Advertisement

Analytical and Bioanalytical Chemistry

, Volume 411, Issue 19, pp 4541–4549 | Cite as

A review of analytical platforms for accurate bile acid measurement

  • Mainak Dutta
  • Jingwei Cai
  • Wei Gui
  • Andrew D. PattersonEmail author
Review
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry

Abstract

Bile acids are acidic steroids which help in lipid absorption, act as signaling molecules, and are key intermediate molecules between host and gut microbial metabolism. Perturbations in the circulating bile acid pool can lead to dysregulated metabolic and immunological function which may be associated with liver and intestinal disease. Bile acids have chemically diverse structures and are present in a broad range of concentrations in a wide variety of samples with complex biological matrices. Advanced analytical methods are therefore required to identify and accurately quantify individual bile acids. Though enzymatic determination of total bile acid is most popular in clinical laboratories, these methods provide limited information about individual bile acids. Advanced analytical methods such as gas chromatography- and liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy are highly informative techniques which help in identification and quantification of individual bile acids in complex biological matrices. Here, we review the detection technologies currently used for bile acid identification and quantification. We further discuss the advantages and disadvantages of these analytical techniques with respect to sensitivity, specificity, robustness, and ease of use.

Graphical abstract

Keywords

Bile acid Mass spectrometry Nuclear magnetic resonance spectroscopy Gas chromatography Liquid chromatography Enzymatic 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013;3(3):1191–212.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009;15(7):804–16.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Guo C, Xie S, Chi Z, Zhang J, Liu Y, Zhang L, et al. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome. Immunity. 2016;45(4):944.PubMedCrossRefGoogle Scholar
  4. 4.
    Gonzalez FJ, Jiang C, Patterson AD. An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease. Gastroenterology. 2016;151(5):845–59.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Wahlström A, Sayin Sama I, Marschall H-U, Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24(1):41–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Sarafian MH, Lewis MR, Pechlivanis A, Ralphs S, McPhail MJW, Patel VC, et al. Bile acid profiling and quantification in biofluids using ultra-performance liquid chromatography tandem mass spectrometry. Anal Chem. 2015;87(19):9662–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Murphy GM, Billing BH, Baron DN. A fluorimetric and enzymatic method for the estimation of serum total bile acids. J Clin Pathol. 1970;23(7):594–8.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Mashige F, Tanaka N, Maki A, Kamei S, Yamanaka M. Direct spectrophotometry of total bile acids in serum. Clin Chem. 1981;27(8):1352–6.PubMedGoogle Scholar
  9. 9.
    Zhang GH, Cong AR, Xu GB, Li CB, Yang RF, Xia TA. An enzymatic cycling method for the determination of serum total bile acids with recombinant 3alpha-hydroxysteroid dehydrogenase. Biochem Biophys Res Commun. 2005;326(1):87–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang X, Zhu M, Xu B, Cui Y, Tian G, Shi Z, et al. Indirect electrochemical detection for total bile acids in human serum. Biosens Bioelectron. 2016;85:563–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Kano M. Human feces bile acids and fractions with enzyme-linked immunosorbent assay. Showa Univ. J. Med. Sci. 1993;5:183–91.CrossRefGoogle Scholar
  12. 12.
    Kobayashi N, Katsumata H, Uto Y, Goto J, Niwa T, Kobayashi K, et al. A monoclonal antibody-based enzyme-linked immunosorbent assay of glycolithocholic acid sulfate in human urine for liver function test. Steroids. 2002;67(10):827–33.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu S, Zhang Y, Qu B, Qin G, Cheng J, Lu F, et al. Detection of total bile acids in biological samples using an indirect competitive ELISA based on four monoclonal antibodies. Anal Methods. 2017;9(4):625–33.CrossRefGoogle Scholar
  14. 14.
    Li T, Apte U. Bile acid metabolism and signaling in cholestasis, inflammation and cancer. Adv Pharmacol. 2015;74:263–302.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Street JM, Setchell KDR. Chromatographic methods for bile acid analysis. Biomed Chromatogr. 1987;2(6):229–41.CrossRefGoogle Scholar
  16. 16.
    Pyka A, Dołowy M. Separation of selected bile acids by TLC. II. One-dimensional and two-dimensional TLC. J Liq Chromatogr Relat Technol. 2004;27(13):2031–8.CrossRefGoogle Scholar
  17. 17.
    Dolowy M. Application of selected topological indices to predict retention parameters of selected bile acids separated on modified TLC plates. Acta Pol Pharm. 2008;65(1):51–7.PubMedGoogle Scholar
  18. 18.
    Shi Y, Xiong J, Sun D, Liu W, Wei F, Ma S, et al. Simultaneous quantification of the major bile acids in artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control. J Sep Sci. 2015;38(16):2753–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Kakiyama G, Muto A, Takei H, Nittono H, Murai T, Kurosawa T, et al. A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS. J Lipid Res. 2014;55(5):978–90.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Onishi S, Itoh S, Ishida Y. Assay of free and glycine- and taurine-conjugated bile acids in serum by high-pressure liquid chromatography by using post-column reaction after group separation. Biochem J. 1982;204(1):135–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Hernanz A, Codoceo R. An improved high-performance liquid-chromatographic determination of conjugated bile acids in serum using paired-ion chromatography. Clin Chim Acta. 1985;145(2):197–203.PubMedCrossRefGoogle Scholar
  22. 22.
    VandenHeuvel WJA, Sweeley CC, Horning EC. Microanalytical separations by gas chromatography in the sex hormone and bile acid series. Biochem Biophys Res Commun. 1960;3(1):33–6.CrossRefGoogle Scholar
  23. 23.
    Batta AK, Salen G. Gas chromatography of bile acids. J Chromatogr B Biomed Sci Appl. 1999;723(1):1–16.PubMedCrossRefGoogle Scholar
  24. 24.
    Griffiths WJ, Sjovall J. Bile acids: analysis in biological fluids and tissues. J Lipid Res. 2010;51(1):23–41.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Yamaga N, Ikebuchi J, Kohara H, Ogura Y, Yamada K. Analysis of bile acids in urine specimens from healthy humans: determination of several bile acids with beta-hydroxyl and carbonyl groups. J Biochem. 1996;119(4):725–30.PubMedCrossRefGoogle Scholar
  26. 26.
    Kimura A, Suzuki M, Murai T, Inoue T, Kato H, Hori D, et al. Perinatal bile acid metabolism: analysis of urinary bile acids in pregnant women and newborns. J Lipid Res. 1997;38(10):1954–62.PubMedGoogle Scholar
  27. 27.
    Mahara R, Takeshita H, Kurosawa T, Ikegawa S, Tohma M. Determination of 1β-hydroxylated bile acids and related compounds in human biological fluids by gas chromatography-mass spectrometry. Anal Sci. 1987;3(5):449–52.CrossRefGoogle Scholar
  28. 28.
    Kumar BS, Chung BC, Lee YJ, Yi HJ, Lee BH, Jung BH. Gas chromatography-mass spectrometry-based simultaneous quantitative analytical method for urinary oxysterols and bile acids in rats. Anal Biochem. 2011;408(2):242–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Ikegawa S, Okuyama H, Oohashi J, Murao N, Goto J. Separation and detection of bile acid 24-glucuronides in human urine by liquid chromatography combined with electrospray ionization mass spectrometry. Anal Sci. 1999;15(7):625–31.CrossRefGoogle Scholar
  30. 30.
    Alnouti Y, Csanaky IL, Klaassen CD. Quantitative-profiling of bile acids and their conjugates in mouse liver, bile, plasma, and urine using LC–MS/MS. J Chromatogr B Anal Technol Biomed Life Sci. 2008;873(2):209–17.CrossRefGoogle Scholar
  31. 31.
    Ikegawa S, Murao N, Motoyama T, Yanagihara T, Niwa T, Goto J. Separation and detection of bile acid 3-glucuronides in human urine by liquid chromatography/electrospray ionization-mass spectrometry. Biomed Chromatogr. 1996;10(6):313–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Shinka T, Inoue Y, Ohse M, Kuhara T. Simple and quantitative analysis of urinary sulfated tauro- and glycodihydroxycholic acids in infant with cholestasis by electrospray ionization mass spectrometry. J. Chromatogr B Anal Technol Biomed Life Sci. 2007;855(1):104–8.CrossRefGoogle Scholar
  33. 33.
    Li Y, Zhang X, Chen J, Feng C, He Y, Shao Y, et al. Targeted metabolomics of sulfated bile acids in urine for the diagnosis and grading of intrahepatic cholestasis of pregnancy. Genes Dis. 2018.Google Scholar
  34. 34.
    Bootsma AH, Overmars H, van Rooij A, van Lint AE, Wanders RJ, van Gennip AH, et al. Rapid analysis of conjugated bile acids in plasma using electrospray tandem mass spectrometry: application for selective screening of peroxisomal disorders. J Inherit Metab Dis. 1999;22(3):307–10.PubMedCrossRefGoogle Scholar
  35. 35.
    Xiang X, Han Y, Neuvonen M, Pasanen MK, Kalliokoski A, Backman JT, et al. Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids and bile acid synthesis marker in humans. Pharmacogenet Genomics. 2009;19(6):447–57.PubMedCrossRefGoogle Scholar
  36. 36.
    Suzuki Y, Kaneko R, Nomura M, Naito H, Kitamori K, Nakajima T, et al. Simple and rapid quantitation of 21 bile acids in rat serum and liver by UPLC-MS-MS: effect of high fat diet on glycine conjugates of rat bile acids. Nagoya J Med Sci. 2013;75(1–2):57–71.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Haag M, Hofmann U, Murdter TE, Heinkele G, Leuthold P, Blank A, et al. Quantitative bile acid profiling by liquid chromatography quadrupole time-of-flight mass spectrometry: monitoring hepatitis B therapy by a novel Na(+)-taurocholate cotransporting polypeptide inhibitor. Anal Bioanal Chem. 2015;407(22):6815–25.PubMedCrossRefGoogle Scholar
  38. 38.
    Krautbauer S, Liebisch G. LC-MS/MS analysis of bile acids. Methods Mol Biol. 1730;2018:103–10.Google Scholar
  39. 39.
    Perwaiz S, Tuchweber B, Mignault D, Gilat T, Yousef IM. Determination of bile acids in biological fluids by liquid chromatography-electrospray tandem mass spectrometry. J Lipid Res. 2001;42(1):114–9.PubMedGoogle Scholar
  40. 40.
    Plumb RS, Rainville PD, Potts WB, 3rd, Johnson KA, Gika E, Wilson ID. Application of ultra performance liquid chromatography-mass spectrometry to profiling rat and dog bile. J Proteome Res 2009;8(5):2495–2500.Google Scholar
  41. 41.
    Hamilton JP, Xie G, Raufman JP, Hogan S, Griffin TL, Packard CA, et al. Human cecal bile acids: concentration and spectrum. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G256–63.PubMedCrossRefGoogle Scholar
  42. 42.
    Hagio M, Matsumoto M, Fukushima M, Hara H, Ishizuka S. Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS. J Lipid Res. 2009;50(1):173–80.PubMedCrossRefGoogle Scholar
  43. 43.
    Cai X, Liu Y, Zhou X, Navaneethan U, Shen B, Guo B. An LC-ESI-MS method for the quantitative analysis of bile acids composition in fecal materials. Biomed Chromatogr. 2012;26(1):101–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Bobeldijk I, Hekman M, de Vries-van der Weij J, Coulier L, Ramaker R, Kleemann R, et al. Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: compound class targeting in a metabolomics workflow. J. Chromatogr B Anal Technol Biomed Life Sci 2008;871(2):306–313.Google Scholar
  45. 45.
    Burkard I, von Eckardstein A, Rentsch KM. Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2005;826(1–2):147–59.CrossRefGoogle Scholar
  46. 46.
    Qiao X, Ye M, Liu CF, Yang WZ, Miao WJ, Dong J, et al. A tandem mass spectrometric study of bile acids: interpretation of fragmentation pathways and differentiation of steroid isomers. Steroids. 2012;77(3):204–11.PubMedCrossRefGoogle Scholar
  47. 47.
    Humbert L, Maubert MA, Wolf C, Duboc H, Mahé M, Farabos D, et al. Bile acid profiling in human biological samples: comparison of extraction procedures and application to normal and cholestatic patients. J Chromatogr B Anal Technol Biomed Life Sci. 2012;899:135–45.CrossRefGoogle Scholar
  48. 48.
    Ando M, Kaneko T, Watanabe R, Kikuchi S, Goto T, Iida T, et al. High sensitive analysis of rat serum bile acids by liquid chromatography/electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal. 2006;40(5):1179–86.PubMedCrossRefGoogle Scholar
  49. 49.
    Ye L, Liu S, Wang M, Shao Y, Ding M. High-performance liquid chromatography-tandem mass spectrometry for the analysis of bile acid profiles in serum of women with intrahepatic cholestasis of pregnancy. J Chromatogr B Anal Technol Biomed Life Sci. 2007;860(1):10–7.CrossRefGoogle Scholar
  50. 50.
    Garcia-Canaveras JC, Donato MT, Castell JV, Lahoz A. Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method. J Lipid Res. 2012;53(10):2231–41.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Scalia S, Games DE. Analysis of conjugated bile acids by packed-column supercritical fluid chromatography. J Chromatogr. 1992;574(2):197–203.PubMedCrossRefGoogle Scholar
  52. 52.
    Ishibashi M, Ando T, Sakai M, Matsubara A, Uchikata T, Fukusaki E, et al. High-throughput simultaneous analysis of pesticides by supercritical fluid chromatography/tandem mass spectrometry. J Chromatogr A. 2012;1266:143–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Taguchi K, Fukusaki E, Bamba T. Simultaneous and rapid analysis of bile acids including conjugates by supercritical fluid chromatography coupled to tandem mass spectrometry. J Chromatogr A. 2013;1299:103–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Scalia S, Games DE. Analysis of conjugated bile acids by on-line supercritical fluid chromatography/thermospra mass spectrometry. Org Mass Spectrom. 1992;27(11):1266–70.CrossRefGoogle Scholar
  55. 55.
    Bettarello L, Bortolini O, Fantin G, Guerrini A. Mixed oxo-hydroxy bile acids as actual or potential impurities in ursodeoxycholic acid preparation: a 1H and 13C NMR study. Farmaco. 2000;55(1):51–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Ishikawa H, Nakashima T, Inaba K, Mitsuyoshi H, Nakajima Y, Sakamoto Y, et al. Proton magnetic resonance assay of total and taurine-conjugated bile acids in bile. J Lipid Res. 1999;40(10):1920–4.PubMedGoogle Scholar
  57. 57.
    Ellul JP, Murphy GM, Parkes HG, Slapa RZ, Dowling RH. Nuclear magnetic resonance spectroscopy to determine the micellar cholesterol in human bile. FEBS Lett. 1992;300(1):30–2.PubMedCrossRefGoogle Scholar
  58. 58.
    Ijare OB, Somashekar BS, Gowda GA, Sharma A, Kapoor VK, Khetrapal CL. Quantification of glycine and taurine conjugated bile acids in human bile using 1H NMR spectroscopy. Magn Reson Med. 2005;53(6):1441–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Duarte IF, Legido-Quigley C, Parker DA, Swann JR, Spraul M, Braumann U, et al. Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS. Mol BioSyst. 2009;5(2):180–90.PubMedCrossRefGoogle Scholar
  60. 60.
    Danese E, Salvagno GL, Negrini D, Brocco G, Montagnana M, Lippi G. Analytical evaluation of three enzymatic assays for measuring total bile acids in plasma using a fully-automated clinical chemistry platform. PLoS One. 2017;12(6):e0179200.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Chavez MN, Krone CL. Silicic acid thin-layer chromatography of conjugated and free bile acids. J Lipid Res. 1976;17(5):545–7.PubMedGoogle Scholar
  62. 62.
    Eneroth P. Thin-layer chromatography of bile acids. J Lipid Res. 1963;4:11–6.PubMedGoogle Scholar
  63. 63.
    Nunes de Paiva MJ, #xe9, Menezes H, Costa C, Cardeal ZDL. Microwave-assisted derivatization of bile acids for gas chromatography/mass spectrometry determination. ISRN Anal. Chem. 2013;2013:6.Google Scholar
  64. 64.
    Amplatz B, Zohrer E, Haas C, Schaffer M, Stojakovic T, Jahnel J, et al. Bile acid preparation and comprehensive analysis by high performance liquid chromatography-high-resolution mass spectrometry. Clin Chim Acta. 2017;464:85–92.PubMedCrossRefGoogle Scholar
  65. 65.
    Ijare OB, Bezabeh T, Albiin N, Bergquist A, Arnelo U, Lindberg B, et al. Simultaneous quantification of glycine- and taurine-conjugated bile acids, total bile acids, and choline-containing phospholipids in human bile using 1H NMR spectroscopy. J Pharm Biomed Anal. 2010;53(3):667–73.PubMedCrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Mainak Dutta
    • 1
  • Jingwei Cai
    • 2
  • Wei Gui
    • 2
  • Andrew D. Patterson
    • 2
    Email author
  1. 1.Department of BiotechnologyBirla Institute of Technology and Science, Pilani, Dubai CampusDubaiUAE
  2. 2.Department of Veterinary and Biomedical SciencesThe Pennsylvania State UniversityState CollegeUSA

Personalised recommendations