Analytical Method Development and Validation for the Determination of Ethylene Glycol and Diethylene Glycol in Herbal Cough Syrup by Gas Chromatography

Ethylene Glycol (EG) and Diethylene Glycol (DEG) are potential contaminants in liquid oral formulations, posing severe toxicological risks. Regulatory agencies mandate stringent controls on their permissible limits. This study outlines the analytical method verification of a gas chromatography (GC) procedure for the quantitative determination of EG and DEG in a polyherbal cough syrup. The method employs a DB-624 capillary column and flame ionization detection (FID), using ethanol as the diluent. System suitability, precision, resolution, and tailing factor criteria were established and verified. The method was confirmed to be accurate, precise, and suitable for routine use in quality control.

Ethylene Glycol, Diethylene Glycol, Gas Chromatography

1. ICH Q2(R1). (2005). Validation of Analytical Procedures: Text and Methodology. International Council for Harmonisation. [Google Scholar] [Crossref]

2. USP <621> Chromatography. United States Pharmacopeia and National Formulary (USP-NF), USP 43–NF 38. [Google Scholar] [Crossref]

3. FDA. (2015). Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics. U.S. Department of Health and Human Services. [Google Scholar] [Crossref]

4. European Medicines Agency. (2014). Guideline on Bioanalytical Method Validation. [Google Scholar] [Crossref]

5. Snyder, L. R., Kirkland, J. J., & Dolan, J. W. (2010). Introduction to Modern Liquid Chromatography. John Wiley & Sons. [Google Scholar] [Crossref]

6. Dong, M. W. (2006). Modern HPLC for Practicing Scientists. Wiley-Interscience. [Google Scholar] [Crossref]

7. Kazakevich, Y. V., & Lobrutto, R. (2007). HPLC for Pharmaceutical Scientists. Wiley-Interscience. [Google Scholar] [Crossref]

8. Swartz, M. E., & Krull, I. S. (2012). Analytical Method Development and Validation. CRC Press. [Google Scholar] [Crossref]

9. Chou, S. S., & MacCrehan, W. A. (1995). Determination of ethylene glycol and diethylene glycol in pharmaceuticals using capillary gas chromatography. Journal of Chromatography A, 707(2), 317–322. [Google Scholar] [Crossref]

10. EMEA. (2008). Diethylene Glycol in Contaminated Glycerin. European Medicines Agency report. [Google Scholar] [Crossref]

11. Krishnaiah, Y. S. R., et al. (2013). Method development and validation for simultaneous determination of EG and DEG in cough syrup. Journal of Pharmaceutical and Biomedical Analysis, 85, 1–6. [Google Scholar] [Crossref]

12. Dharuman, J., & Sinha, P. K. (2017). GC-FID method for determination of glycol contaminants in pharmaceutical preparations. Asian Journal of Chemistry, 29(12), 2579–2582. [Google Scholar] [Crossref]

13. U.S. FDA. (2007). Public Health Advisory on DEG contamination in cough syrups. U.S. Food and Drug Administration. [Google Scholar] [Crossref]

14. Jiang, Y., et al. (2010). Determination of multiple components in herbal cough syrup using GC-MS. Phytochemical Analysis, 21(6), 574–579. [Google Scholar] [Crossref]

15. Mokhtari, V., et al. (2021). Herbal medicine quality control using chromatographic techniques.Evidence-Based Complementary and Alternative Medicine, 2021. [Google Scholar] [Crossref]

16. WHO. (2005). Quality Control Methods for Herbal Materials. World Health Organization. [Google Scholar] [Crossref]

17. EMA/HMPC. (2017). Guideline on quality of herbal medicinal products/traditional herbal medicinal products. [Google Scholar] [Crossref]

18. Patel, R. M., & Patel, A. A. (2015). Challenges in analysis of polyherbal formulations. Journal of Pharmacy Research, 9(9), 541–545. [Google Scholar] [Crossref]

19. Agency for Toxic Substances and Disease Registry (ATSDR). (2010). Toxicological Profile for Ethylene Glycol and Propylene Glycol. [Google Scholar] [Crossref]

20. Barceloux, D. G., et al. (1999). Ethylene glycol poisoning: Mechanisms and management.Journal of Toxicology: Clinical Toxicology, 37(5), 581–609. [Google Scholar] [Crossref]

21. Hantson, P., et al. (2000). Diethylene glycol poisoning: A case report. Human & Experimental Toxicology, 19(4), 231–234. [Google Scholar] [Crossref]

22. Chan, Y. C., et al. (2004). Detection of DEG in adulterated cough syrups. Journal of Forensic Sciences, 49(5), 1058–1061. [Google Scholar] [Crossref]

23. Samanidou, V. F., et al. (2004). Development and validation of an HPLC method for determination of preservatives and additives. Journal of Chromatographic Science, 42(6), 295–301. [Google Scholar] [Crossref]

24. Nogueira, J. A., et al. (2002). Validation of GC-MS methods for trace analysis in complex matrices. Talanta, 58(5), 1065–1072. [Google Scholar] [Crossref]

25. Rao, R. N., et al. (2006). RP-HPLC method validation for pharmaceutical compounds in complex matrices. Journal of Pharmaceutical and Biomedical Analysis, 40(3), 659–667. [Google Scholar] [Crossref]

26. Grob, R. L., & Barry, E. F. (2004). Modern Practice of Gas Chromatography. Wiley-Interscience. [Google Scholar] [Crossref]

27. Marriott, P. J., et al. (2001). Comprehensive two-dimensional gas chromatography. Journal of Chromatography A, 936(1–2), 1–22. [Google Scholar] [Crossref]

28. Dettmer-Wilde, K., & Engewald, W. (2014). Practical Gas Chromatography: A Comprehensive Reference. Springer. [Google Scholar] [Crossref]

29. WHO Alert (2022). Medical Product Alert N°6/2022: Contaminated Cough Syrups. Geneva: World Health Organization. [Google Scholar] [Crossref]

30. GACVS (Global Advisory Committee on Vaccine Safety). (2023). Safety of medicinal syrups and glycol contamination. [Google Scholar] [Crossref]

31. CDSCO (India). (2023). Regulatory Circular on DEG Contamination in Pharmaceuticals. [Google Scholar] [Crossref]

32. Health Canada. (2022). Advisory on DEG contamination in children's cough formulations. [Google Scholar] [Crossref]

33. Kumar, A., et al. (2015). Quality control of liquid oral formulations using chromatographic tools. Indian Journal of Pharmaceutical Sciences, 77(4), 475–481. [Google Scholar] [Crossref]

34. Raj, K. G., et al. (2019). Validation of analytical methods in herbal matrix using QbD approach.International Journal of Green Pharmacy, 13(3), 213–219. [Google Scholar] [Crossref]

35. Nema, R. K., & Kumar, A. (2008). Quality assessment of polyherbal syrups: An overview.Pharmacognosy Reviews, 2(4), 62–68. [Google Scholar] [Crossref]

36. Sharma, S., et al. (2020). Current status of herbal drug analysis and validation. Asian Journal of Pharmaceutical Analysis, 10(2), 102–110. [Google Scholar] [Crossref]

37. Satheeshkumar, N., et al. (2014). Challenges and strategies in herbal drug quality control.Journal of Natural Remedies, 14(2), 85–94. [Google Scholar] [Crossref]

38. Kaur, H., et al. (2021). Analytical method development for herbal APIs using chromatography.Journal of AOAC International, 104(1), 182–191. [Google Scholar] [Crossref]

39. Chawla, G., & Singh, S. (2009). Impurity profiling: A regulatory perspective. Pharmaceutical Technology Europe, 21(11), 40–48. [Google Scholar] [Crossref]

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