کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5134983 1493414 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Study of relative response factors and mass balance in forced degradation studies with liquid chromatography/photo-diode array detector/evaporative light scattering detector/mass spectrometry system
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Study of relative response factors and mass balance in forced degradation studies with liquid chromatography/photo-diode array detector/evaporative light scattering detector/mass spectrometry system
چکیده انگلیسی


- Use of a multi-detection technique to monitor degradation reactions and quantify non-chromophoric compounds.
- A novel technique for estimating RRFs by combining UV detector with a concentration sensitive detector (ELS.
- Determination of accurate mass balance by applying experimentally derived RRFs for quantification of degradation products.
- Illustration of the stereospecificity of acidic and oxidation degradation reactions by quantification of cis/trans isomers.

A case study was performed using photodiode array detection (PDA) in combination with evaporative light scattering (ELS) detection and mass spectrometry (MS) to assess both mass balance and the relative response factors (RRFs) in the forced degradation studies of the drug substance, glimepiride. The RRF value, which is the ratio of the response factor of the impurity to that of the API, was first determined using calibration curves of standards. This conventional technique was compared to a second, multi-detection technique, which used the PDA and ELS detectors to determine both the ultraviolet (UV) peak area and the concentration (based on measurement by ELS) in a single analysis. The resulting RRF values were then applied to forced degradation studies (acidic hydrolysis and oxidation) of glimepiride drug substance. This analysis was used to assess mass balance as well as impurity quantification. The impact of applying impurity RRF values was evaluated and found to have a significant impact on the percent of impurity quantified and on mass balance calculations at higher degradation levels. In addition, MS was used to quantify a non-chromophoric by-product and assess its impact on mass balance. Analysis of the forced degradation studies by MS detection also provided confirmation of the degradation pathway with new insights. Specifically, MS revealed differences in the stereoselectivity of the degradation processes: the acidic hydrolysis degradation was found to be stereoselective with the formation of the trans by-product while the oxidation degradation produced both the cis/trans isomers in a non-stereoselective reaction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1512, 25 August 2017, Pages 61-70
نویسندگان
, , ,