Determination of 5-hydroxymethylfurfural (5-HMF) in Expired Pharmaceutical Syrups by Using HPLC-DAD Method

Year 2018, Volume: 5 Issue: 3, 1431 - 1440, 01.09.2018

Songül Ünüvar

https://doi.org/10.18596/jotcsa.477710

Cited By: 7

Abstract

The Maillard reaction product
5-hydroxymethylfurfural (5-HMF) is formed under acidic conditions by the
dehydration of sugars in carbohydrate-based food and pharmaceutical products
during heating and storage. As pharmaceutical syrup formulations contain sugar
and are stored under room temperature, they provide favorable conditions for
the formation of 5-HMF. The long-term storage of syrup bottles after their cap
has been opened and the unintentional use of expired syrups can lead to the
formation of undesirable products such as 5-HMF in medications. Although legal
limits have been established for 5-HMF content in pharmaceutical preparations,
these levels may exceed those limits in hot climates or under inappropriate
storage conditions. The present study detects and measures 5-HMF levels in
expired pharmaceutical syrups through the HPLC-DAD (High Performance Liquid
Chromatography with Diode Array Detection) method, and investigates the effects
on 5-HMF levels of the 72-hour storage of syrups at temperatures of 40˚C. The
5-HMF level in syrups stored at room temperature varied between 1.34 μg/mL to
15.63 μg/mL, while in syrups stored at higher temperatures, the levels ranged
from 2.24 μg/mL to 18.24 μg/mL. This indicated that 5-HMF content in syrups
stored at 40 ˚C was higher than those measured in syrups stored at room
temperature, although the increase was not found to be statistically
significant (p>0.05). In addition to measuring the amount of 5-HMF in
pharmaceutical syrups, this study also examined the changes in the levels of
this dehydration product in syrup formulations under hot climates and according
to storage conditions.

Keywords

5-hydroxymethylfurfural, pharmaceutical syrup, HPLC-DAD, exposure, expiration date

References

• 1. National Center for Biotechnology Information. PubChem Compound Database; CID=237332, https://pubchem.ncbi.nlm.nih.gov/compound/237332 (accessed July 3, 2018).
• 2. Zakrzewska ME, Bogel-Lukasik E. Bogel-Lukasik R. Ionic Liquid-Mediated Formation of 5-hydroxymethylfurfural - a Promising Biomass-Derived Building Block. Chem Rev. 2011;111(2):397-417.
• 3. Brode GL, Mark HF, Othmer DF, Overberger CG, Seaborg GT, Grayson M. In Encyclopedia of Chemical Technology, Kirk RE, Othmer DF, Eds. Wiley, New York, 1982;17:411-13.
• 4. Larousse C, Rigal L, Gaset A. Synthesis of 5,5′-oxydimethyl bis (2-furfural) by Thermal Dehydratation of 5-hydroxymethyl Furfural in the Presence of Dimethylsulfoxide. J Chem Technol Biotechnol. 1992;53(1):111-16.
• 5. Kunz M. Hydroxymethylfurfural, a Possible Basic Chemical Industrial Intermediates. In Inulin and Inulin-Containing Crops, Fuchs A, Ed. Elsevier Science Publishers, Amsterdam, The Netherlands, 1993;3:149-160.
• 6. Morales FJ. Hydroxymethylfurfural (HMF) and related compounds. Process-Induced Food Toxicants: Occurence, Formation, Mitigation and Health Risks, (eds: Stadler, R H, Lineback DR), A john Wiley & Sons Inc Publications, 2009.
• 7. Ruiz-Matute AI, Weiss M, Sammataro D, Finely J, Sanz ML. Carbohydrate Composition of High-Fructose Corn Syrups (HFCS) Used for Bee Feeding: Effect on Honey Composition. J Agric Food Chem. 2010;58(12):7317-22.
• 8. Arribas-Lorenzo G, Morales FJ. Estimation of Dietary Intake of 5-hydroxymethylfurfural and Related Substances From Coffee to Spanish Population. Food Chem Toxicol. 2010;48(2):644-9.
• 9. Husøy T, Haugen M, Murkovic M, Jöbstl D, Stølen LH, Bjellaas T, Rønningborg C, Glatt H, Alexander J. Dietary Exposure to 5-hydroxymethylfurfural From Norwegian Food and Correlations with Urine Metabolites of Short-term Exposure. Food Chem Toxicol. 2008;46(12):3697-3702.
• 10. Rufían-Henares JA, de la Cueva SP. Assessment of Hydroxymethylfurfural Intake in the Spanish Diet. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008;25(11):1306-12.
• 11. NTP, Testing Status of Agents at NTP. 5-(Hydroxymethyl)-2-furfural. Nomination Background. Washington, DC: National Toxicology Program, Dept Health Human Serv. https://ntp.niehs.nih.gov/testing/noms/search/summary/nm-n95002.html (accessed May 18, 2018).
• 12. Gökmen V, Senyuva HZ. Improved Method for the Determination of Hydroxymethylfurfural in Baby Foods Using Liquid Chromatography-mass Spectrometry. J Agric Food Chem. 2006;54(8):2845-9.
• 13. Delgado-Andrade C, Seiquer I, Navarro MP, Morales FJ. Maillard Reaction Indicators in Diets Usually Consumed by Adolescent Population. Mol Nutr Food Res. 2007;51(3):341-51.
• 14. Abraham K, Gürtler R, Berg K, Heinemeyer G, Lampen A, Appel KE. Toxicology and Risk Assessment of 5-Hydroxymethylfurfural in Food. Mol Nutr Food Res. 2011;55(5):67-78.
• 15. Hewala II, Blaih SM,nZoweil AM, Onsi SM. Detection and Determination of Interfering 5-hydroxymethylfurfural in the Analysis of Caramel-coloured Pharmaceutical Syrups. J Clin Pharm Ther. 1993;18(1):49-53.
• 16. Ghaderi F, Shadbad MRS, Hoseinzadehm. Effect of pH and Storage Temperature on 5-(hydroxymethyl) Furfural (5HMF) Formation in USP Syrup Preparation. Pharm Sci. 2015;21(1):1-5.
• 17. Shapla UM, Solayman M, Alam N, Khalil MI, Gan SH. 5-Hydroxymethylfurfural (HMF) Levels in Honey and Other Food Products: Effects on Bees and Human Health. Chem Cent J. 2018;12(1):35.
• 18. Zappalà M, Fallico B, Arena E, Verzera A. Methods for the Determination of HMF in Honey: a Comparison. Food Control. 2005;16(3):273-277.
• 19. Sivakesava S, Irudayaraj J. A Rapid Spectroscopic Technique for Determining Honey Adulteration with Corn Syrup Direct Electrochemical Determination of Hydroxymethylfurfural (HMF) and its Application to Honey Samples. J Food Sci. 2001;66(6):787-792.
• 20. IHC, The International Honey Commission. Bogdanov S. 1999; 1–54. http://www.ihc-platform.net/ihcmethods2009.pdf (accessed October 18, 2018).
• 21. Wootton M, Ryall L. A Comparison of Codex Alimentarius Commission and HPLC Methods for 5-hydroxymethyl-2-furaldehyde Determination in Honey. J Apic Res. 1985;24(2):120124.
• 22. Reyes‐Salas EO, Manzanilla‐Cano JA, Barceló‐Quintal MH, Juárez‐Mendoza D, Reyes‐Salas M. Direct Electrochemical Determination of Hydroxymethylfurfural (HMF) and its Application to Honey Samples. Anal Lett. 2006;39(1):161-171.
• 23. Yuan JP, Chen F. Separation and Identification of Furanic Compounds in Fruit Juices and Drinks by High-performance Liquid Chromatography Photodiode Array Detection. J Agric Food Chem. 1998;46:1286-1291.
• 24. De la Iglesia F, Lázaro F, Puchades R, Maquieira A. Automatic Determination of 5-hydroxymethylfurfural (5-HMF) by a Flow Injection Method. Food Chem. 1997;60(2):245-250.
• 25. Rizelio VM, Gonzaga LV, Borges GdSC, Micke GA, Fett R, Costa ACO. Development of a Fast MECK Method for Determination of 5-HMF in Honey Samples. Food Chem. 2012;133:1640-1645.
• 26. Rajchl A, Drgová L, Grégrová A, Čížková H, Ševčík R, Voldřich M. Rapid Determination of 5-hydroxymethylfurfural by DART Ionization with Time-of-flight Mass Spectrometry. Anal Bioanal Chem. 2013;405:4737-4745.
• 27. Jeurings J, Kuppers F. High Performance Liquid Chromatography of Furfural and Hydroxymethylfurfural in Spirits and Honey. J Assoc Off Anal Chem. 1980;63(6):1215-8.
• 28. Durling LJ, Busk L, Hellman BE. Evaluation of the DNA Damaging Effect of the Heat-induced Food Toxicant 5-hydroxymethylfurfural (HMF) in Various Cell Lines with Different Activities of Sulfotransferases. Food Chem Toxicol. 2009;47(4):880-4.
• 29. Murkovic M, Pichler N. Analysis of 5-hydroxymethylfurfual in Coffee, Dried Fruits and Urine. Mol Nutr Food Res. 2006;50(9):842-6.
• 30. Bakhiya N, Monien B, Frank H, Seidel A, Glatt H. Renal Organic Anion Transporters OAT1 and OAT3 Mediate the Cellular Accumulation of 5 Sulfooxymethylfurfural, a Reactive, Nephrotoxic Metabolite of the Maillard Product 5-hydroxymethylfurfural. Biochem Pharmacol. 2009;78(4):414-9.
• 31. Severin I, Dumont C, Jondeau-Cabaton A, Graillot V, Chagnon MC. Genotoxic Activities of the Food Contaminant 5-hydroxymethylfurfural Using Different in Vitro Bioassays. Toxicol Lett. 2010;192(2):189-94.
• 32. Svendsen C, Husoy T, Glatt H, Paulsen JE, Alexander J. 5-Hydroxymethylfurfural and 5-Sulfooxymethylfurfural Increase Adenoma and Flat ACF Number in the Intestine of Min/+ Mice. Anticancer Res. 2009;29(6):1921-6.
• 33. Li Y, Lu X. Investigation on the Origin of 5-HMF in Shengmaiyin Decoction by RP-HPLC Method. J Zhejiang Univ Sci B. 2005;6(10):1015-21.
• 34. Michail K, Matzi V, Maier A, Herwig R, Greilberger J, Juan H, Kunert O, Wintersteiger R. Hydroxymethylfurfural: an Enemy or a Friendly Xenobiotic? A Bioanalytical Approach. Anal Bioanal Chem. 2007;387(8):2801-14.
• 35. Zhao L, Chen J, Su J, Li L, Hu S, Li B, Zhang X, Xu Z, Chen T. In vitro Antioxidant and Antiproliferative Activities of 5-hydroxymethylfurfural. J Agric Food Chem. 2013;61(44):10604-11.
• 36. Cao G, Cai H, Cai B, Tu S. Effect of 5-hydroxymethylfurfural Derived from Processed Cornus Officinalis on the Prevention of High Glucose-induced Oxidative Stres in Human Umbilical Vein Endothelial Cells and Its Mechanism. Food Chem. 2013;140(1-2):273-9.
• 37. Liu A, Zhao X, Li H, Liu Z, Liu B, Mao X Guo L, Bi K, Jia Y. 5-Hydroxymethylfurfural, an Antioxidant Agent from Alpinia Oxyphylla Miq. İmproves Cognitive Impairment in A𝛽 1–42 Mouse Model of Alzheimer’s Disease. Int Immunopharmacol. 2014;23(2):719-25.
• 38. Li MM, Wu LY, Zhao T, Xiong L, Huang X, Liu ZH Fan XL, Xiao CR, Gao Y, Ma YB, Chen JJ, Zhu LL, Fan M. The Protective Role of 5-HMF Against Hypoxic Injury. Cell Stress Chaperones 2011;16(3):267-73.
• 39. Yamada P, Nemoto M, Shigemori H, Yokota S, Isoda H. Isolationof 5-(hydroxymethyl) Furfural from Lycium Chinense and its Inhibitory Effect on the Chemical Mediator Release by Basophilic Cells. Planta Med. 2011;77(5):434-40.
• 40. Alizadeh M, Khodaei H, Mesgari Abbasi M, Saleh-Ghadimi S. Assessing the Effect of 5-hydroxymethylfurfural on Selected Components of Immune Responses in Mice Immunised with Ovalbumin. J Sci Food Agric. 2017;97(12):3979-84.
• 41. JECFA, Joint of FAO/WHO Food Standards Ppogramme Codex Committee on Sugars Seventh Session London, United Kingdom, 9-11 February 2000. www.fao.org/input/download/standards/310/cxs_012e.pdf (accessed January 11, 2018).
• 42. TFC. Turkish Food Codex, Meyve Suyu ve Benzeri Ürünler Tebliği, Tebliğ No: 2014/34. http://www.resmigazete.gov.tr/eskiler/2014/08 /20140806-17.htm. (accessed January 18, 2018).
• 43. Kjellstrand P, Martinson E, Wieslander A, Kjellstrand K, Jeppsson E, Svensson E, Järkelid L, Linden T, Olsson LF. Degradation in Peritoneal Dialysis Fluids may be Avoided by Using Low pH and High Glucose Concentration. Perit Dial Int. 2001;21(4):338-44.
• 44. Ulbricht RJ, Northup SJ, Thomas JA. A Review of 5-hydroxymethylfurfural (HMF) in Parenteral Solutions. Fundam Appl Toxicol. 1984;4(5):843-53.
• 45. European Council Directive 2001/110/EC of 20.12.2001. European Pharmacopoeia 8.0, Council of Europe. European Directorate for the Quality of Medicines and Health Care. https://www.fsai.ie/uploadedFiles/Consol_Dir2001_110.pdf. (accessed April 7, 2018).