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Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations
PURPOSE: Isolation and identification of unknown impurities of recombinant insulin lispro (produced at IBA) formed during accelerated stability testing of pharmaceutical solutions. For comparative purposes also commercially available formulations of recombinant human insulin (Humulin S®; Lilly), rec...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956049/ https://www.ncbi.nlm.nih.gov/pubmed/29770892 http://dx.doi.org/10.1007/s11095-018-2426-1 |
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author | Zielińska, Joanna Stadnik, Jacek Bierczyńska-Krzysik, Anna Stadnik, Dorota |
author_facet | Zielińska, Joanna Stadnik, Jacek Bierczyńska-Krzysik, Anna Stadnik, Dorota |
author_sort | Zielińska, Joanna |
collection | PubMed |
description | PURPOSE: Isolation and identification of unknown impurities of recombinant insulin lispro (produced at IBA) formed during accelerated stability testing of pharmaceutical solutions. For comparative purposes also commercially available formulations of recombinant human insulin (Humulin S®; Lilly), recombinant insulin lispro (Humalog®; Lilly), recombinant insulin aspart (NovoRapid® Penfill®; Novo Nordisk), recombinant insulin detemir (Levemir®; Novo Nordisk) and recombinant insulin glargine (Lantus®; Sanofi-Aventis) were analyzed. METHODS: The impurities of insulin analogs were isolated by RP-HPLC and identified with peptide mass fingerprinting using MALDI-TOF/TOF mass spectrometry. RESULTS: The identified derivatives were N-terminally truncated insulin analog impurities of decreased molecular mass of 119, 147 and 377 Da related to the original protein. The modifications resulting in a mass decrease were detected at the N-terminus of B chains of insulin lispro, insulin aspart, human insulin, insulin glargine, insulin detemir in all tested formulations. To our knowledge it is the first time that these impurities are reported. CONCLUSIONS: The following derivatives formed by truncation of the B chain in insulin analogs were identified in pharmaceutical formulations: desPhe(B1)-N-formyl-Val(B2) derivative, desPhe(B1) derivative, pyroGlu(B4) derivative. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-018-2426-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5956049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-59560492018-05-18 Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations Zielińska, Joanna Stadnik, Jacek Bierczyńska-Krzysik, Anna Stadnik, Dorota Pharm Res Research Paper PURPOSE: Isolation and identification of unknown impurities of recombinant insulin lispro (produced at IBA) formed during accelerated stability testing of pharmaceutical solutions. For comparative purposes also commercially available formulations of recombinant human insulin (Humulin S®; Lilly), recombinant insulin lispro (Humalog®; Lilly), recombinant insulin aspart (NovoRapid® Penfill®; Novo Nordisk), recombinant insulin detemir (Levemir®; Novo Nordisk) and recombinant insulin glargine (Lantus®; Sanofi-Aventis) were analyzed. METHODS: The impurities of insulin analogs were isolated by RP-HPLC and identified with peptide mass fingerprinting using MALDI-TOF/TOF mass spectrometry. RESULTS: The identified derivatives were N-terminally truncated insulin analog impurities of decreased molecular mass of 119, 147 and 377 Da related to the original protein. The modifications resulting in a mass decrease were detected at the N-terminus of B chains of insulin lispro, insulin aspart, human insulin, insulin glargine, insulin detemir in all tested formulations. To our knowledge it is the first time that these impurities are reported. CONCLUSIONS: The following derivatives formed by truncation of the B chain in insulin analogs were identified in pharmaceutical formulations: desPhe(B1)-N-formyl-Val(B2) derivative, desPhe(B1) derivative, pyroGlu(B4) derivative. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-018-2426-1) contains supplementary material, which is available to authorized users. Springer US 2018-05-16 2018 /pmc/articles/PMC5956049/ /pubmed/29770892 http://dx.doi.org/10.1007/s11095-018-2426-1 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Paper Zielińska, Joanna Stadnik, Jacek Bierczyńska-Krzysik, Anna Stadnik, Dorota Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title | Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title_full | Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title_fullStr | Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title_full_unstemmed | Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title_short | Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations |
title_sort | identification of n-terminally truncated derivatives of insulin analogs formed in pharmaceutical formulations |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956049/ https://www.ncbi.nlm.nih.gov/pubmed/29770892 http://dx.doi.org/10.1007/s11095-018-2426-1 |
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