- Enrichment of Relevant Oxidative Degradation Products in Pharmaceuticals With Targeted Chemoselective Oxidation
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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.
- Nanda, Kausik K.,Mozziconacci, Olivier,Small, James,Allain, Leonardo R.,Helmy, Roy,Wuelfing, W. Peter
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p. 1466 - 1475
(2019/01/22)
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- Benzothiophenes, formulations containing same, and methods
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This invention provides novel benzothiophene compounds.
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- Benzothiophenes, formulations containing same, and methods
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This invention provides pharmaceutical benzothiophene compounds of the formula wherein R1is hydrogen, hydroxy, C1-C4alkoxy, wherein Ar is optionally substituted phenyl, or -SO2(C4-C6straight chain alkyl); R2is R1, Cl or F; and R3and R4are, independently, C1-C4alkyl or combine to form a C4-C6polymethylene or, together with the nitrogen to which they are attached form morpholine, X is -CH2, -CHOH2-, -O-, or or a pharmaceutically acceptable salt or solvate thereof.
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