rev 2001;101:571-606.   DOI
3 Fang TT, Bendiak B. The stereochemical dependence of unimolecular dissociation of monosaccharide-glycolaldehyde anions in the gas phase: A basis for assignment of the stereochemistry and anomeric configuration of monosaccharides in oligosaccharides by Mass Spectrometry via a key discriminatory product ion of disaccharide fragmentation, m/z 221. J Am Chem Soc 2007;129:9721-36.   DOI
4 Benassi M, Corilo YE, Uria D, Augusti R, Eberlin MN. Recognition and resolution of isomeric alkyl anilines by mass spectrometry. J Am Soc Mass Spectrom 2009;20:269-77.   DOI
5 Jiang K, Bian G, Pan Y, Lai G. Recognizing ortho-, meta- or para-positional isomers of S-methyl methoxylphenylmethylenehydrazine dithiocarboxylates by $ESI-MS^{2}$: The positional effect of the methoxyl substituent. Int J Mass Spectrom 2011;299:13-9.   DOI
6 Yang H, Shi L, Yao W, Wang Y, Huang L, Wan D, Liu S. Differentiation of disaccharide isomers by Temperature-Dependent In-Source Decay (TDISD) and DART-Q-TOF MS/MS. J Am Soc Mass Spectrom 2015;26:1599-605.   DOI
7 Song F, Liu Z, Liu S, Cai Z. Differentiation and identification of ginsenoside isomers by electrospray ionization tandem mass spectrometry. Anal Chim Acta 2005;531:69-77.   DOI
8 Ablajan K. A study of characteristic fragmentation of isoflavonoids by using negative ion $ESI-MS^{n}$. J Mass Spectrom 2011;46:77-84.   DOI
9 Han X, Gross RW. Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes. Expert Rev Proteomic 2005;2:253-64.   DOI
10 Liu D, Pan F, Liu J, Wang Y, Zhang T, Wang E, Liu J. Individual and combined antioxidant effects of ginsenoside $F_{2}$ and cyanidin-3-O-glucoside in Human Embryonic Kidney 293 cells. RSC Adv 2016;6:81092-100.   DOI
11 Lai CJS, Tan T, Zeng SL, Xu LR, Qi LW, Liu EH, Li P. An enzymatic protocol for absolute quantification of analogues: application to specific protopanoxadioltype ginsenosides. Green Chem 2015;17:2580-6.   DOI
12 Wang W, Zhao ZJ, Rayburn ER, Hill DL, Wang H, Zhang R. In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng. Cancer Chemoth Pharm 2007;59:589-601.   DOI
13 Domon B, Costello CE. A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj J 1988;5:397-409.   DOI
14 Cole RB. Electrospray and MALDI mass spectrometry. New Jersey: John Wiley & Sons; 2010.
15 Ho R. Handbook of Univariate and Multivariate Data Analysis and Interpretation with SPSS. Chapman & Hall/CRC; 2006.
16 Xiu Y, Zhao H, Gao Y, Liu W, Liu S. Chemical transformation of ginsenoside Re by a heteropoly acid investigated using $HPLC-MS^{n}/HRMS$. New J Chem 2016;40:9073-80.   DOI
17 Chan TWD, But PPH, Cheng SW, Kwok IMY, Lau FW, Xu HX. Differentiation and authentication of Panax ginseng, Panax quinquefolius, and ginseng products by using HPLC/MS. Anal Chem 2000;72:1281-7.   DOI
18 Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res 2009;55:1-99.   DOI
19 Oh J, Kim JS. Compound K derived from ginseng: neuroprotection and cognitive improvement. Food Funct 2016;7:4506-15.   DOI
20 Chen F, Zheng SL, Hu JN, Sun Y, He YM, Peng H, Zhang B, McClements DJ, Deng ZY. Octyl ester of ginsenoside $Rh_{2}$ induces apoptosis and G1 cell cycle arrest in human HepG2 cells by activating the extrinsic apoptotic pathway and modulating the Akt/p38 MAPK signaling pathway. J Agric Food Chem 2016;64:7520-9.   DOI
21 Li W, Gu C, Zhang H, Awang DVC, Fitzloff JF, Fong HH, van Breemen RB. Use of high-performance liquid chromatography-tandem mass spectrometry to distinguish Panax ginseng C. A. Meyer (Asian ginseng) and Panax quinquefolius L. (north American ginseng). Anal Chem 2000;72:5417-22.   DOI
22 Gross JH. Mass Spectrometry. 2nd ed. Berlin Heidelberg: Springer; 2011.
23 Yang H, Shi L, Zhuang X, Su R, Wan D, Song F, Li J, Liu S. Identification of structurally closely related monosaccharide and disaccharide isomers by PMP labeling in conjunction with IM-MS/MS. Sci Rep 2016;6:28079.   DOI
24 O'Hair RA. The 3D quadrupole ion trap mass spectrometer as a complete chemical laboratory for fundamental gas-phase studies of metal mediated chemistry. Chem Commun 2006;14:1469-81.   DOI
25 Baek SH, Bae ON, Park JH. Recent methodology in ginseng analysis. J Ginseng Res 2012;36:119-34.   DOI
26 Wong AST, Che CM, Leung KW. Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview. Nat Prod Rep 2015;32:256-72.   DOI
27 State Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China. Beijing: China Medical Science and Technology Press; 2010.
28 Liu ZQ. Chemical insights into ginseng as a resource for natural antioxidants. Chem Rev 2012;112:3329-55.   DOI
29 Ganesan P, Ko HM, Kim IS, Choi DK. Recent trends of nano bioactive compounds from ginseng for its possible preventive role in chronic disease models. RSC Adv 2015;5:98634-42.   DOI
30 Li KK, Gong XJ. A review on the medicinal potential of Panax ginseng saponins in diabetes mellitus. RSC Adv 2015;5:47353-66.   DOI
31 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology - In search of a pharmacophore. Biochem Pharmacol 1999;58:1685-93.   DOI
32 Kanie O, Shioiri Y, Ogata K, Uchida W, Daikoku S, Suzuki K, Nakamura S, Ito Y. Diastereomeric resolution directed towards chirality determination focussing on gas-phase energetics of coordinated sodium dissociation. Sci Rep 2016;6:24005.   DOI
33 Yang K, Zhao Z, Gross RW, Han X. Identification and quantitation of unsaturated fatty acid isomers by electrospray ionization tandem mass spectrometry: a shotgun lipidomics approach. Anal Chem 2011;83:4243-50.   DOI
34 Yu Q, Yu B, Yang H, Li X, Liu S. Silver (I)-assisted enantiomeric analysis of ginsenosides using electrospray ionization tandem mass spectrometry. J Mass Spectrom 2012;47:1313-21.   DOI
35 W'ang Y, Choi HK, Brinckmann JA, Jiang X, Huang L. Chemical analysis of Panax quinquefolius (North American ginseng): a review. J Chromatogr A 2015;1426:1-15.   DOI
36 Wong YLE, Chen X, Li W, Wang Z, Hung YLW, Wu R, Chan TWD. Differentiation of isomeric ginsenosides by using electron-induced dissociation mass spectrometry. Anal Chem 2016;88:5590-4.   DOI
37 Cancilla MT, Wong AW, Voss LR, Lebrilla CB. Fragmentation reactions in the mass spectrometry analysis of neutral oligosaccharides. Anal Chem 1999;71:3206-18.   DOI
38 Daikoku S, Ako T, Kato R, Ohtsuka I, Kanie O. Discrimination of 16 structural isomers of fucosyl galactoside based on energy-resolved mass spectrometry. J Am Soc Mass Spectrom 2007;18:1873-9.   DOI
39 Yu X, Huang Y, Lin C, Costello CE. Energy-dependent electron activated dissociation of metal-adducted permethylated oligosaccharides. Anal Chem 2012;84:7487-94.   DOI
40 Kenttamaa HI, Cooks RG. Tautomer characterization by energy resolved mass spectrometry. Dimethyl phosphite and dimethyl phosphonate ions. J Am Chem Soc 1985;107:1881-6.   DOI
41 Gao J, Shi J, Lu X, Sun C, Pan Y. Differentiation of common diastereoisomeric ursane-type triterpenoids by high-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2011;25:1349-55.   DOI