Recent developments in fatty acids profile determination in biological samples - a review

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The present paper is a literature review of the recent years dealing with the most important separation techniques of fatty acids in biological samples. Our aim was to make a synthesis of the analytical methods used, to note the most used ones, but also to mention other methods that are less utilized, which can have important advantages (such as less time consuming, greener reagents, etc.). Gas-chromatographic separation methods were described and compared to liquid chromatographic separations of fatty acids in different types of biological samples. In the same time, the importance of determining fatty acids profiles in biological samples was revealed, pointing out the possible implications in diagnostics of different types of disorders or remarking different profiles compared to healthy states.

1. Nishi SK, Kendall CWC, Bazinet RP, Bashyam B, Ireland C, Augustin LS, et al. Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes. Nutr Metab Cardiovasc Dis. 2014 Aug;24(8):845–52. DOI: 10.1016/j.numecd.2014.04.001

2. Taha AY, Cheon Y, Ma K, Rapoport SI, Rao JS. Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients. J Psychiatr Res 2013 May;47(5):636–43. DOI: 10.1016/j.jpsychires.2013.01.016

3. Johnson M, Månsson JE, Ostlund S, Fransson G, Areskoug B, Hjalmarsson K, et al. Fatty acids in ADHD: plasma profiles in a placebo-controlled study of Omega 3/6 fatty acids in children and adolescents. Atten Defic Hyperact Disord. 2012 Dec;4(4):199–204. DOI: 10.1007/s12402-012-0084-4

4. Hama K, Nagai T, Nishizawa C, Ikeda K, Morita M, Satoh N, et al. Molecular species of phospholipids with very long chain fatty acids in skin fibroblasts of Zellweger syndrome. Lipids 2013. Dec;48(12):1253–67.

5. Han LD, Xia JF, Liang QL, Wang Y, Wang YM, Hu P, et al. Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography-mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy. Anal Chim Acta. 2011 Mar;689(1):85–91. DOI: 10.1016/j.aca.2011.01.034

6. Sertoglu E, Kurt I, Tapan S, Uyanik M, Serdar M, Kayadibi H, et al. Comparison of plasma and erythrocyte membrane fatty acid compositions in patients with end-stage renal disease and type 2 diabetes mellitus. Chem Phys Lipids. 2014 Mar;178:11–7. DOI: 10.1016/j.chemphyslip.2013.12.011

7. Chuang CK, Yeung CY, Jim WT, Lin SP, Wang TJ, Huang SF, et al. Comparison of free fatty acid content of human milk from Taiwanese mothers and infant formula. Taiwan J Obstet Gynecol. 2013 Dec;52(4):527–33. DOI: 10.1016/j.tjog.2013.10.013

8. Cruz-Hernandez C, Goeuriot S, Giuffrida F, Thakkar SK, Destaillats F. Direct quantification of fatty acids in human milk by gas chromatography. J Chromatogr A. 2013 Apr;1284:174–9. DOI: 10.1016/j.chroma.2013.01.094

9. Kremmyda LS, Vlachava M, Noakes PS, Diaper ND, Miles E, Calder PC. Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review. Clin Rev Allergy Immunol. 2011 Aug;41(1):36–66. DOI: 10.1007/s12016-009-8186-2

10. Fontes JD, Rahman F, Lacey S, Larson MG, Vasan RS, Benjamin EJ, et al. Red blood cell fatty acids and biomarkers of inflammation: A cross-sectional study in a community-based cohort. Atherosclerosis. 2015 Jun;240(2):431–6. DOI: 10.1016/j.atherosclerosis.2015.03.043

11. Payeur AL, Lorenz M, Kennedy RT. Analysis of fatty acid composition in insulin secreting cells by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2012 Apr;893-894:187–92. DOI: 10.1016/j.jchromb.2012.03.003

12. Mal M, Koh PK, Cheah PY, Chan ECY. Metabotyping of human colorectal cancer using two-dimensional gas chromatography mass spectrometry. Anal Bioanal Chem 2012 Apr;403(2):483–93. DOI: 10.1007/s00216-012-5870-5

13. Zhang J, Zhang L, Ye X, Chen L, Zhang L, Gao Y, et al. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostaglandins Leukot Essent Fat Acids. 2013 May;88(5):355–60. DOI: 10.1016/j.plefa.2013.02.005

14. Zhang XJ, Huang LL, Su H, Chen YX, Huang J, He C, et al. Characterizing plasma phospholipid fatty acid profiles of polycystic ovary syndrome patients with and without insulin resistance using GC-MS and chemometrics approach. J Pharm Biomed Anal. 2014 Jul;95:85–92. DOI: 10.1016/j.jpba.2014.02.014

15. Jurczyszyn A, Czepiel J, Gdula-Argasińska J, Czapkiewicz A, Biesiada G, Dróżdż M, et al. Erythrocyte membrane fatty acids in multiple myeloma patients. Leuk Res. 2014 Oct;38(10):1260–5. DOI: 10.1016/j. leukres.2014.08.009

16. Wang SH, Hung HC, Tsai CC, Huang MC, Ho KY, Wu YM, et al. Plasma polyunsaturated fatty acids and periodontal recovery in Taiwanese with periodontitis: A significant relationship. Arch Oral Biol. 2014 Aug;59(8):800–7. DOI: 10.1016/j.archoralbio.2014.04.009

17. Takahashi T, Yoshida S. Distribution of Glycolipid and Unsaturated Fatty Acids in Human Hair. Lipids. 2014 Sep;49(9):905–17. DOI: 10.1007/s11745-014-3937-0

18. Enke U, Jaudszus A, Schleussner E, Seyfarth L, Jahreis G, Kuhnt K. Fatty acid distribution of cord and maternal blood in human pregnancy: special focus on individual trans fatty acids and conjugated linoleic acids. Lipids Health Dis. 2011 Dec;10(1):247. DOI: 10.1186/1476-511X-10-247

19. Wang DC, Sun CH, Liu LY, Sun XH, Jin XW, Song WL, et al. Serum fatty acid profiles using GC-MS and multivariate statistical analysis: potential biomarkers of Alzheimer’s disease. Neurobiol Aging. 2012 Jun;33(6):1057–66. DOI: 10.1016/j.neurobiolaging.2010.09.013

20. Castro-Gómez P, Fontecha J, Rodríguez-Alcalá LM. A high-performance direct transmethylation method for total fatty acids assessment in biological and foodstuff samples. Talanta. 2014 Oct;128:518–23. DOI: 10.1016/j.talanta.2014.05.051

21. Ecker J, Scherer M, Schmitz G, Liebisch G. A rapid GCMS method for quantification of positional and geometric isomers of fatty acid methyl esters. J Chromatogr B. Anal Technol Biomed Life Sci. 2012 May;897:98–104. DOI: 10.1016/j.jchromb.2012.04.015

22. Kopf T, Schmitz G. Analysis of non-esterified fatty acids in human samples by solid-phase-extraction and gas chromatography/mass spectrometry. J Chromatogr B. 2013 Nov;938:22–6. DOI: 10.1016/j. jchromb.2013.08.016

23. Wang F, Xiong X, Guo X, Wang H, Zhang H. Determination of fatty acids in bio-samples based on the pre-column fluorescence derivatization with 1,3,5,7-tetramethyl-8-butyrethylenediamine-difluoroboradia-za-s-indacene by high performance liquid chromatography. J Chromatogr A. 2013 May;1291:84–91. DOI: 10.1016/j.chroma.2013.03.062 DOI: 10.1016/j.chroma.2012.12.045

24. Lin L, Yang H, Jones PJH. Quantitative analysis of multiple fatty acid ethanolamides using ultra-performance liquid chromatography–tandem mass spectrometry. Prostaglandins Leukot Essent Fat Acids. 2012 Dec;87(6):189–95. DOI: 10.1016/j.plefa.2012.09.001

25. Mori N, Fukano Y, Arita R, Shirakawa R, Kawazu K, Nakamura M, et al. Rapid identification of fatty acids and (O-acyl)-ω-hydroxy fatty acids in human meibum by liquid chromatography/high-resolution mass spectrometry. J Chromatogr A. 2014 Jun;1347:129–36. DOI: 10.1016/j.chroma.2014.04.082

26. Aslan M, Aslan I, Özcan F, Eryılmaz R, Ensari CO, Bilecik T. A pilot study investigating early postoperative changes of plasma polyunsaturated fatty acids after laparoscopic sleeve gastrectomy. Lipids Health Dis. 2014 Jan;13:62. DOI: 10.1186/1476-511X-13-62

27. Guo XF, Li Y, Wang H, Zhang HS. Determination of Fatty Acids in Saliva of Smokers and Nonsmokers by HPLC with Fluorescence Detection Using a Hydrazine-Based Difluoro-boraindacene Reagent. Chromatographia. 2014 Feb;77(5-6):431–8. DOI: 10.1007/s10337-014-2627-7

28. Katrangi W, Lawrenz J, Seegmiller AC, Laposata M. Interactions of linoleic and alpha-linolenic acids in the development of fatty acid alterations in cystic fibrosis. Lipids. 2013 Apr;48(4):333–42. DOI: 10.1007/s11745-013-3768-4

29. Aslan M, Celmeli G, Ozcan F, Kupesiz A. LC-MS/MS analysis of plasma polyunsaturated fatty acids in patients with homozygous sickle cell disease. Clin Exp Med. 2014 Aug; 15(3):397-403 DOI: 10.1007/s10238-014-0293-6

30. Dasilva G, Pazos M, Gallardo JM, Rodríguez I, Cela R, Medina I. Lipidomic analysis of polyunsaturated fatty acids and their oxygenated metabolites in plasma by solid-phase extraction followed by LC-MS. Anal Bioanal Chem. 2014 May;406(12):2827–39. DOI: 10.1007/s00216-014-7701-3

31. Trufelli H, Famiglini G, Termopoli V, Cappiello A. Profiling of non-esterified fatty acids in human plasma using liquid chromatography-electron ionization mass spectrometry. Anal Bioanal Chem. 2011 Jul;400(9):2933–41. DOI: 10.1007/s00216-011-4955-x

32. Mendonça P, Barra DC, Macêdo M, Stremel M, Fett R, Amadeu G, et al. A rapid method for monitoring total trans fatty acids (TTFA) during industrial manufacturing of Brazilian spreadable processed cheese by capillary zone electrophoresis. Food Control. 2012 Feb;23(2):456–61. DOI: 10.1016/

33. Stiebing C, Matthäus C, Krafft C, Keller AA, Weber K, Lorkowski S, et al. Complexity of fatty acid distribution inside human macrophages on single cell level using Raman micro-spectroscopy. Anal Bioanal Chem. 2014 Nov;406(27):7037-46. DOI: 10.1007/s00216-014-7927-0

34. Khedr A, Hegazy M, Kamal A, Shehata M. Profiling of esterified fatty acids as biomarkers in the blood of dengue fever patients using a microliter-scale extraction followed by gas chromatography and mass spectrometry. J Sep Sci. 2015 Jan;38(2):316–24. DOI: 10.1002/jssc.201400749

35. Yu S, Dong J, Zhou W, Yang R, Li H, Zhao H, et al. A rapid and precise method for quantification of fatty acids in human serum cholesteryl esters by liquid chromatography and tandem mass spectrometry. J Chromatogr B. 2014 Jun;960:222–9. DOI: 10.1016/j. jchromb.2014.04.040

36. Kortz L, Dorow J, Becker S, Thiery J, Ceglarek U. Fast liquid chromatography-quadrupole linear ion trap-mass spectrometry analysis of polyunsaturated fatty acids and eicosanoids in human plasma. J Chromatogr B Anal Technol Biomed Life Sci. 2013 May;927:209–13. DOI: 10.1016/j.jchromb.2013.03.012

37. Wong YF, Saad B, Makahleh A. Capillary electrophoresis with capacitively coupled contactless conductivity detection for the determination of cis/trans isomers of octadec-9-enoic acid and other long chain fatty acids. J Chromatogr A. 2013 May;1290:82–90. DOI: 10.1016/j.chroma.2013.03.014

38. Takahashi T, Yoshida S. Distribution of glycolipid and unsaturated Fatty acids in human hair. Lipids. 2014 Sep;49(9):905–17. DOI: 10.1007/s11745-014-3937-0

39. Tremblay-Franco M, Zerbinati C, Pacelli A, Palmaccio G, Lubrano C, Ducheix S, et al. Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human. Steroids. 2015 May;99:287–92. DOI: 10.1016/j.steroids.2015.03.019

40. Arakawa K, Himeno H, Kirigaya J, Otomo F, Matsushita K, Nakahashi H, et al. Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion injury and progression of myocardial damage after reperfusion in patients with ST-segment elevation acute myocardial infarction. J Cardiol. 2015 Aug;66(2):101–7. DOI: 10.1016/j.jjcc.2015.03.009

41. Sherry CL, Oliver JS, Marriage BJ. Docosahexaenoic acid supplementation in lactating women increases breast milk and plasma docosahexaenoic acid concentrations and alters infant omega 6:3 fatty acid ratio. Prostaglandins, Leukot Essent Fat Acids. 2015 Apr;95:63–9. DOI: 10.1016/j.plefa.2015.01.005

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Romanian Journal of Laboratory Medicine

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