کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1199177 1493563 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of an in vitro liquid chromatography–mass spectrometry method to evaluate stereo and chemical stability of new drug candidates employing immobilized artificial membrane column
ترجمه فارسی عنوان
توسعه یک روش اسپکترومتری جرمی کروماتوگرافی مایع در محیط آزمایشگاهی برای ارزیابی استریو و پایداری شیمیایی نامزدهای جدید دارو با استفاده از ستون غشایی مصنوعی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی


• A method to evaluate stability of chiral compounds in gastrointestinal simulated fluids is reported.
• The use of an IAM column confirm the influence of a phospholipids environment in these studies.
• MS coupling enhances selectivity and efficacy.
• Application to new pharmaceutical compounds.

A stopped-flow HPLC method was developed to evaluate configurational and chemical stability of pharmaceutical compounds employing immobilized artificial membranes (IAM) column to simulate conditions that pharmaceutical compounds will meet in vivo. The method was applied to recent developed chiral 5-arylbenzothiadiazine derivatives possessing high positive allosteric modulatory (PAM) activity on AMPA receptor. In particular the stopped-flow HPLC method developed used a chiral column to separate single enantiomer of the compounds that are forced into an IAM column where configurational and chemical stability was evaluated in simulated gastrointestinal fluids (pH 1.2 and 6.8 at 37.5 °C) to simulate in vivo conditions. The results were compared to those obtained by dynamic and off-column methods to evaluate the effects of stationary phases on kinetic constant of enantiomerization and hydrolysis. The results suggested that the phospholipids environment of IAM stationary phases, which mimes biological membrane, greatly influence the hydrolysis process increasing the chemical stability of tested compounds while no influence on enantiomerization kinetic was observed. Therefore it is possible to suppose that 5-arylbenzothiadiazine derivatives should not hydrolysed in vivo while they should rapidly racemized in aqueous solvents. The method could represents a rapid and value tool to predict chemical and configurational stability of new chemical entities to decrease the number of animal studies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1363, 10 October 2014, Pages 216–225
نویسندگان
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