Heterocyclic Amines in Foods: Analytical Methods, Formation Mechanism, and Mitigation Strategies

  • Qi Wang
  • Yuge Bi
  • Feng Chen
  • Ka Wing ChengEmail author


During heating of meat-based food products, a group of structurally close compounds collectively known as heterocyclic amines (HAs) can be formed. Drastic heating conditions such as grilling and roasting could lead to significantly higher HA contents. Precursors for this group of polycyclic aromatic compounds are fundamental food components including sugars, amino acids, and creatine, which undergo the Maillard reaction to form HAs [1]. More than two dozen HAs have been identified in thermally processed foods.


  1. 1.
    Skog K, Solyakov A, Jägerstad M (2000) Effects of heating conditions and additives on the formation of heterocyclic amines with reference to amino-carbolines in a meat juice model system. Food Chem 68(3):299–308CrossRefGoogle Scholar
  2. 2.
    Felton J, Knize M (1990) Heterocyclic-amine mutagens/carcinogens in foods. In: Chemical carcinogenesis and mutagenesis I. Springer, Berlin, pp 471–502CrossRefGoogle Scholar
  3. 3.
    Simpson NJ (2000) Solid-phase extraction: principles, techniques, and applications. CRC PressGoogle Scholar
  4. 4.
    Simpson NJK (2000) Solid-phase extraction: principles, techniques, and applications. Marcel Dekker, Inc, New YorkCrossRefGoogle Scholar
  5. 5.
    Zhang Q, Li G, Xiao X (2015) Acrylamide-modified graphene for online micro-solid-phase extraction coupled to high-performance liquid chromatography for sensitive analysis of heterocyclic amines in food samples. Talanta 131:127–135PubMedCrossRefGoogle Scholar
  6. 6.
    Toribio F et al (2000) Comparison of different commercial solid-phase extraction cartridges used to extract heterocyclic amines from a lyophilised meat extract. J Chromatogr A 880(1):101–112PubMedCrossRefGoogle Scholar
  7. 7.
    Shin HS, Strasburg GM, Gray JI (2002) A model system study of the inhibition of heterocyclic aromatic amine formation by organosulfur compounds. J Agric Food Chem 50(26):7684–7690PubMedCrossRefGoogle Scholar
  8. 8.
    Schwarzenbach R, Gubler D (1992) Detection of heterocyclic aromatic amines in food flavours. J Chromatogr A 624(1–2):491–495CrossRefGoogle Scholar
  9. 9.
    Gibis M, Weiss J (2012) Antioxidant capacity and inhibitory effect of grape seed and rosemary extract in marinades on the formation of heterocyclic amines in fried beef patties. Food Chem 134(2):766–774PubMedCrossRefGoogle Scholar
  10. 10.
    Kataoka H (1997) Methods for the determination of mutagenic heterocyclic amines and their applications in environmental analysis. J Chromatogr A 774(1):121–142PubMedCrossRefGoogle Scholar
  11. 11.
    Martin-Calero A et al (2009) Ionic liquids as mobile phase additives in high-performance liquid chromatography with electrochemical detection: application to the determination of heterocyclic aromatic amines in meat-based infant foods. Talanta 79(3):590–597PubMedCrossRefGoogle Scholar
  12. 12.
    Santos FJ et al (2004) Analysis of heterocyclic amines in food products: interlaboratory studies. J Chromatogr B 802(1):69–78CrossRefGoogle Scholar
  13. 13.
    Iwasaki M et al (2010) Heterocyclic amines content of meat and fish cooked by Brazilian methods. J Food Compos Anal 23(1):61–69CrossRefGoogle Scholar
  14. 14.
    Lee K-J et al (2015) Determination of heterocyclic amines and acrylamide in agricultural products with liquid chromatography-tandem mass spectrometry. Toxicol Res 31(3):255PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Fay LB, Ali S, Gross GA (1997) Determination of heterocyclic aromatic amines in food products: automation of the sample preparation method prior to HPLC and HPLC-MS quantification. Mutat Res 376(1–2):29–35PubMedCrossRefGoogle Scholar
  16. 16.
    Messner C, Murkovic M (2004) Evaluation of a new model system for studying the formation of heterocyclic amines. J Chromatogr B 802(1):19–26CrossRefGoogle Scholar
  17. 17.
    Stavric B et al (1997) Mutagenic heterocyclic aromatic amines (HAAs) in ‘processed food flavour’ samples. Food Chem Toxicol 35(2):185–197PubMedCrossRefGoogle Scholar
  18. 18.
    Richling E et al (1997) Analysis of heterocyclic aromatic amines in wine by high-performance liquid chromatography–electrospray tandem mass spectrometry. J Chromatogr A 791(1–2):71–77PubMedCrossRefGoogle Scholar
  19. 19.
    Samy S, Hays MD (2013) Quantitative LC–MS for water-soluble heterocyclic amines in fine aerosols (PM2. 5) at Duke Forest, USA. Atmos Environ 72:77–80CrossRefGoogle Scholar
  20. 20.
    Turesky RJ et al (1988) Analysis of mutagenic heterocyclic amines in cooked beef products by high-performance liquid chromatography in combination with mass spectrometry. Food Chem Toxicol 26(6):501–509PubMedCrossRefGoogle Scholar
  21. 21.
    Fenselau C et al (1985) Correction-comparison of thermospray and fast atom bombardment mass spectrometry as solution-dependent ionization techniques. Anal Chem 57(6):1168–1168CrossRefGoogle Scholar
  22. 22.
    Christian GD (2004) Analytical chemistry. Wiley, HobokenGoogle Scholar
  23. 23.
    Pais P et al (1997) Liquid chromatography-atmospheric-pressure chemical ionization mass spectrometry as a routine method for the analysis of mutagenic amines in beef extracts. J Chromatogr A 778(1):207–218PubMedCrossRefGoogle Scholar
  24. 24.
    Zeng M et al (2014) Effect of six Chinese spices on heterocyclic amine profiles in roast beef patties by ultra performance liquid chromatography-tandem mass spectrometry and principal component analysis. J Agric Food Chem 62(40):9908–9915PubMedCrossRefGoogle Scholar
  25. 25.
    Samy S et al (2013) Speciation and trends of organic nitrogen in southeastern US fine particulate matter (PM2. 5). J Geophys Res Atmos 118(4):1996–2006CrossRefGoogle Scholar
  26. 26.
    Pais P et al (1999) Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings. J Agric Food Chem 47(3):1098–1108PubMedCrossRefGoogle Scholar
  27. 27.
    Skog K, Johansson M, Jägerstad M (1998) Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake. Food Chem Toxicol 36(9–10):879–896PubMedCrossRefGoogle Scholar
  28. 28.
    Shan L et al (2004) Susceptibility of rats to mammary gland carcinogenesis by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) varies with age and is associated with the induction of differential gene expression. Am J Pathol 165(1):191–202PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Archer CL et al (2000) Carcinogenicity of the N-hydroxy derivative of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine, 2-amino-3, 8-dimethyl-imidazo [4, 5-f] quinoxaline and 3, 2′-dimethyl-4-aminobiphenyl in the rat. Cancer Lett 155(1):55–60PubMedCrossRefGoogle Scholar
  30. 30.
    Tang D et al (2007) Grilled meat consumption and PhIP-DNA adducts in prostate carcinogenesis. Cancer Epidemiol Biomarkers Prev 16(4):803–808PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Shin A et al (2007) Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee colorectal polyp study. Int J Cancer 121(1):136–142PubMedCrossRefGoogle Scholar
  32. 32.
    Jagerstad M et al (1998) Chemistry, formation and occurrence of genotoxic heterocyclic amines identified in model systems and cooked foods. Zeitschrift Fur Lebensmittel-Untersuchung Und -Forschung a-Food Res Technol 207(6):419–427CrossRefGoogle Scholar
  33. 33.
    Weisburger JH (2005) Specific maillard reactions yield powerful mutagens and carcinogens. In: Labuza TP et al (eds) Maillard reactions in chemistry, food and health. Woodhead Publishing, Cambridge, pp 335–340CrossRefGoogle Scholar
  34. 34.
    Skog K et al (1997) Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues. Food Chem Toxicol 35(6):555–565PubMedCrossRefGoogle Scholar
  35. 35.
    Aaslyng MD et al (2013) Content of heterocyclic amines and polycyclic aromatic hydrocarbons in pork, beef and chicken barbecued at home by Danish consumers. Meat Sci 93(1):85–91PubMedCrossRefGoogle Scholar
  36. 36.
    Milić BL, Djilas SM, C̆anadanović-Brunet JM (1993) Synthesis of some heterocyclic aminoimidazoazarenes. Food Chem 46(3):273–276CrossRefGoogle Scholar
  37. 37.
    Cheng KW et al (2009) Inhibition of mutagenic PhIP formation by epigallocatechin gallate via scavenging of phenylacetaldehyde. Mol Nutr Food Res 53(6):716–725PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang X et al (2015) The colorants, antioxidants, and toxicants from nonenzymatic browning reactions and the impacts of dietary polyphenols on their thermal formation. Food Funct 6(2):345–355PubMedCrossRefGoogle Scholar
  39. 39.
    Dashwood RH (2002) Modulation of heterocyclic amine-induced mutagenicity and carcinogenicity: an ‘A-to-Z’ guide to chemopreventive agents, promoters, and transgenic models. Mutat Res/Rev Mutat Res 511(2):89–112CrossRefGoogle Scholar
  40. 40.
    Turesky RJ, Marchand LL (2011) Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol 24(8):1169–1214PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Shimada T et al (2013) Metabolic activation of polycyclic aromatic hydrocarbons and aryl and heterocyclic amines by human cytochromes P450 2A13 and 2A6. Chem Res Toxicol 26(4):529–537PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lan CM, Chen BH (2002) Effects of soy sauce and sugar on the formation of heterocyclic amines in marinated foods. Food Chem Toxicol 40(7):989–1000PubMedCrossRefGoogle Scholar
  43. 43.
    Kikugawa K, Hiramoto K, Kato T (2000) Prevention of the formation of mutagenic and/or carcinogenic heterocyclic amines by food factors. Biofactors 12(1–4):123–127PubMedCrossRefGoogle Scholar
  44. 44.
    Skog K, Jägerstad M, Reuterswärd AL (1992) Inhibitory effect of carbohydrates on the formation of mutagens in fried beef patties. Food Chem Toxicol 30(8):681–688PubMedCrossRefGoogle Scholar
  45. 45.
    Hasnol ND, Jinap S, Sanny M (2014) Effect of different types of sugars in a marinating formulation on the formation of heterocyclic amines in grilled chicken. Food Chem 145:514–521PubMedCrossRefGoogle Scholar
  46. 46.
    Chen C (1988) East Lansing. Michigan State UniversityGoogle Scholar
  47. 47.
    Lan C, Kao T, Chen B (2004) Effects of heating time and antioxidants on the formation of heterocyclic amines in marinated foods. J Chromatogr B 802(1):27–37CrossRefGoogle Scholar
  48. 48.
    Johansson MAE, Jägerstad M (1996) Influence of pro- and antioxidants on the formation of mutagenic-carcinogenic heterocyclic amines in a model system. Food Chem 56(1):69–75CrossRefGoogle Scholar
  49. 49.
    Pearson AM et al (1992) Mechanism(s) involved in meat mutagen formation and inhibition. Free Radic Biol Med 13(2):161–167PubMedCrossRefGoogle Scholar
  50. 50.
    Vitaglione P, Fogliano V (2004) Use of antioxidants to minimize the human health risk associated to mutagenic/carcinogenic heterocyclic amines in food. J Chromatogr B 802(1):189–199CrossRefGoogle Scholar
  51. 51.
    Shin H-S (2005) Influence of food ingredients on the formation of heterocyclic aromatic amine in cooked pork patties. Food Sci Biotechnol 14(5):572–575Google Scholar
  52. 52.
    Cheng KW, Chen F, Wang M (2007) Inhibitory activities of dietary phenolic compounds on heterocyclic amine formation in both chemical model system and beef patties. Mol Nutr Food Res 51(8):969–976PubMedCrossRefGoogle Scholar
  53. 53.
    Kolpe U et al (2002) Turmeric and curcumin prevents the formation of mutagenic Maillard reaction products. Int Congr Ser 1245:327–334CrossRefGoogle Scholar
  54. 54.
    Persson E et al (2003) Influence of antioxidants in virgin olive oil on the formation of heterocyclic amines in fried beefburgers. Food Chem Toxicol 41(11):1587–1597PubMedCrossRefGoogle Scholar
  55. 55.
    Cheng KW, Chen F, Wang M (2006) Heterocyclic amines: chemistry and health. Mol Nutr Food Res 50(12):1150–1170PubMedCrossRefGoogle Scholar
  56. 56.
    K, K (1999) Involvement of free radicals in the formation of heterocyclic amines and prevention by antioxidants. Cancer Lett 143(2):123–126CrossRefGoogle Scholar
  57. 57.
    Cheng KW et al (2008) Trapping of Phenylacetaldehyde as a key mechanism responsible for Naringenin’s inhibitory activity in mutagenic 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine formation. Chem Res Toxicol 21(10):2026–2034PubMedCrossRefGoogle Scholar
  58. 58.
    Zhu Q et al (2016) Inhibitory effects of selected dietary flavonoids on the formation of total heterocyclic amines and 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in roast beef patties and in chemical models. Food Funct 7(2):1057–1066PubMedCrossRefGoogle Scholar
  59. 59.
    Murkovic M, Steinberger D, Pfannhauser W (1998) Antioxidant spices reduce the formation heterocyclic amines in fried meat. Zeitschrift für Lebensmitteluntersuchung und -Forschung A 207(6):477–480CrossRefGoogle Scholar
  60. 60.
    S, J et al (2016) Heterocyclic aromatic amines in deep fried lamb meat: the influence of spices marination and sensory quality. J Food Sci Technol 53(3):1411–1417CrossRefGoogle Scholar
  61. 61.
    Khan MR et al (2017) Effect of natural food condiments on carcinogenic/mutagenic heterocyclic amines formation in thermally processed camel meat. J Food Process Preserv 41(1):e12819CrossRefGoogle Scholar
  62. 62.
    Cheng KW et al (2007) Inhibitory effect of fruit extracts on the formation of heterocyclic amines. J Agric Food Chem 55(25):10359–10365PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Qi Wang
    • 1
    • 2
  • Yuge Bi
    • 1
    • 2
  • Feng Chen
    • 1
    • 2
  • Ka Wing Cheng
    • 1
    • 2
    Email author
  1. 1.Institute for Advanced StudyShenzhen UniversityShenzhenChina
  2. 2.Institute for Food & Bioresource Engineering, College of EngineeringPeking UniversityBeijingChina

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