کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1223059 967879 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Isolation and structure elucidation of major alkaline degradant of Ezetimibe
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Isolation and structure elucidation of major alkaline degradant of Ezetimibe
چکیده انگلیسی

This work presents the isolation and characterization of the alkaline degradant of Ezetimibe. Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, was subjected to alkaline degradation. Ezetimibe was reacted with 0.1 M methanolic sodium hydroxide solution for 10 min at 80 °C to yield alkaline degradant to an extent of 90% of initial amount of the drug taken. This degradant was detected by high performance liquid chromatography (HPLC) at relative retention time (RRT) of 1.48 with respect to Ezetimibe. HPLC method involved an isocratic elution on a Waters Symmetry C8 150 mm × 4.6 mm, 5 μm column using ammonium acetate buffer (pH 4.5, 50 mM) – acetonitrile (50:50, v/v) as the mobile phase at a flow rate of 1.0 mL/min and UV detection at 242 nm. The degradant was isolated by preparative HPLC. Purity of the isolated solid was found to be more than 99%. Structure of alkaline degradant was confirmed by LC–MS, 1H and 13C NMR and IR spectroscopy. On the basis of spectral data, the structure of the degradant was confirmed as 5-(4-fluorophenyl)-2-[(4-fluorophenyl amino)-(4-hydroxyphenyl)methyl]-pent-4-enoic acid. The route for the formation of this degradant is also proposed. Determining the structures of degradation products arouse during stress testing can be useful for preclinical discovery efforts.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 55, Issue 1, 28 April 2011, Pages 225–229
نویسندگان
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