کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513652 | 1556498 | 2017 | 22 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of N-Acetyl-Tryptophan Degradation in Protein Therapeutic Formulations
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کلمات کلیدی
AAPHNFKOIAPICNATHSATrpmAb2,2′-azobis(2-amidinopropane) dihydrochloride - 2،2'-azobis (2-آمیدین پروپان) دی هیدروکلرایدHPLC (high-performance/pressure liquid chromatography) - HPLC (کروماتوگرافی مایع با کارایی بالا / فشار)ROS - ROShuman serum albumin - آلبومین سرم انسانیMonoclonal antibody - آنتی بادی مونوکلونالOxidation - اکسیداسیونTryptophan - تریپتوفانKYN - جنسیتAnalytical chemistry - شیمی تجزیهExcipients - عضلاتreversed phase - فاز معکوسFormulation - فرمولاسیونICH - منChemical stability - پایداری شیمیاییInternational Conference on Harmonization - کنفرانس بین المللی هماهنگیkynurenine - کینورینینReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Characterization of N-Acetyl-Tryptophan Degradation in Protein Therapeutic Formulations Characterization of N-Acetyl-Tryptophan Degradation in Protein Therapeutic Formulations](/preview/png/8513652.png)
چکیده انگلیسی
N-Acetyl-tryptophan (NAT) is used as a stabilizer for preparations of human serum albumin and has more recently been demonstrated to provide oxidative protection for labile Trp residues in monoclonal antibodies. As a component in the formulations of protein therapeutics, NAT is sacrificially degraded; therefore, understanding the identity and quantity of NAT degradants potentially formed in these drug products is essential to understanding the potential patient impact of this additive. Here, we report a simple reversed-phase chromatography approach that allows systematic investigation of NAT degradation in relevant formulations under stressed conditions. Screening a panel of NAT-containing samples following a variety of forced stress conditions led to a range of NAT degradation from minimal (3%) to significant (83%). NAT degradants were observed to be largely conserved between oxidative and thermal stress conditions. Online mass spectrometry and standard compound synthesis allowed for identification of the major degradants in the stressed sample panel. NAT degradation was minimal under recommended storage conditions and in relevant thermal stress conditions for a representative protein therapeutic drug product, suggesting that NAT is stable under normal manufacturing, storage, and handling conditions. This work supports the use of NAT as an antioxidant in liquid drug product formulations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 12, December 2017, Pages 3499-3506
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 12, December 2017, Pages 3499-3506
نویسندگان
Kyle L. Hogan, Danielle Leiske, Cleo M. Salisbury,