کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2486650 1114388 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NOTES: Formation of Amide- and Imide-Linked Degradation Products Between the Peptide Drug Oxytocin and Citrate in Citrate-Buffered Formulations
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
NOTES: Formation of Amide- and Imide-Linked Degradation Products Between the Peptide Drug Oxytocin and Citrate in Citrate-Buffered Formulations
چکیده انگلیسی
Citric acid is widely used to buffer pharmaceutical formulations including protein pharmaceuticals. In accelerated stability studies of the small cyclic peptide oxytocin, we have noted that additional degradation products form when oxytocin is formulated in citrate that do not form in other common buffers such as acetate and phosphate. Using high-pressure liquid chromatography combined with high-resolution and tandem mass spectrometry, we identified these degradation products as amide- and imide-linked adducts of oxytocin and citrate. The site of reaction was shown to be the N-terminal amine of cysteine. The adducts have been found to form for oxytocin formulated in citrate buffer over the pH range of 3-6; the extent of formation is greatest at a pH of 4-4.5. We have additionally identified these same adducts in samples of oxytocin formulated in citrate buffer that had been stored in the dark for 3 months at room temperature. Altogether, these results demonstrate that reaction between citrate and oxytocin leads to the formation of covalent amide- and imide-linked adducts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 3018-3022
نویسندگان
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