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Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS

A rapid, selective, and reliable LC-MS(n) method has been developed and validated for the isolation and structural characterization of the degradation product of darunavir (DRV). DRV, an HIV-1 protease inhibitor, was subjected to intrinsic oxidative stress conditions using 30% hydrogen peroxide and...

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Autores principales: Yamjala, Karthik, Atukuri, Jeevitha, Nagappan, Krishnaveni, Halekote Shivaraju, Nivedeetha, Subramania Nainar, Meyyanathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Austrian Journal of Pharmaceutical Sciences 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727738/
https://www.ncbi.nlm.nih.gov/pubmed/26839843
http://dx.doi.org/10.3797/scipharm.1505-10
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author Yamjala, Karthik
Atukuri, Jeevitha
Nagappan, Krishnaveni
Halekote Shivaraju, Nivedeetha
Subramania Nainar, Meyyanathan
author_facet Yamjala, Karthik
Atukuri, Jeevitha
Nagappan, Krishnaveni
Halekote Shivaraju, Nivedeetha
Subramania Nainar, Meyyanathan
author_sort Yamjala, Karthik
collection PubMed
description A rapid, selective, and reliable LC-MS(n) method has been developed and validated for the isolation and structural characterization of the degradation product of darunavir (DRV). DRV, an HIV-1 protease inhibitor, was subjected to intrinsic oxidative stress conditions using 30% hydrogen peroxide and the degradation profile was studied. The oxidative degradation of DRV resulted in one degradation product. The unknown degradation product was separated on a Hibar Purospher C(18) (250 mm × 4.6 mm; 5 µm) column by using 0.01 M ammonium formate (pH 3.0) and acetonitrile as mobile phase in the ratio of 50:50, v/v. The eluents were monitored at 263 nm using a UV detector. The isolated degradation product was characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability-indicating LC method was validated with respect to accuracy, precision, specificity/selectivity, and linearity. No prior reports were found in the literature about the oxidative degradation behavior of DRV.
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spelling pubmed-47277382016-02-02 Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS Yamjala, Karthik Atukuri, Jeevitha Nagappan, Krishnaveni Halekote Shivaraju, Nivedeetha Subramania Nainar, Meyyanathan Sci Pharm Research Article A rapid, selective, and reliable LC-MS(n) method has been developed and validated for the isolation and structural characterization of the degradation product of darunavir (DRV). DRV, an HIV-1 protease inhibitor, was subjected to intrinsic oxidative stress conditions using 30% hydrogen peroxide and the degradation profile was studied. The oxidative degradation of DRV resulted in one degradation product. The unknown degradation product was separated on a Hibar Purospher C(18) (250 mm × 4.6 mm; 5 µm) column by using 0.01 M ammonium formate (pH 3.0) and acetonitrile as mobile phase in the ratio of 50:50, v/v. The eluents were monitored at 263 nm using a UV detector. The isolated degradation product was characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability-indicating LC method was validated with respect to accuracy, precision, specificity/selectivity, and linearity. No prior reports were found in the literature about the oxidative degradation behavior of DRV. The Austrian Journal of Pharmaceutical Sciences 2015 2015-06-30 /pmc/articles/PMC4727738/ /pubmed/26839843 http://dx.doi.org/10.3797/scipharm.1505-10 Text en Copyright: © Yamjala et al. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yamjala, Karthik
Atukuri, Jeevitha
Nagappan, Krishnaveni
Halekote Shivaraju, Nivedeetha
Subramania Nainar, Meyyanathan
Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title_full Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title_fullStr Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title_full_unstemmed Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title_short Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS
title_sort characterization of the oxidative degradation product of darunavir by lc-ms/ms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727738/
https://www.ncbi.nlm.nih.gov/pubmed/26839843
http://dx.doi.org/10.3797/scipharm.1505-10
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