title: Development and validation of a stability-indicating assay including the isolation and characterization of degradation products of metaxalone by LC-MS.
abstract: A stability-indicating reverse-phase high-performance liquid chromatography-mass spectrometric method was developed and validated for the assay of metaxalone through forced degradation under acidic, alkaline, photo, oxidative and peroxide stress conditions. Separation of degradation products was accomplished on a reverse-phase Phenomenex C18 (250 × 4.6 mm, 5 µm) column thermostated at 25 °C using 10 mM aqueous ammonium acetate: methanol (35:65 v/v) as mobile phase in an isocratic mode of elution. The eluents were detected at 275 nm by photo diode array detector and mass detectors connected in series. Two unknown base hydrolysis products of metaxalone were identified and characterized as (a) methyl 3-(3,5-dimethylphenoxy)-2-hydroxypropylcarbamate and (b) 1-(3,5-dimethylphenoxy)-3-aminopropan-2-ol by MS, (1)H NMR and FTIR spectroscopy. The method was validated as per International Conference on Harmonization guidelines and metaxalone was selectively determined in presence of its degradation impurities, demonstrating its stability-indicating nature.
authors.affiliation: Analytical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
authors.forename: R Nageswara
authors.initials: RN
authors.lastname: Rao
authors.forename: Hassan
authors.initials: H
authors.lastname: Farah
authors.forename: Prafulla Kumar
authors.initials: PK
authors.lastname: Sahu
authors.forename: Muthumani
authors.initials: M
authors.lastname: Janarthan
authors.forename: Ch Gangu
authors.initials: ChG
authors.lastname: Naidu
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D023303:Oxazolidinones / Q000032:analysis* / Q000737:chemistry* / Q000302:isolation & purification; D015203:Reproducibility of Results
chemical_list: D023303:Oxazolidinones; C011301:metaxalone
keywords: LC-MS; base hydrolysis; degradation products; impurity profile; metaxalone