Enrichment of Relevant Oxidative Degradation Products in Pharmaceuticals With Targeted Chemoselective Oxidation
| Autor: | Roy Helmy, W. Peter Wuelfing, Kausik K. Nanda, Olivier Mozziconacci, James H. Small, Leonardo R. Allain |
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| Rok vydání: | 2019 |
| Předmět: |
Active ingredient
Oxidative degradation Chemistry Chemistry Pharmaceutical Drug Compounding Drug Storage Pharmaceutical Science Hydrogen Peroxide 02 engineering and technology Oxidants 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Degradation (geology) Drug product Indicators and Reagents Product (category theory) Biochemical engineering 0210 nano-technology Oxidation-Reduction Chromatography High Pressure Liquid |
| Zdroj: | Journal of Pharmaceutical Sciences. 108:1466-1475 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2018.10.059 |
| Popis: | The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource- and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H2O2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above. |
| Databáze: | OpenAIRE |
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