Skip to main content

Simultaneous Determination of Metformin Hydrochloride, Cyanoguanidine and Melamine in Tablets by Mixed-Mode HILIC

Abstract

A simple and specific hydrophilic interaction liquid chromatography (HILIC) procedure for the quantification of metformin hydrochloride (MFH) and its impurities in bulk pharmaceuticals and finished dosage forms has been developed. The method is based on hydrophilic interaction of the analytes with silica. The influence of the weaker solvent, acetonitrile, pH and the nature and ionic strength of the buffer was studied. Linearity range and percent recoveries for MFH were 100–400 μg mL−1 and 100.62%, respectively. Good validation data were obtained for all compounds. The method separates impurities cyanoguanidine (CGD), melamine (MLN) and other degradation products with a run time of less than 13 min. Degradation studies involved thermal stress, hydrolysis at various pHs and chemical and photolytic oxidation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. 1.

    USP 29 NF 24, United States Pharmacopoeia (2005) United States Pharmacopeial Convention, Inc., Rockville

  2. 2.

    James Reynolds EF, Part I, Martindale, The Extra Pharmacopoeia (1996) 31st edn. Royal Pharmaceutical Society of Great Britain, London

  3. 3.

    BP’ 2005, British Pharmacopoeia (2005) The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA), vol I–II

  4. 4.

    Arayne MS, Sultana N, Zuberi MH (2006) Pak J Pharm Sci 19:231–235

    CAS  Google Scholar 

  5. 5.

    Madhira BS, Vaibhav DM, Dimal AS, Kashyap KB, Rajendra SM, Madhira G, Binita JP (2005) J AOAC Int 88:1167–1172

    Google Scholar 

  6. 6.

    Kolte BL, Raut BB, Deo AA, Bagool MA, Shinde DB (2004) J Chromatogr Sci 42:27–31

    CAS  Google Scholar 

  7. 7.

    Ceren Y, Nuran Ö (2005) Anal Chim Acta 549:88–95

    Article  Google Scholar 

  8. 8.

    Kolte BL, Raut BB, Deo AA, Bagool MA, Shinde DB (2004) J Chromatogr Sci 42:70–73

    CAS  Google Scholar 

  9. 9.

    Vasudevan M, Ravi J, Ravisankar S, Suresh B (2001) J Pharm Biomed Anal 25:77–84

    Article  CAS  Google Scholar 

  10. 10.

    Ghassempour A, Ahmadi M, Ebrahimi SN, Aboul-Enein HY (2006) Chromatographia 64:101–104

    Article  CAS  Google Scholar 

  11. 11.

    Kolte BL, Raut BB, Deo AA, Bagool MA, Shinde DB (2006) Encyclopedia of Chromatography, Taylor & Francis, London

  12. 12.

    El-Khateeb SZ, Assaad HN, El-Bardicy MG, Ahmad AS (1998) Anal Chim Acta 208:321–324

    Article  Google Scholar 

  13. 13.

    Habib IHI, Kamel MS (2003) Talanta 60:185–190

    Article  CAS  Google Scholar 

  14. 14.

    Saad SMH, Wagiha HM, Mohamed AFE, Abdel Hammeed MO (1999) Anal Chim Acta 378:299–311

    Article  Google Scholar 

  15. 15.

    Ashour S, Kabbani R (2003) Anal Lett 36:361–370

    Article  CAS  Google Scholar 

  16. 16.

    El-bardicy MG, El-khateeb SZ, Abdelkader SA, Hoda NA (1989) Spectrosc Lett 22:1173–1181

    Article  CAS  Google Scholar 

  17. 17.

    Wang LR, Huang MZ, Zhu SH (2005) Zhejiang Da Xue Xue Bao Yi Xue Ban 34:368–371

    CAS  Google Scholar 

  18. 18.

    Victor D, Andrei M, Florin A (2005) J Liq Chromatogr Relat Technol 28:81–95

    Article  Google Scholar 

  19. 19.

    ICH Harmonized Tripartite Guideline, International Conference on Harmonization on Technical Requirements for Registration of Pharmaceuticals for Human Use, Q2A, Text on Validation of Analytical Procedures, Step 4 of the ICH process (1994) and Q2B, Validation of Analytical Procedures: Methodology, Step 4 of the ICH process (1996) ICH Steering Committee

  20. 20.

    Alpert AJ (1990) J Chromatogr 499:177–196

    Article  CAS  Google Scholar 

  21. 21.

    Naidong W (2003) J Chromatogr B 796:209–224

    Article  CAS  Google Scholar 

  22. 22.

    Neue UD, Grumbach ES, Mazzeo JR, Tran K, Wagrowski-Diehl DM (2003) In: Wilson ID (ed) Bioanalytical separations, handbook of analytical separations, Elsevier Science B. V., New York, pp 185–214

    Google Scholar 

  23. 23.

    Neue UD, Pheobe CH, Tran K, Cheng YF, Lu Z (2001) J Chromatogr A 925:49–67

    Article  CAS  Google Scholar 

  24. 24.

    Ali MS, Ghori M, Rafiuddin S, Khatri AR (2007) J Pharm Biomed Anal 43:158–167

    Article  CAS  Google Scholar 

  25. 25.

    Van de Merbel NC, Wilkens G, Fowles S, Oosterhuis B, Jonkman JHG (1998) Chromatographia 47:542–546

    Article  Google Scholar 

  26. 26.

    Hirt RC, Schmitt RG (1958) Spectrochim Acta 12:127–138

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Authors wish to thank Mr. Anwar Saeed, Mr. Mahmoud Yusuf Jamjoom and Mr. Noor Sheriff for encouraging this work and providing required support in accomplishing the proposed HILIC method.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mohammed Shahid Ali.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ali, M.S., Rafiuddin, S., Ghori, M. et al. Simultaneous Determination of Metformin Hydrochloride, Cyanoguanidine and Melamine in Tablets by Mixed-Mode HILIC. Chroma 67, 517–525 (2008). https://doi.org/10.1365/s10337-008-0542-5

Download citation

Keywords

  • Column liquid chromatography
  • HILIC
  • Metformin hydrochloride
  • Melamine
  • Cyanoguanidine
  • Degradation studies