A Novel Validated Stability Indicative UP-LC Method for Etravirine for the Determination of Process Related and Degradation Impurities

DOI: 10.4236/ajac.2012.312111   PDF   HTML     3,035 Downloads   5,180 Views   Citations

Abstract

A novel stability indicating reverse phase ultra performance liquid chromatographic (UP-LC) method has been developed for Etravirine along with eight impurities (imp-1, imp-2, imp-3, imp-4, imp-5, imp-6, imp-7 and imp-8) and validated as per ICH recommendations. Stress degradation conditions were established for Etravirine by subjecting it to stress conditions of acid, base, oxidation, humidity, thermal and photolysis. Significant degradation is observed in base stress condition and the major degradant (RRT at about 0.94) is identified by LC-MS and spectral analysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.0%. Efficient chromatographic separation was achieved on a Shimpack ODS-II stationary phase with a gradient mobile phase combination. Quantification was carried at 303 nm at a flow rate of 0.6 mL?min–1. The resolution between Etravirine and eight potential impurities is found to be greater than 2.0. Regression analysis shows as r value (correlation coefficient) of greater than 0.999 for Etravirine and eight potential impurities. This method is capable to detect the impurities of Etravirine at a level of 0.003% with respect to test concentration of 1.0 mg·mL–1.

Share and Cite:

M. Chilukuri, K. Reddy, P. Narayanareddy and M. Venkataramana, "A Novel Validated Stability Indicative UP-LC Method for Etravirine for the Determination of Process Related and Degradation Impurities," American Journal of Analytical Chemistry, Vol. 3 No. 12, 2012, pp. 840-848. doi: 10.4236/ajac.2012.312111.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] M. Rowley, “The Discovery of Raltegravir, an Integrals Inhibitor for the Treatment of HIV Infection,” Progress in Medicinal Chemistry, Vol. 46, No. 5, 2008, pp. 1-28. doi:10.1016/S0079-6468(07)00001-X
[2] Y. Van Herrewege, G. Vanham, J. Michiels, K. Fransen, L. Kestens, K. Andries, P. Janssen and P. Lewi, “A series of Diaryltriazines and Diarylpyrimidines Are Highly Potent Nonnucleoside Reverse Transcriptase Inhibitors with Possible Applications as Microbicides,” Antimicrobial Agents and Chemotherapy, Vol. 48, No. 10, 2004, pp. 3684-3689. doi:10.1128/AAC.48.10.3684-3689.2004
[3] C. Mordant, B. Schmitt, E. Pasquier, C. Demestre, L. Queguiner, C. Masungi, A. Peeters, L. Smeulders, E. Bettens, K. Hertogs, J. Heeres, P. Lewi and J. Guillemont, “Synthesis of Novel Diarylpyrimidine Analogues of TMC278 and Their Antiviral Activity Against HIV-1 Wildtype and Mutant Strains,” European Journal of Medicinal Chemistry, Vol. 42, No. 5, 2007, pp. 567-579. doi:10.1016/j.ejmech.2006.11.014
[4] F. Goebel, A. Yakovlev, A. L. Pozniak, E. Vinogradova, G. Boogaerts, R. Hoetelmans, M. P. Béthune, M. Peeters and B. Woodfall, “Short-Term Antiviral Activity of TMC278—A Novel NNRTI—In Treatment-Naive HIV- 1-Infected Subjects”, AIDS, Vol. 20, No. 13, 2006, pp. 1721-1726. doi:10.1097/01.aids.0000242818.65215.bd
[5] C. Fang, J. D. Bauman, K. Das, A. Remorino, E. Arnold and R. M. Hochstrasser, “Two-Dimensional Infrared Spectra Reveal Relaxation of the Nonnucleoside Inhibitor TMC278 Complexed with HIV-1 Reverse Transcriptase,” Proceedings of the National Academy of Sciences, USA, Vol. 105, No. 5, 2007, pp. 1472-1477. doi:10.1073/pnas.0709320104
[6] A. D’Avolio, M. Simiele, M. Siccardi, L. Baietto, M. Sciandra, V. Oddone, et al., “A HPLC-MS Method for the Simultaneous Quantification of Fourteen Antiretroviral Agents in Peripheral Blood Mono-nuclear Cell of HIV Infected Patients Optimized Using Medium Corpuscular Volume Evaluation,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 25, No. 4, 2011, pp. 779-788.
[7] A ahamed, G. Krishnamurthy, H. S. Bhojya naik and S. Ramesha, “Development and Validation of Stability In-dicating Ultra Performance Liquid Chromatographic Method for Etravirine,” International Journal of Phar- macy and Pharmaceutical Sciences, Vol. 4, No. 1, 2011, pp. 255-261.
[8] L. Else, V. Watson, J. Tjia, A. Hughes, M. Siccardi, S. Khoo, et al., “Validation Of A Rapid And Sensitive High-Performance Liquid Chromatography—Tandem Mass Spectrometry (HPLC–MS/MS) Assay For The Simultaneous Determination Of Existing And New Antiretroviral Compounds,” Journal of Chromatography B, Vol. 878, No. 19, 2010, pp. 1455-1465. doi:10.1016/j.jchromb.2010.03.036
[9] International Conference on Harmonisation, “Validation of Analytical Procedures: Text and Methodology,” Q2 (R1), 2005.
[10] International Conference on Harmonisation, “Stability Testing of New Drug Substances and Products Q1A (R2),” International Federation of Pharmaceutical Manufaturers Associations, Geneva, 2003.
[11] International Conference on Harmonisation, “Photo Stability Testing of New Drug Substances and Products,” Q1B, IFPMA, Geneva, 1996.
[12] S. Singh and M. Bakshi, “Guidance on Conduct of Stress Tests to Determine Inherent Stability of Drugs,” Pharmaceutical Technology Online, Vol. 24, 2000, pp. 1-14.
[13] International Conference on Harmonisation, “Guidelines on Validation of Analytical Procedures Definitions and Terminology,” Tripartite Guideline, EMEA, 1994.
[14] J. T. Carstensen, “Drug Stability Principles and Practices,” 2nd Edition, Marcel Decker, New York, 1995, pp. 3-4.
[15] 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. doi:10.1016/S0731-7085(02)00047-X
[16] The United States Pharmacopeial Convention, “Validation of Compendial Methods,” The United States Pharmacopeia, 32nd Edition, USP32, 2008.
[17] J. T Carstensen and C. T. Rhodes, “Drug Stability Principles and Practices,” 3rd Edition, Marcel Dekker, New York, 2000.

  
comments powered by Disqus

Copyright © 2020 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.