Cargando…

Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII

The novel reverse phase-high performance liquid chromatography (RP-HPLC), stability indicating method was developed for determination of linagliptin (LGP) and its related substances in linagliptin and metformin HCl (MET HCl) tablets by implementing design of experiment to understand the critical met...

Descripción completa

Detalles Bibliográficos
Autores principales: Jadhav, Sushant B., Reddy, P. Sunil, Narayanan, Kalyanaraman L., Bhosale, Popatrao N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620513/
https://www.ncbi.nlm.nih.gov/pubmed/28653975
http://dx.doi.org/10.3390/scipharm85030025
_version_ 1783267600335110144
author Jadhav, Sushant B.
Reddy, P. Sunil
Narayanan, Kalyanaraman L.
Bhosale, Popatrao N.
author_facet Jadhav, Sushant B.
Reddy, P. Sunil
Narayanan, Kalyanaraman L.
Bhosale, Popatrao N.
author_sort Jadhav, Sushant B.
collection PubMed
description The novel reverse phase-high performance liquid chromatography (RP-HPLC), stability indicating method was developed for determination of linagliptin (LGP) and its related substances in linagliptin and metformin HCl (MET HCl) tablets by implementing design of experiment to understand the critical method parameters and their relation with critical method attributes; to ensure robustness of the method. The separation of nine specified impurities was achieved with a Zorbax SB-Aq 250 × 4.6 mm, 5 µm column, using gradient elution and a detector wavelength of 225 nm, and validated in accordance with International Conference on Harmonization (ICH) guidelines and found to be accurate, precise, reproducible, robust, and specific. The drug was found to be degrading extensively in heat, humidity, basic, and oxidation conditions and was forming degradation products during stability studies. After slight modification in the buffer and the column, the same method was used for liquid chromatography–mass spectrometry (LC-MS) and ultra-performance liquid chromatography -time-of-flight/mass spectrometry UPLC-TOF/MS analysis, to identify m/z and fragmentation of maximum unspecified degradation products i.e., Impurity-VII (7), Impurity-VIII (8), and Impurity-IX (9) formed during stability studies. Based on the results, a degradation pathway for the drug has been proposed and synthesis of Impurity-VII (7) is also discussed to ensure an in-depth understanding of LGP and its related degradation products and optimum performance during the lifetime of the product.
format Online
Article
Text
id pubmed-5620513
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-56205132017-10-06 Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII Jadhav, Sushant B. Reddy, P. Sunil Narayanan, Kalyanaraman L. Bhosale, Popatrao N. Sci Pharm Article The novel reverse phase-high performance liquid chromatography (RP-HPLC), stability indicating method was developed for determination of linagliptin (LGP) and its related substances in linagliptin and metformin HCl (MET HCl) tablets by implementing design of experiment to understand the critical method parameters and their relation with critical method attributes; to ensure robustness of the method. The separation of nine specified impurities was achieved with a Zorbax SB-Aq 250 × 4.6 mm, 5 µm column, using gradient elution and a detector wavelength of 225 nm, and validated in accordance with International Conference on Harmonization (ICH) guidelines and found to be accurate, precise, reproducible, robust, and specific. The drug was found to be degrading extensively in heat, humidity, basic, and oxidation conditions and was forming degradation products during stability studies. After slight modification in the buffer and the column, the same method was used for liquid chromatography–mass spectrometry (LC-MS) and ultra-performance liquid chromatography -time-of-flight/mass spectrometry UPLC-TOF/MS analysis, to identify m/z and fragmentation of maximum unspecified degradation products i.e., Impurity-VII (7), Impurity-VIII (8), and Impurity-IX (9) formed during stability studies. Based on the results, a degradation pathway for the drug has been proposed and synthesis of Impurity-VII (7) is also discussed to ensure an in-depth understanding of LGP and its related degradation products and optimum performance during the lifetime of the product. MDPI 2017-06-27 2017 /pmc/articles/PMC5620513/ /pubmed/28653975 http://dx.doi.org/10.3390/scipharm85030025 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jadhav, Sushant B.
Reddy, P. Sunil
Narayanan, Kalyanaraman L.
Bhosale, Popatrao N.
Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title_full Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title_fullStr Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title_full_unstemmed Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title_short Development of RP-HPLC, Stability Indicating Method for Degradation Products of Linagliptin in Presence of Metformin HCl by Applying 2 Level Factorial Design; and Identification of Impurity-VII, VIII and IX and Synthesis of Impurity-VII
title_sort development of rp-hplc, stability indicating method for degradation products of linagliptin in presence of metformin hcl by applying 2 level factorial design; and identification of impurity-vii, viii and ix and synthesis of impurity-vii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620513/
https://www.ncbi.nlm.nih.gov/pubmed/28653975
http://dx.doi.org/10.3390/scipharm85030025
work_keys_str_mv AT jadhavsushantb developmentofrphplcstabilityindicatingmethodfordegradationproductsoflinagliptininpresenceofmetforminhclbyapplying2levelfactorialdesignandidentificationofimpurityviiviiiandixandsynthesisofimpurityvii
AT reddypsunil developmentofrphplcstabilityindicatingmethodfordegradationproductsoflinagliptininpresenceofmetforminhclbyapplying2levelfactorialdesignandidentificationofimpurityviiviiiandixandsynthesisofimpurityvii
AT narayanankalyanaramanl developmentofrphplcstabilityindicatingmethodfordegradationproductsoflinagliptininpresenceofmetforminhclbyapplying2levelfactorialdesignandidentificationofimpurityviiviiiandixandsynthesisofimpurityvii
AT bhosalepopatraon developmentofrphplcstabilityindicatingmethodfordegradationproductsoflinagliptininpresenceofmetforminhclbyapplying2levelfactorialdesignandidentificationofimpurityviiviiiandixandsynthesisofimpurityvii