Share This Article:

A Validated Stability-Indicating LC Method for Fluocinonide in the Presence of Degradation Products, Its Process-Related Impurities and Identification of Degradation Products

Abstract Full-Text HTML Download Download as PDF (Size:953KB) PP. 113-126
DOI: 10.4236/ajac.2010.13015    6,560 Downloads   13,222 Views   Citations

ABSTRACT

The objective of the current study was to develop a validated, specific and stability-indicating reverse phase liquid chromatographic method for the quantitative determination of fluocinonide and its related substances. The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities. The drug was subjected to stress condi- tions of hydrolysis (acid and base), oxidation, photolysis and thermal degradation per International Confer- ence on Harmonization (ICH) prescribed stress conditions to show the stability- indicating power of the method. Significant degradation was observed during acid, base hydrolysis, and peroxide degradation. The major degradants were identified by LC-MS, FTIR and 1H/13C NMR spectral analysis. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degra- dation studies. In the developed HPLC method, the resolution between fluocinonide and its process-related impurities, (namely imp-1, imp-2, imp-3, imp-4, imp-5, imp-6, imp-7 and imp-8) and its degradation products was found to be greater than 2.0.The chromatographic separation was achieved on a C18, 250 mm × 4.6 mm, 5 µm column. The LC method employed a linear gradient elution and the detection wavelength was set at 240 nm. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.3%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

P. Srinivasu, D. SubbaRao, R. Vegesna and K. Babu, "A Validated Stability-Indicating LC Method for Fluocinonide in the Presence of Degradation Products, Its Process-Related Impurities and Identification of Degradation Products," American Journal of Analytical Chemistry, Vol. 1 No. 3, 2010, pp. 113-126. doi: 10.4236/ajac.2010.13015.

References

[1] R. D. Zenoble and R. J. Kemppainen, “Adrenocortical Suppression by Topically Applied Corticosteroids in Healthy Dogs,” Journal of American Veterinary Medical Association, Vol. 191, No. 6, 1987, pp. 685-688.
[2] Fluocinonide, United States Pharmacopeia USP32 NF 27, 2009, pp. 2401-2403.
[3] E. Shek, J. Bragonje, E. J. Benjamin, M. J. Sutherland and J. A. P. Gluck, “A Stability Indicating High-Performance Liquid Chromatography Determination of Triple Corticoid Integrated System in a Cream,” International Journal of Pharmaceutics, Vol. 11, No. 3, 1982, pp. 257-269.
[4] E. Bailey and P. N. Brittain, “The Quantitative Determination of Fluocinolone Acetonide and Acetonide Acetate in Formulated Products by High Pressure Liquid Chromatography,” Journal of Pharmacy and Pharmacology, Vol. 24, No. 6, 1972, pp. 425-428.
[5] W. C. Landgraf and E. C. Jennings, “Steroid Determination from Complex Mixtures by High Pressure Chroma- tographic Techniques,” Journal of Pharmaceutical Sciences, Vol. 62, No. 2, 1973, pp. 278-281.
[6] F. Biley, A. Holbrook and R. J. Miller, “The Determina- tion of Fluocinolone Acetonide in Formulated Products,” Journal of Pharmacy and Pharmacology, Vol. 18, 1966, pp. 12S-16S.
[7] M. Bakshi and S. Singh, “Development of Validated Stability Indicating Assay Methods—Critical Review,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 28, No. 6, 2002, pp. 1011-1040.
[8] P. Srinivasu, D. V. Subbarao, R. V. K. Vegesna, K. S. Babu, “A Validated Stability Indicating LC Method for Acetazolamide in the Presence of Degradation Products and Its Process Related Impurities,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 52, No. 1, 2010, pp. 142-148.
[9] D. V. Subbarao, P. Radhakrishnanand and V. Himabindu, “Stress Degradation Studies on Tadalafil and Development of a Validated Stability Indicating LC Assay for Bulk Drug and Pharmaceutical Dosage Form,” Chromatographia, Vol. 67, No. 1-2, 2008, pp. 183-188.
[10] D. V. Subbarao, P. Radhakrishnanand, M. V. Suryanarayana and V. Himabindu, “A Stability Indicating LC Method for Candesartan Cilexetil,” Chromatographia, Vol. 66, No. 7-8, 2007, pp. 499-507.
[11] A. Madhavi, D. V. Subbarao, P. Srinivasu and A. Naidu, “Development and Validation of a New Analytical Method for the Determination of Related Components and Assay of Ranolazine in Bulk Drug and Pharmaceutical Dosage Forms by LC,” Chromatographia, Vol. 70, No. 1-2, 2009, pp. 333-338.
[12] A. Madhavi, A. Naidu, D. V. Subbarao and P. Srinivasu, “Development and Validation of a New LC Method for the Analysis of Determination of Brimonidine Tartrate and Related Components,” Chromatographia, Vol. 69, No. 11-12, 2009, pp. 1413-1419.
[13] J. T. Carstensen and C. T. Rhodes, “Drug Stability Principles and Practices,” 3rd Edition, Marcel Dekker, New York, 2000.
[14] U.S. Food and Drug Administration, “ICH Guidelines on Validation of Analytical Procedures: Text and Methodology Q2 (R1),” Federal Register, FDA, Silver Spring, 2005.
[15] International Federation of Pharmaceutical Manufactures & Associations, “ICH Stability Testing of New Drug Substances and Products Q1A (R2),” International Conference on Harmonization, Geneva, 2003.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.