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Simultaneous quantification of endogenous and exogenous plasma glucose by isotope dilution LC-MS/MS with indirect MRM of the derivative tag

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Abstract

Quantification of endogenous and exogenous plasma glucose can help more comprehensively evaluate the glucose metabolic status. A ratio-based approach using isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was developed to simultaneously quantify endo-/exogenous plasma glucose. Using diluted D-[13C6] glucose as tracer of exogenous glucose, 12C6/13C6 glucoses were first derivatized and then data were acquired in MRM mode. The metabolism of exogenous glucose can be tracked and the concentration ratio of endo/exo-genous glucose can be measured by calculating the endo-/exo-genous glucose concentrations from peak area ratio of specific daughter ions. Joint application of selective derivatization and MRM analysis not only improves the sensitivity but also minimizes the interference from the background of plasma, which warrants the accuracy and reproducibility. Good agreement between the theoretical and calculated concentration ratios was obtained with a linear correlation coefficient (R) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which covers the healthy and diabetic physiological scenarios. Satisfactory reproducibility was obtained by evaluation of the intra- and inter-day precisions with relative standard deviations (RSDs) less than 5.16%, and relative recoveries of 85.96 to 95.92% were obtained at low, medium, and high concentration, respectively. The method was successfully applied to simultaneous determination of the endo-/exogenous glucose concentration in plasma of non-diabetic and type II diabetic cynomolgus monkeys.

Graphical Abstract

The scheme of the proposed ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the derivative tag for simultaneous quantification of endogenous and exogenous plasma glucose.

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References

  1. Ross SA, Gulve EA, Wang MH. Chemistry and biochemistry of type 2 diabetes. Chem Rev. 2004;104(3):1255–82. https://doi.org/10.1021/cr0204653.

    Article  CAS  Google Scholar 

  2. Zhu P, Sun WW, Zhang CL, Song ZY, Lin S. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease. Int J Cardiol. 2016;220:235–41. https://doi.org/10.1016/j.ijcard.2016.06.138.

    Article  Google Scholar 

  3. Balaji V, Balaji M, Anjalakshi C, Cynthia A, Arthi T, Seshiah V. Diagnosis of gestational diabetes mellitus in Asian-Indian women. Indian J Endocrinol Metab. 2011;15(3):187–90. https://doi.org/10.4103/2230-8210.83403.

    Article  CAS  Google Scholar 

  4. Ogawa Z, Kanashima M, Nishioka H. Improvement of the quantitative method for glucose determination using hexokinase and glucose 6-phosphate dehydrogenase. Clin Chem Lab Med. 2001;39(5):396–400. https://doi.org/10.1515/cclm.2001.063.

    Article  CAS  Google Scholar 

  5. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55(10):2688–97. https://doi.org/10.2337/db05-1404.

    Article  CAS  Google Scholar 

  6. Tripathy D, Almgren P, Tuomi T, Groop L. Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity. Diabetes Care. 2004;27(9):2204–10. https://doi.org/10.2337/diacare.27.9.2204.

    Article  CAS  Google Scholar 

  7. Defronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose-metabolism in noninsulin-dependent (type-II) diabetes-mellitus. J Clin Invest. 1985;76(1):149–55. https://doi.org/10.1172/jci111938.

    Article  CAS  Google Scholar 

  8. Antonopoulos A, Bonnet P, Botek E, Debrun JL, Hakim B, Herbreteau B, et al. Study of the attachment of Na+ on glucose and on some of its methylated derivatives. Rapid Commun Mass Spectrom. 2003;17(2):122–5. https://doi.org/10.1002/rcm.881.

    Article  CAS  Google Scholar 

  9. McIntosh TS, Davis HM, Matthews DE. A liquid chromatography-mass spectrometry method to measure stable isotopic tracer enrichments of glycerol and glucose in human serum. Anal Biochem. 2002;300(2):163–9. https://doi.org/10.1006/abio.2001.5455.

    Article  CAS  Google Scholar 

  10. Wan ECH, Yu JZ. Determination of sugar compounds in atmospheric aerosols by liquid chromatography combined with positive electrospray ionization mass spectrometry. J Chromatogr A. 2006;1107(1–2):175–81. https://doi.org/10.1016/j.chroma.2005.12.062.

    Article  CAS  Google Scholar 

  11. Rogatsky E, Jayatillake H, Goswami G, Tomuta V, Stein D. Sensitive LC MS quantitative analysis of carbohydrates by CS+ attachment. J Am Soc Mass Spectrom. 2005;16(11):1805–11. https://doi.org/10.1016/j.jasms.2005.07.017.

    Article  CAS  Google Scholar 

  12. Kato Y, Numajiri Y. Chloride attachment negative-ion mass spectra of sugars by combined liquid-chromatography and atmospheric-pressure chemical ionization mass spectrometry. J Chromatogr Biomed Appl. 1991;562(1–2):81–97. https://doi.org/10.1016/0378-4347(91)80567-v.

    Article  CAS  Google Scholar 

  13. Rogatsky E, Tomuta V, Stein DT. LC/MS quantitative study of glucose by iodine attachment. Anal Chim Acta. 2007;591(2):155–60. https://doi.org/10.1016/j.aca.2007.04.001.

    Article  CAS  Google Scholar 

  14. Rijke ED, Bouter N, Ruisch BJ, Haiber S, Konig T. Identification of N-gluconyl ethanolamine in wine by negative electrospray ionization with post-column chloride attachment and accurate mass determination on a triple-quadrupole mass spectrometer. J Chromatogr A. 2007;1156:296–303. https://doi.org/10.1016/j.chroma.2008.08.007.

    Article  Google Scholar 

  15. Wan ECH, Yu JZ. Analysis of sugars and sugar polyols in atmospheric aerosols by chloride attachment in liquid chromatography/negative ion electrospray mass spectrometry. Environ Sci Technol. 2007;41(7):2459–66. https://doi.org/10.1021/es062390g.

    Article  CAS  Google Scholar 

  16. Macasek F, Bruder P, Patakyova A, Buriova E. Atmospheric pressure electrospray ionization mass spectra of glucose and 2-fluorodeoxyglucose for quantitative analysis of 2-fluorodeoxyglucose by high-performance liquid chromatography. Eur J Mass Spectrom. 2003;9(2):129–37. https://doi.org/10.1255/ejms.529.

    Article  CAS  Google Scholar 

  17. Clapperton AT, Coward WA, Bluck LJC. Measurement of insulin sensitivity indices using 13C-glucose and gas chromatography/combustion/isotope ratio mass spectrometry. Rapid Commun Mass Spectrom. 2002;16(21):2009–14. https://doi.org/10.1002/rcm.815.

    Article  CAS  Google Scholar 

  18. Bluck LJC, Clapperton AT, Coward WA. 13C- and 2H-labelled glucose compared for minimal model estimates of glucose metabolism in man. Clin Sci. 2005;109(6):513–21. https://doi.org/10.1042/Cs20050155.

    Article  CAS  Google Scholar 

  19. Schierbeek H, Moerdijk-Poortvliet TCW, van den Akker CHP, te Braake FWJ, Boschker HTS, van Goudoever JB. Analysis of [U-13C6] glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry compared with two other mass spectrometry techniques. Rapid Commun Mass Spectrom. 2009;23(23):3824–30. https://doi.org/10.1002/rcm.4293.

    Article  CAS  Google Scholar 

  20. Gonzalez-Antuna A, Dominguez-Romero JC, Garcia-Reyes JF, Rodriguez-Gonzalez P, Centineo G, Alonso JIG, et al. Overcoming matrix effects in electrospray: quantitation of beta-agonists in complex matrices by isotope dilution liquid chromatography-mass spectrometry using singly 13C-labeled analogues. J Chromatogr A. 2013;1288:40–7. https://doi.org/10.1016/j.chroma.2013.02.074.

    Article  CAS  Google Scholar 

  21. Zhang TJ, Zhang CB, Zhao HJ, Zeng J, Zhang JT, Zhou WY, et al. Determination of serum glucose by isotope dilution liquid chromatography-tandem mass spectrometry: a candidate reference measurement procedure. Anal Bioanal Chem. 2016;408(26):7403–11. https://doi.org/10.1007/s00216-016-9817-0.

    Article  CAS  Google Scholar 

  22. Andersen KE, Bjergegaard C, Sorensen H. Analysis of reducing carbohydrates by reductive tryptamine derivatization prior to micellar electrokinetic capillary chromatography. J Agric Food Chem. 2003;51(25):7234–9. https://doi.org/10.1021/jf030329e.

    Article  CAS  Google Scholar 

  23. Guigo N, Mazeau K, Putaux JL, Heux L. Surface modification of cellulose microfibrils by periodate oxidation and subsequent reductive amination with benzylamine: a topochemical study. Cellulose. 2014;21(6):4119–33. https://doi.org/10.1007/s10570-014-0459-0.

    Article  CAS  Google Scholar 

  24. Hurtado-Sanchez MD, Espinosa-Mansilla A, Duran-Meras I. Influence of the presence of natural monosaccharides in the quantification of alpha-dicarbonyl compounds in high content sugar samples. A comparative study by ultra-high performance liquid chromatography-single quadrupole mass spectrometry using different derivatization reactions. J Chromatogr A. 2015;1422:117–27. https://doi.org/10.1016/j.chroma.2015.10.001.

    Article  CAS  Google Scholar 

  25. Gensberger-Reigl S, Huppert J, Pischetsrieder M. Quantification of reactive carbonyl compounds in icodextrin-based peritoneal dialysis fluids by combined UHPLC-DAD and -MS/MS detection. J Pharm Biomed Anal. 2016;118:132–8. https://doi.org/10.1016/j.jpba.2015.10.022.

    Article  CAS  Google Scholar 

  26. Dalpathado DS, Jiang H, Kater MA, Desaire H. Reductive amination of carbohydrates using NaBH(OAC)3. Anal Bioanal Chem. 2005;381(6):1130–7. https://doi.org/10.1007/s00216-004-3028-9.

    Article  CAS  Google Scholar 

  27. Poulter L, Burlingame AL. Desorption mass-spectrometry of oligosaccharides coupled with hydrophobic chromophores. Methods Enzymol. 1990;193:661–88. https://doi.org/10.1016/0076-6879(90)93444-P.

    Article  CAS  Google Scholar 

  28. Zhang HY, Stevens RD, Young SP, Surwit R, Georgiades A, Boston R, et al. A convenient LC-MS method for assessment of glucose kinetics in vivo with D-[13C6] glucose as a tracer. Clin Chem. 2009;55(3):527–32. https://doi.org/10.1373/clinchem.2008.113654.

    Article  CAS  Google Scholar 

  29. Hewavitharana AK. Matrix matching in liquid chromatography-mass spectrometry with stable isotope labelled internal standards—is it necessary? J Chromatogr A. 2011;1218(2):359–61. https://doi.org/10.1016/j.chroma.2010.11.047.

    Article  CAS  Google Scholar 

  30. Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW. Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem. 2004;50(2):423–32. https://doi.org/10.1373/clinchem.2003.026955.

    Article  CAS  Google Scholar 

  31. Basu R, Chandramouli V, Dicke B, Landau B, Rizza R. Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. Diabetes. 2005;54(7):1942–8. https://doi.org/10.2337/diabetes.54.7.1942.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National key R & D program of China (No. 2017YFC0906900), the National Natural Science Foundation of China (No. 21505142), and Yunnan Provincial Science and Technology Department (No. 2012HA015).

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Authors and Affiliations

  1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming, Yunnan, 650201, China

    Lingling Yu, Chao Wen, Xing Li, Shiqi Fang & Kaifeng Hu

  2. School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan, 650091, China

    Lingling Yu

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Chao Wen, Xing Li & Shiqi Fang

  4. Kunming Biomed International, Kunming, Yunnan, 650500, China

    Lichuan Yang & Tony Wang

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  1. Lingling Yu
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Correspondence to Kaifeng Hu.

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All protocols of animal experiments were approved by the Institutional Animal Care and Use Committees at Kunming Biomed International.

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Yu, L., Wen, C., Li, X. et al. Simultaneous quantification of endogenous and exogenous plasma glucose by isotope dilution LC-MS/MS with indirect MRM of the derivative tag. Anal Bioanal Chem 410, 2011–2018 (2018). https://doi.org/10.1007/s00216-018-0872-6

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  • DOI: https://doi.org/10.1007/s00216-018-0872-6

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