کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
11006431 1503030 2018 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mimicking DNA alkylation: Removing genotoxin impurities from API streams with a solvent stable polybenzimidazole-adenine polymer
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Mimicking DNA alkylation: Removing genotoxin impurities from API streams with a solvent stable polybenzimidazole-adenine polymer
چکیده انگلیسی
This study reports the application of a novel polybenzimidazole (PBI) polymer modified with an alkylated DNA base - adenine - as an effective scavenger for several families of DNA alkylating agents. This new material addresses an important issue in active pharmaceutical ingredients (APIs) manufacture, the removal of genotoxic impurities (GTIs) to strictly low regulated limits. Instead of targeting individual GTIs removal, PBI-adenine scavenger mimics the concept of DNA-GTI adduct formation that takes place in vivo, but in this case, in an organic solvent matrix where APIs are chemically synthesized. Removal of eleven GTIs from five different chemical families is assessed with >80% removal. Slow binding kinetics for some GTIs at room temperature was identified as one of the limitations of the PBI-adenine polymer. API purification is addressed and an efficient process is presented for two APIs studied, mometasone furoate and betamethasone acetate, affording high impurity removals (>96%) and high API recovery with low API loss (3.5%) for these case studies. The possible application of this straightforward strategy in API post-reaction stream purification, is able to attain GTI imposed limits as low as 0.6 mg GTI/g API respecting the Threshold of Toxicological Concern (TTC) value.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Reactive and Functional Polymers - Volume 131, October 2018, Pages 258-265
نویسندگان
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