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

Abstract

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.

Identification and characterization of in vitro and in vivo fidarestat metabolites: Toxicity and efficacy evaluation of metabolites

“…The MS/MS spectrum of protonated fidarestat in positive ESI mode shows very few product ions at m/z 235, m/z 218, m/z 192, m/z 164, and m/z 149 26 . Hence, in the present study, sample was analyzed in negative ion mode.…”

LC-MS characterization of acid degradation products of metoclopramide: Development and validation of a stability-indicating RP-HPLC method

“…A total of three degradants were produced from the MCP (denoted as I-III as per the formation). A major degradation product DP-II was formed in acid stress condition (Bakshi and Singh, 2002;Rakibe et al, 2018), which was obtained from the degradant DP-I by the hydrolysis of both amide bond and methoxy group attached to the phenyl ring system (Talluri et al, 2015). While the other degradation product DP-III was also produced in acid stress conditions due to the hydrolysis of C-N existed between the triethylamine and nitrogen of the amide group in the metoclopramide.…”