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Determination of Relative Response Factors of Cefazolin Impurities by Quantitative NMR

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Abstract

The relative response factors (RRFs) of ten cefazolin impurities were determined by quantitative nuclear magnetic resonance (qNMR) and high-performance liquid chromatography (HPLC) equipped with an ultraviolet (UV) detector. The purities of these ten cefazolin impurities were successfully measured by qNMR for the purpose of RRFs determination by HPLC. The RRF values and their uncertainties determined by the two approaches are comparable. While the qNMR approach is effective and makes it easier to determine the RRFs for impurities, it also has the advantage of allowing the universal detection of protons without the limitations of common mass detectors. The use of qNMR provides a reliable and universal method for the RRF determination of impurities.

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References

  1. Görög S. The importance and the challenges of impurity profiling in modern pharmaceutical analysis. Trends Anal Chem. 2006;25(8):755–7.

    Article  Google Scholar 

  2. Jain D, Basniwal PK. Forced degradation and impurity profiling: recent trends in analytical perspectives. J Pharm Biomed Anal. 2013;86:11–35.

    Article  CAS  PubMed  Google Scholar 

  3. Narayanam M, Handa T, Sharma P, Jhajra S, Muthe PK, Dappili PK, et al. Critical practical aspects in the application of liquid chromatography–mass spectrometric studies for the characterization of impurities and degradation products. J Pharm Biomed Anal. 2014;87:191–217.

    Article  CAS  PubMed  Google Scholar 

  4. Maggio RM, Calvo NL, Vignaduzzo SE, Kaufman TS. Pharmaceutical impurities and degradation products: uses and applications of NMR techniques. J Pharm Biomed Anal. 2014;101:102–22.

    Article  CAS  PubMed  Google Scholar 

  5. USP. Cefazolin sodium. In: United States Pharmacopeia-National Formulary, USP35-NF 30. Rockville: Rand McNally; 2012. p. 2533–5.

  6. The State Pharmacopoeia Commission of PR China. Cefazolin sodium. In: Pharmacopoeia of the People’s Republic of China Edition 2010. Beijing: China Medical Science Press; 2010, p. 206–7.

  7. The British Pharmacopoeia Commission. Cefazolin sodium. In: British Pharmacopoeia 2013. London: Stationery Office; 2013. p. 1–7.

  8. The European Pharmacopoeia Commission. Cefazolin sodium. In: European Pharmacopoeia 8.0. Strasbourg: Council of Europe; 2014. p. 1794–6.

  9. The Society of Japanese Pharmacopoeia. Cefazolin sodium. In: Japanese Pharmacopoeia 15th. Tokyo: Yakuji Nippo, Ltd.; 2006. p. 426–8.

  10. Indian Pharmacopoeia Commission. Cefazolin sodium. In: Indian Pharmacopoeia 2010. Ghaziabad: Indian Pharmacopoeia Commission; 2010. p. 1005–6.

  11. Chávez-Servı́n JL, Castellote AI, López-Sabater MC. Analysis of mono-and disaccharides in milk-based formulae by high-performance liquid chromatography with refractive index detection. J Chromatogr A. 2004;1043:211–5.

    Article  PubMed  Google Scholar 

  12. Fang LL, Wan M, Pennacchio M, Pan JM. Evaluation of evaporative light-scattering detector for combinatorial library quantitation by reversed phase HPLC. J Comb Chem. 2000;2:254–7.

    Article  CAS  PubMed  Google Scholar 

  13. Nussbaum MA, Baertschi SW, Jansen PJ. Determination of relative UV response factors for HPLC by use of a chemiluminescent nitrogen-specific detector. J Pharm Biomed Anal. 2002;27:983–93.

    Article  CAS  PubMed  Google Scholar 

  14. Sun P, Wang X, Alquier L, Maryanoff CA. Determination of relative response factors of impurities in paclitaxel with high performance liquid chromatography equipped with ultraviolet and charged aerosol detectors. J Chromatogr A. 2008;1177:87–91.

    Article  CAS  PubMed  Google Scholar 

  15. Chakravarthy VK, Babu GK, Dasu RL, Prathyusha P, Kiran GA. The role of relative response factor in related substances method development by high preformance liquid chromatography (HPLC). Rasayan J. 2011;4(4):919–43.

    CAS  Google Scholar 

  16. World Health Organization. General guidelines for the establishment, maintenance and distribution of chemical reference substance. In: WHO Technical Report Series, No.885, Part A. Geneva; 1999. p. 5.

  17. The Directorate for the Quality of Medicines of the Council of Europe. Establishment of reference standards. In: European Pharmacopoeia, fifth ed., Supplement 5.6, General texts 5.12.4. Strasbourg; 2007.

  18. World Health Organization. Evaluation of chemical reference substance. In: International Pharmacopoeia. Geneva; 2003. p. 332–3.

  19. World Health Organization. General guidelines for the establishment, maintenance and distribution of chemical reference substances. In: WHO Technical Report Series, No.943, Annex 3. Geneva; 2006. p. 59–82.

  20. Holzgrabe U. Quantitative NMR, spectroscopy in pharmaceutical applications. Prog Nucl Magn Reson Spectrosc. 2010;57:229–40.

    Article  CAS  PubMed  Google Scholar 

  21. Pauli GF, Chen SN, Simmler C, Lankin DC, Gödecke T, Jaki BU, et al. Importance of purity evaluation and the potential of quantitative 1H NMR as a purity assay: miniperspective. J Med Chem. 2014;57:9220–931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu SY, Hu CQ. A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods. Anal Chim Acta. 2007;602:114–21.

    Article  CAS  PubMed  Google Scholar 

  23. National Institute of Metrology. Evaluation and expression of uncertainty in measurement. In: State Bureau of Quality Technical Supervision (ed). R.P.China; 1999. p. 2–16.

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Correspondence to Changqin Hu.

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Liu, S., Yao, S., Zhang, H. et al. Determination of Relative Response Factors of Cefazolin Impurities by Quantitative NMR. AAPS PharmSciTech 18, 1895–1900 (2017). https://doi.org/10.1208/s12249-016-0654-4

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  • DOI: https://doi.org/10.1208/s12249-016-0654-4

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