title: 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.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India narendra.talluri@gmail.com narendra@niperhyd.ac.in.
authors.forename: M V N Kumar
authors.initials: MV
authors.lastname: Talluri
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India.
authors.forename: Lubna
authors.initials: L
authors.lastname: Khatoon
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India.
authors.forename: Pradipbhai D
authors.initials: PD
authors.lastname: Kalariya
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India.
authors.forename: Balasaheb B
authors.initials: BB
authors.lastname: Chavan
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India NCMS, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ragampeta
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004355:Drug Stability; D006868:Hydrolysis; D048289:Imidazolidines / Q000032:analysis* / Q000737:chemistry*; D016014:Linear Models; D010084:Oxidation-Reduction; D010782:Photolysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D048289:Imidazolidines; C077139:fidarestat; D000449:Aldehyde Reductase