LC–MS-MS Characterization of Forced Degradation Products of Fidarestat, a Novel Aldose Reductase Inhibitor: Development and Validation of a Stability-Indicating RP-HPLC Method

An accurate, precise, robust and selective stability-indicating liquid chromatographic (LC) method has been developed for the monitoring of fidarestat in the presence of its forced degradants. The drug was subjected to hydrolysis (acid, alkali and neutral degradation), oxidation, photolysis and ther...

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Bibliographic Details
Published in:Journal of chromatographic science 2015-10, Vol.53 (9), p.1588-1596
Main Authors: Talluri, M.V.N. Kumar, Khatoon, Lubna, Kalariya, Pradipbhai D., Chavan, Balasaheb B., Ragampeta, Srinivas
Format: Article
Language:English
Subjects:
Aldehyde Reductase - antagonists & inhibitors
Chromatography, High Pressure Liquid - methods
Chromatography, Reverse-Phase - methods
Drug Stability
Hydrolysis
Imidazolidines - analysis
Imidazolidines - chemistry
Linear Models
Oxidation-Reduction
Photolysis
Reproducibility of Results
Sensitivity and Specificity
Tandem Mass Spectrometry - methods
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Summary:An accurate, precise, robust and selective stability-indicating liquid chromatographic (LC) method has been developed for the monitoring of fidarestat in the presence of its forced degradants. The drug was subjected to hydrolysis (acid, alkali and neutral degradation), oxidation, photolysis and thermal stress conditions. The drug degraded significantly under hydrolytic (basic, acidic and neutral) and oxidative stress conditions, whereas it was found to be stable in photolytic and thermal conditions. The chromatographic separation was achieved on a Grace C18, (250 mm × 4.6 mm × 5 μm) column using gradient mobile phase system consisting of 10 mM of ammonium acetate buffer at pH 4 and acetonitrile at a flow rate of 1 mL/min with UV detection at 283 nm. The developed method was extended to liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC–QTOF–MS-MS) for characterization of all the degradation products. A total of five new degradation products were identified and characterized by LC–QTOF–MS-MS. The developed LC method was validated as per ICH guideline Q2 (R1). The proposed method was found to be successively applied for the quality control of fidarestat in bulk drug analysis.
ISSN:0021-9665
1945-239X
DOI:10.1093/chromsci/bmv061