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Clinical determination of folates: recent analytical strategies and challenges

  • Jana Verstraete
  • Filip Kiekens
  • Simon Strobbe
  • Hans De Steur
  • Xavier Gellynck
  • Dominique Van Der Straeten
  • Christophe P. StoveEmail author
Review
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry

Abstract

Since the introduction of liquid chromatography tandem mass spectrometry in clinical laboratories, folate analysis has shifted from microbiological or protein-binding assays to chromatographic methods. Now, it is possible to sensitively and selectively determine several folate species in clinical samples where only a total folate content could be quantified using a microbiological or a binding assay. Although several chromatographic methods have been developed, validated, and published, interlaboratory variability limits the comparability of the results. In this review, we provide an overview of the latest strategies for sampling, sample treatment, and analysis and how these may influence the final analytical result. Among the variables covered are the effect of pH, temperature, and storage and the use of antioxidants and anticoagulants on analyte stability. In addition, we highlight the importance of correct assay calibration and the use of (labeled) certified reference materials in order to obtain correct and comparable results among different laboratories.

Graphical abstract

Keywords

Folate Plasma Serum Red blood cell Chromatography Mass spectrometry 

Notes

Funding information

The folate research of the authors was supported by GOA 01G00409 and BOF18/GOA/042 (Bijzonder Onderzoeksfonds UGent), IWT.141529 (Agentschap voor Innovatie door Wetenschap en Technologie), and 1S61617N (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    De Brouwer V, Zhang GF, Storozhenko S, Straeten DV, Lambert WE. pH stability of individual folates during critical sample preparation steps in prevision of the analysis of plant folates. Phytochem Anal. 2007;18(6):496–508.  https://doi.org/10.1002/pca.1006.Google Scholar
  2. 2.
    Osborne CB, Lowe KE, Shane B. Regulation of folate and one-carbon metabolism in mammalian cells. I. Folate metabolism in Chinese hamster ovary cells expressing Escherichia coli or human folylpoly-gamma-glutamate synthetase activity. J Biol Chem. 1993;268(29):21657–64.Google Scholar
  3. 3.
    Scott JM. Folate and vitamin B-12. Proc Nutr Soc. 1999;58(2):441–8.  https://doi.org/10.1017/S0029665199000580.Google Scholar
  4. 4.
    Stover PJ. In: Bailey LB, editor. Folate biochemical pathways and their regulation, in folate in health and disease, vol. 2. Boca-Raton: CRC Press; 2009. p. 49–74.Google Scholar
  5. 5.
    Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011;34(1):75–81.  https://doi.org/10.1007/s10545-010-9177-4.Google Scholar
  6. 6.
    Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr. 2000;72(2):324–32.  https://doi.org/10.1093/ajcn/72.2.324.Google Scholar
  7. 7.
    Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5(11):949–60.  https://doi.org/10.1016/S1474-4422(06)70598-1.Google Scholar
  8. 8.
    Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338(8760):131–137.Google Scholar
  9. 9.
    Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997;94(7):3290–5.  https://doi.org/10.1073/pnas.94.7.3290.Google Scholar
  10. 10.
    Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;4:CD004514.  https://doi.org/10.1002/14651858.CD004514.pub2.Google Scholar
  11. 11.
    Moran RG, Colman PD. Measurement of folylpolyglutamate synthetase in mammalian tissues. Anal Biochem. 1984;140(2):326–42.  https://doi.org/10.1016/0003-2697(84)90174-X.Google Scholar
  12. 12.
    van Haandel L, Becker ML, Williams TD, Stobaugh JF, Leeder JS. Comprehensive quantitative measurement of folate polyglutamates in human erythrocytes by ion pairing ultra-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2012;26(14):1617–30.  https://doi.org/10.1002/rcm.6268.Google Scholar
  13. 13.
    Kiekens F, Van Daele J, Blancquaert D, Van Der Straeten D, Lambert WE, Stove CP. A validated ultra-high-performance liquid chromatography-tandem mass spectrometry method for the selective analysis of free and total folate in plasma and red blood cells. J Chromatogr A. 2015;1398:20–8.  https://doi.org/10.1016/j.chroma.2015.04.025.Google Scholar
  14. 14.
    Wang C, Riedl KM, Schwartz SJ. A liquid chromatography-tandem mass spectrometric method for quantitative determination of native 5-methyltetrahydrofolate and its polyglutamyl derivatives in raw vegetables. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878(29):2949–58.  https://doi.org/10.1016/j.jchromb.2010.08.043.Google Scholar
  15. 15.
    Allen LH. Causes of vitamin B-12 and folate deficiency. Food Nutr Bull. 2008;29(2):S20–34.  https://doi.org/10.1177/15648265080292s105.Google Scholar
  16. 16.
    Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs. 1985;30(2):145–55.  https://doi.org/10.2165/00003495-198530020-00003. Google Scholar
  17. 17.
    Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutr Food Res. 2013;57(4):596–606.  https://doi.org/10.1002/mnfr.201200077.Google Scholar
  18. 18.
    Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111–3.  https://doi.org/10.1038/ng0595-111.Google Scholar
  19. 19.
    Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost. 1998;79(1):119–21.  https://doi.org/10.1055/s-0037-1614230.Google Scholar
  20. 20.
    DeVos L, Chanson A, Liu Z, Ciappio ED, Parnell LD, Mason JB, et al. Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations. Am J Clin Nutr. 2008;88(4):1149–58.  https://doi.org/10.1093/ajcn/88.4.1149.Google Scholar
  21. 21.
    WHO. Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2015.Google Scholar
  22. 22.
    WHO. Nutritional anaemias. In: Report of WHO grup of experts. Geneva: World Health Organization; 1972.Google Scholar
  23. 23.
    WHO. Control of nutritional anaemia with special reference to iron deficiency. Report of an IAEA/USAIS/WHO joint meeting, World Health Organization; 1975.Google Scholar
  24. 24.
    Selhub J, Jacques PF, Dallal G, Choumenkovitch S, Rogers G. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food Nutr Bull. 2008;29(2 Suppl):S67–73.  https://doi.org/10.1177/15648265080292S110.Google Scholar
  25. 25.
    Pfeiffer CM, Hughes JP, Lacher DA, Bailey RL, Berry RJ, Zhang M, et al. Estimation of trends in serum and RBC folate in the U.S. population from pre- to postfortification using assay-adjusted data from the NHANES 1988-2010. J Nutr. 2012;142(5):886–93.  https://doi.org/10.3945/jn.111.156919.Google Scholar
  26. 26.
    WHO. Guideline: optimal serum and red blood cell folate concentration in women of reproductive age for prevention of neural tube defects, World Health Organization; 2015.Google Scholar
  27. 27.
    Pfeiffer CM, Sternberg MR, Hamner HC, Crider KS, Lacher DA, Rogers LM, et al. Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population. Am J Clin Nutr. 2016;104(6):1607–15.  https://doi.org/10.3945/ajcn.116.138529.Google Scholar
  28. 28.
    Konings EJ, Troost FJ, Castenmiller JJ, Roomans HH, Van Den Brandt PA, Saris WH. Intestinal absorption of different types of folate in healthy subjects with an ileostomy. Br J Nutr. 2002;88(3):235–42.  https://doi.org/10.1079/BJN2002613.Google Scholar
  29. 29.
    Bailey LB, Gregory JF 3rd. Folate metabolism and requirements. J Nutr. 1999;129(4):779–82.  https://doi.org/10.1093/jn/129.4.779.Google Scholar
  30. 30.
    Pfeiffer CM, Sternberg MR, Fazili Z, Lacher DA, Zhang M, Johnson CL, et al. Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2. Br J Nutr. 2015;113(12):1965–77.  https://doi.org/10.1017/S0007114515001142.Google Scholar
  31. 31.
    Strandler HS, Patring J, Jagerstad M, Jastrebova J. Challenges in the determination of unsubstituted food folates: impact of stabilities and conversions on analytical results. J Agric Food Chem. 2015;63(9):2367–77.  https://doi.org/10.1021/jf504987n.Google Scholar
  32. 32.
    Akhtar MJ, Khan MA, Ahmad I. Photodegradation of folic acid in aqueous solution. J Pharm Biomed Anal. 1999;19(3–4):269–75.  https://doi.org/10.1016/S0731-7085(98)00038-7.Google Scholar
  33. 33.
    Saubade F, Hemery YM, Guyot JP, Humblot C. Lactic acid fermentation as a tool for increasing the folate content of foods. Crit Rev Food Sci Nutr. 2016.  https://doi.org/10.1080/10408398.2016.1192986.
  34. 34.
    Garbis SD, Melse-Boonstra A, West CE, van Breemen RB. Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Chem. 2001;73(22):5358–64.  https://doi.org/10.1021/ac010741y.Google Scholar
  35. 35.
    Hart DJ, Finglas PM, Wolfe CA, Mellon F, Wright AJ, Southon S. Determination of 5-methyltetrahydrofolate (13C-labeled and unlabeled) in human plasma and urine by combined liquid chromatography mass spectrometry. Anal Biochem. 2002;305(2):206–13.  https://doi.org/10.1006/abio.2002.5662.Google Scholar
  36. 36.
    Rychlik M, Netzel M, Pfannebecker I, Frank T, Bitsch I. Application of stable isotope dilution assays based on liquid chromatography-tandem mass spectrometry for the assessment of folate bioavailability. J Chromatogr B Anal Technol Biomed Life Sci. 2003;792(2):167–76.  https://doi.org/10.1016/S1570-0232(03)00254-X.Google Scholar
  37. 37.
    Kok RM, Smith DE, Dainty JR, Van Den Akker JT, Finglas PM, Smulders YM, et al. 5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism. Anal Biochem. 2004;326(2):129–38.  https://doi.org/10.1016/j.ab.2003.12.003.Google Scholar
  38. 38.
    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. Google Scholar
  39. 39.
    Nelson BC, Pfeiffer CM, Margolis SA, Nelson CP. Solid-phase extraction-electrospray ionization mass spectrometry for the quantification of folate in human plasma or serum. Anal Biochem. 2004;325(1):41–51.  https://doi.org/10.1016/j.ab.2003.10.009.Google Scholar
  40. 40.
    Huang Y, Khartulyari S, Morales ME, Stanislawska-Sachadyn A, Von Feldt JM, Whitehead AS, et al. Quantification of key red blood cell folates from subjects with defined MTHFR 677C>T genotypes using stable isotope dilution liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2008;22(16):2403–12.  https://doi.org/10.1002/rcm.3624.Google Scholar
  41. 41.
    Liu K, Dai X, Zhong D, Deng P, Ma J, Chen X. Simultaneous determination of 6R-leucovorin, 6S-leucovorin and 5-methyltetrahydrofolate in human plasma using solid phase extraction and chiral liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2009;877(10):902–10.  https://doi.org/10.1016/j.jchromb.2009.02.046.Google Scholar
  42. 42.
    Hannisdal R, Ueland PM, Svardal A. Liquid chromatography-tandem mass spectrometry analysis of folate and folate catabolites in human serum. Clin Chem. 2009;55(6):1147–54.  https://doi.org/10.1373/clinchem.2008.114389.Google Scholar
  43. 43.
    Monch S, Netzel M, Netzel G, Rychlik M. Quantitation of folates and their catabolites in blood plasma, erythrocytes, and urine by stable isotope dilution assays. Anal Biochem. 2010;398(2):150–60.  https://doi.org/10.1016/j.ab.2009.11.007.Google Scholar
  44. 44.
    Kirsch SH, Knapp JP, Herrmann W, Obeid R. Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878(1):68–75.  https://doi.org/10.1016/j.jchromb.2009.11.021.Google Scholar
  45. 45.
    Fazili Z, Whitehead RD Jr, Paladugula N, Pfeiffer CM. A high-throughput LC-MS/MS method suitable for population biomonitoring measures five serum folate vitamers and one oxidation product. Anal Bioanal Chem. 2013;405(13):4549–60.  https://doi.org/10.1007/s00216-013-6854-9.Google Scholar
  46. 46.
    Wang X, Zhang T, Zhao X, Guan Z, Wang Z, Zhu Z, et al. Quantification of folate metabolites in serum using ultraperformance liquid chromatography tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2014;962:9–13.  https://doi.org/10.1016/j.jchromb.2014.05.023. Google Scholar
  47. 47.
    Zheng X-H, Jiang L-Y, Zhao L-T, Zhang Q-Y, Ding L. Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC–MS/MS and its application to a pharmacokinetic study. J Pharm Anal. 2015;5:269–75.  https://doi.org/10.1016/j.jpha.2015.05.004.Google Scholar
  48. 48.
    Kopp M, Rychlik M. Quantitation of 5-methyltetrahydrofolic acid in dried blood spots and dried plasma spots by stable isotope dilution assays. PLoS One. 2015;10(11):e0143639.  https://doi.org/10.1371/journal.pone.0143639.Google Scholar
  49. 49.
    Guiraud SP, Montoliu I, Da Silva L, Dayon L, Galindo AN, Corthesy J, et al. High-throughput and simultaneous quantitative analysis of homocysteine-methionine cycle metabolites and co-factors in blood plasma and cerebrospinal fluid by isotope dilution LC-MS/MS. Anal Bioanal Chem. 2017;409(1):295–305.  https://doi.org/10.1007/s00216-016-0003-1.Google Scholar
  50. 50.
    Fazili Z, Pfeiffer CM. Measurement of folates in serum and conventionally prepared whole blood lysates: application of an automated 96-well plate isotope-dilution tandem mass spectrometry method. Clin Chem. 2004;50(12):2378–81.  https://doi.org/10.1373/clinchem.2004.036541. Google Scholar
  51. 51.
    Smith DE, Kok RM, Teerlink T, Jakobs C, Smulders YM. Quantitative determination of erythrocyte folate vitamer distribution by liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med. 2006;44(4):450–9.  https://doi.org/10.1515/CCLM.2006.085.Google Scholar
  52. 52.
    Kirsch SH, Herrmann W, Geisel J, Obeid R. Assay of whole blood (6S)-5-CH3-H4folate using ultra performance liquid chromatography tandem mass spectrometry. Anal Bioanal Chem. 2012;404(3):895–902.  https://doi.org/10.1007/s00216-012-6180-7.Google Scholar
  53. 53.
    Kopp M, Rychlik M. Assessing volumetric absorptive microsampling coupled with stable isotope dilution assay and liquid chromatography-tandem mass spectrometry as potential diagnostic tool for whole blood 5-methyltetrahydrofolic acid. Front Nutr. 2017;4:9.  https://doi.org/10.3389/fnut.2017.00009.Google Scholar
  54. 54.
    Nandania J, Kokkonen M, Euro L, Velagapudi V. Simultaneous measurement of folate cycle intermediates in different biological matrices using liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2018;1092:168–78.  https://doi.org/10.1016/j.jchromb.2018.06.008. Google Scholar
  55. 55.
    O’Broin SD, Gunter EW. Screening of folate status with use of dried blood spots on filter paper. Am J Clin Nutr. 1999;70(3):359–67.  https://doi.org/10.1093/ajcn/70.3.359.Google Scholar
  56. 56.
    Zimmerman RK, Slater ME, Langer EK, Ross JA, Spector LG. Long-term stability of folate in dried blood spots stored in several conditions. J Pediatr. 2013;163(2):596–597 e591.  https://doi.org/10.1016/j.jpeds.2013.03.043.Google Scholar
  57. 57.
    De Kesel PM, Lambert WE, Stove CP. Does volumetric absorptive microsampling eliminate the hematocrit bias for caffeine and paraxanthine in dried blood samples? A comparative study. Anal Chim Acta. 2015;881:65–73.  https://doi.org/10.1016/j.aca.2015.04.056.Google Scholar
  58. 58.
    De Kesel PM, Sadones N, Capiau S, Lambert WE, Stove CP. Hemato-critical issues in quantitative analysis of dried blood spots: challenges and solutions. Bioanalysis. 2013;5(16):2023–41.  https://doi.org/10.4155/bio.13.156.Google Scholar
  59. 59.
    Kok MGM, Fillet M. Volumetric absorptive microsampling: current advances and applications. J Pharm Biomed Anal. 2018;147:288–96.  https://doi.org/10.1016/j.jpba.2017.07.029.Google Scholar
  60. 60.
    Hannisdal R, Ueland PM, Eussen SJ, Svardal A, Hustad S. Analytical recovery of folate degradation products formed in human serum and plasma at room temperature. J Nutr. 2009;139(7):1415–8.  https://doi.org/10.3945/jn.109.105635.Google Scholar
  61. 61.
    Ocke MC, Schrijver J, Obermann-de Boer GL, Bloemberg BP, Haenen GR, Kromhout D. Stability of blood (pro)vitamins during four years of storage at −20 degrees C: consequences for epidemiologic research. J Clin Epidemiol. 1995;48(8):1077–85.  https://doi.org/10.1016/0895-4356(94)00232-F.Google Scholar
  62. 62.
    O'Broin JD, Temperley IJ, Scott JM. Erythrocyte, plasma, and serum folate: specimen stability before microbiological assay. Clin Chem. 1980;26(3):522–4.Google Scholar
  63. 63.
    O’Broin S, Kelleher B. Optimization of erythrocyte folate extraction. Clin Chem. 2001;47(12):2181–2.Google Scholar
  64. 64.
    Patring JDM, Johansson MS, Yazynina E, Jastrebova JA. Evaluation of impact of different antioxidants on stability of dietary folates during food sample preparation and storage of extracts prior to analysis. Anal Chim Acta. 2005;553(1–2):36–42.  https://doi.org/10.1016/j.aca.2005.07.070.Google Scholar
  65. 65.
    Horne DW, Briggs WT, Wagner C. High-pressure liquid chromatographic separation of the naturally occurring folic acid monoglutamate derivatives. Anal Biochem. 1981;116(2):393–7.  https://doi.org/10.1016/0003-2697(81)90378-X.Google Scholar
  66. 66.
    Horne DW. High-performance liquid chromatographic measurement of 5,10-methylenetetrahydrofolate in liver. Anal Biochem. 2001;297(2):154–9.  https://doi.org/10.1006/abio.2001.5334.Google Scholar
  67. 67.
    Schittmayer M, Birner-Gruenberger R, Zamboni N. Quantification of cellular folate species by LC-MS after stabilization by derivatization. Anal Chem. 2018.  https://doi.org/10.1021/acs.analchem.8b00650.
  68. 68.
    Fazili Z, Pfeiffer CM, Zhang M, Jain R. Erythrocyte folate extraction and quantitative determination by liquid chromatography-tandem mass spectrometry: comparison of results with microbiologic assay. Clin Chem. 2005;51(12):2318–25.  https://doi.org/10.1373/clinchem.2005.053801. Google Scholar
  69. 69.
    Stamm RA, Fazili Z, Pfeiffer C. Addition of exogenous γ-glutamyl hydrolase eliminates the need for lengthy incubation of whole blood lysate for quantitation of folate vitamers by high performance liquid chromatography-tandem mass spectrometry. Curr Dev Nutr. 2017.  https://doi.org/10.3945/cdn.117.002055.
  70. 70.
    Natsuhori M, Okada M, Ida R, Sasaki K, Shimoda M, Kokue E. Binding characteristics of folate to high affinity folate binding protein purified from porcine serum. J Vet Med Sci. 1999;61(7):743–8.  https://doi.org/10.1292/jvms.61.743. Google Scholar
  71. 71.
    van Eijsden M, van der Wal MF, Hornstra G, Bonsel GJ. Can whole-blood samples be stored over 24 hours without compromising stability of C-reactive protein, retinol, ferritin, folic acid, and fatty acids in epidemiologic research? Clin Chem. 2005;51(1):230–2.  https://doi.org/10.1373/clinchem.2004.042234. Google Scholar
  72. 72.
    Zhang DJ, Elswick RK, Miller WG, Bailey JL. Effect of serum-clot contact time on clinical chemistry laboratory results. Clin Chem. 1998;44(6 Pt 1):1325–33.Google Scholar
  73. 73.
    Drammeh BS, Schleicher RL, Pfeiffer CM, Jain RB, Zhang M, Nguyen PH. Effects of delayed sample processing and freezing on serum concentrations of selected nutritional indicators. Clin Chem. 2008;54(11):1883–91.  https://doi.org/10.1373/clinchem.2008.108761.Google Scholar
  74. 74.
    Fazili Z, Sternberg MR, Paladugula N, Whitehead RD Jr, Chen H, Pfeiffer CM. The loss of 5-methyltetrahydrofolate in human serum under suboptimal preanalytical conditions can only partially be recovered by an oxidation product. J Nutr. 2014;144(11):1873–9.  https://doi.org/10.3945/jn.114.198358.Google Scholar
  75. 75.
    Hannisdal R, Gislefoss RE, Grimsrud TK, Hustad S, Morkrid L, Ueland PM. Analytical recovery of folate and its degradation products in human serum stored at −25 degrees C for up to 29 years. J Nutr. 2010;140(3):522–6.  https://doi.org/10.3945/jn.109.116418.Google Scholar
  76. 76.
    Jansen EH, Beekhof PK, Cremers JW, Schenk E. Long-term (in)stability of folate and vitamin B12 in human serum. Clin Chem Lab Med. 2012;50(10):1761–3.  https://doi.org/10.1515/cclm-2012-0108.Google Scholar
  77. 77.
    Paladugula N, Fazili Z, Sternberg MR, G G, Pfeiffer C. Serum folate forms are stable during repeated analysis in the presence of ascorbic acid and during frozen sample storage. J Appl Lab Med. 2018;3(3).  https://doi.org/10.1373/jalm.2018.027102.
  78. 78.
    Pfeiffer CM, Fazili Z, Zhang M. Folate analytical methodology. In: Folate in health and disease, vol. 2. Boca-Raton: CRC Press; 2010.Google Scholar
  79. 79.
    Selhub J. Determination of tissue folate composition by affinity chromatography followed by high-pressure ion pair liquid chromatography. Anal Biochem. 1989;182(1):84–93.  https://doi.org/10.1016/0003-2697(89)90722-7.Google Scholar
  80. 80.
    Gregory JF 3rd. Chemical and nutritional aspects of folate research: analytical procedures, methods of folate synthesis, stability, and bioavailability of dietary folates. Adv Food Nutr Res. 1989;33:1–101.  https://doi.org/10.1016/S1043-4526(08)60126-6.Google Scholar
  81. 81.
    Thorpe SJ, Heath A, Blackmore S, Lee A, Hamilton M, O'Broin S, et al. International standard for serum vitamin B(12) and serum folate: international collaborative study to evaluate a batch of lyophilised serum for B(12) and folate content. Clin Chem Lab Med. 2007;45(3):380–6.  https://doi.org/10.1515/CCLM.2007.072.Google Scholar
  82. 82.
    Fazili Z, Pfeiffer CM. Accounting for an isobaric interference allows correct determination of folate vitamers in serum by isotope dilution-liquid chromatography-tandem MS. J Nutr. 2013;143(1):108–13.  https://doi.org/10.3945/jn.112.166769.Google Scholar
  83. 83.
    Owens JE, Holstege DM, Clifford AJ. High-throughput method for the quantitation of total folate in whole blood using LC-MS/MS. J Agric Food Chem. 2007;55(9):3292–7.  https://doi.org/10.1021/jf063648p.Google Scholar
  84. 84.
    Patring JD, Lanina SA, Jastrebova JA. Applicability of alkyl-bonded ultra-pure silica stationary phases for gradient reversed-phase HPLC of folates with conventional and volatile buffers under highly aqueous conditions. J Sep Sci. 2006;29(6):889–904.  https://doi.org/10.1002/jssc.200500481.Google Scholar
  85. 85.
    Vahteristo LT, Ollilainen V, Koivistoinen PE, Varo P. Improvements in the analysis of reduced folate monoglutamates and folic acid in food by high-performance liquid chromatography. J Agric Food Chem. 1996;44(2):477–82.  https://doi.org/10.1021/jf9503467.Google Scholar
  86. 86.
    Ndaw S, Bergaentzle M, Aoude-Werner D, Lahely S, Hasselmann C. Determination of folates in foods by high-performance liquid chromatography with fluorescence detection after precolumn conversion to 5-methyltetrahydrofolates. J Chromatogr A. 2001;928(1):77–90.  https://doi.org/10.1016/S0021-9673(01)01129-3.Google Scholar
  87. 87.
    Bagley PJ, Selhub J. Analysis of folate form distribution by affinity followed by reversed- phase chromatography with electrical detection. Clin Chem. 2000;46(3):404–11.Google Scholar
  88. 88.
    Patring JD, Jastrebova JA. Application of liquid chromatography-electrospray ionisation mass spectrometry for determination of dietary folates: effects of buffer nature and mobile phase composition on sensitivity and selectivity. J Chromatogr A. 2007;1143(1–2):72–82.  https://doi.org/10.1016/j.chroma.2006.12.079.Google Scholar
  89. 89.
    Freisleben A, Schieberle P, Rychlik M. Specific and sensitive quantification of folate vitamers in foods by stable isotope dilution assays using high-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2003;376(2):149–56.  https://doi.org/10.1007/s00216-003-1844-y.Google Scholar
  90. 90.
    De Brouwer V, Storozhenko S, Van de Steene JC, Wille SMR, Stove CP, Van Der Straeten D, et al. Optimisation and validation of a liquid chromatography-tandem mass spectrometry method for folates in rice. J Chromatogr A. 2008;1215(1–2):125–32.  https://doi.org/10.1016/j.chroma.2008.11.004.Google Scholar
  91. 91.
    Pfeiffer CM, Zhang M, Jabbar S. Framework for laboratory harmonization of folate measurements in low- and middle-income countries and regions. Ann N Y Acad Sci. 2018;1414(1):96–108.  https://doi.org/10.1111/nyas.13532.Google Scholar
  92. 92.
    Rogers LM, Cordero AM, Pfeiffer CM, Hausman DB, Tsang BL, De-Regil LM, et al. Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues. Ann N Y Acad Sci. 2018;1431(1):35–57.  https://doi.org/10.1111/nyas.13963.Google Scholar
  93. 93.
    Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL, et al. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(1):303s–12s.  https://doi.org/10.3945/ajcn.111.013011.Google Scholar
  94. 94.
    Fazili Z, Pfeiffer CM, Zhang M, Jain RB, Koontz D. Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on whole-blood folate concentrations measured by LC-MS/MS, microbiologic assay, and bio-rad radioassay. Clin Chem. 2008;54(1):197–201.  https://doi.org/10.1373/clinchem.2007.096545.Google Scholar
  95. 95.
    Fazili Z, Pfeiffer CM, Zhang M. Comparison of serum folate species analyzed by LC-MS/MS with total folate measured by microbiologic assay and Bio-Rad radioassay. Clin Chem. 2007;53(4):781–4.  https://doi.org/10.1373/clinchem.2006.078451.Google Scholar
  96. 96.
    Freisleben A, Schieberle P, Rychlik M. Syntheses of labeled vitamers of folic acid to be used as internal standards in stable isotope dilution assays. J Agric Food Chem. 2002;50(17):4760–8.  https://doi.org/10.1021/jf025571k.Google Scholar
  97. 97.
    Stokvis E, Rosing H, Beijnen JH. Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography/mass spectrometry: necessity or not? Rapid Commun Mass Spectrom. 2005;19(3):401–7.  https://doi.org/10.1002/rcm.1790.Google Scholar
  98. 98.
    Fazili Z, Sternberg MR, Paladugula N, Pfeiffer CM. Two international round-robin studies showed good comparability of 5-methyltetrahydrofolate but poor comparability of folic acid measured in serum by different high-performance liquid chromatography-tandem mass spectrometry methods. J Nutr. 2017;147(9):1815–25.  https://doi.org/10.3945/jn.117.254144.Google Scholar
  99. 99.
    Blakley RL. The biochemistry of folic acid and related pteridines. Amsterdam: North-Holland Publishing Company; 1969.  https://doi.org/10.1002/ange.19700821818.Google Scholar
  100. 100.
    Karayannis MI, Samios DN, Gousetis CP. A study of the molar absorptivity of ascorbic acid at different wavelengths and pH values. Anal Chim Acta. 1977;93(1):275–9.  https://doi.org/10.1016/0003-2670(77)80032-9.Google Scholar
  101. 101.
    Satterfield MB, Sniegoski LT, Sharpless KE, Welch MJ, Hornikova A, Zhang NF, et al. Development of a new standard reference material: SRM 1955 (homocysteine and folate in human serum). Anal Bioanal Chem. 2006;385(3):612–22.  https://doi.org/10.1007/s00216-006-0434-1.Google Scholar
  102. 102.
    Camara JE, Pritchett JS, Daniels YC, Phinney KW, Sander LC. Value assignment of candidate standard reference material® 3949 folate vitamers in frozen human serum by isotope-dilution LC-MS/MS, MSACL 2015 US; 2015.Google Scholar
  103. 103.
    Thorpe SJ, Sands D, Heath AB, Hamilton MS, Blackmore S, Barrowcliffe T. An international standard for whole blood folate: evaluation of a lyophilised haemolysate in an international collaborative study. Clin Chem Lab Med. 2004;42(5):533–9.  https://doi.org/10.1515/CCLM.2004.090.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jana Verstraete
    • 1
  • Filip Kiekens
    • 1
  • Simon Strobbe
    • 2
  • Hans De Steur
    • 3
  • Xavier Gellynck
    • 3
  • Dominique Van Der Straeten
    • 2
  • Christophe P. Stove
    • 1
    Email author
  1. 1.Laboratory of Toxicology, Department of Bio-AnalysisGhent UniversityGhentBelgium
  2. 2.Laboratory of Functional Plant Biology, Department of PhysiologyGhent UniversityGhentBelgium
  3. 3.Division Agri-Food Marketing & Chain Management, Department of Agricultural EconomicsGhent UniversityGhentBelgium

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