title: Structural characterization of alkaline and oxidative stressed degradation products of lurasidone using LC/ESI/QTOF/MS/MS.
abstract: A selective, accurate, precise and robust stability indicating liquid chromatography assay method was developed for the monitoring of a novel antipsychotic drug, lurasidone, in the presence of its degradation products (DPs). Also, we investigated degradation behavior of the drug under various stressed conditions such as hydrolytic (acidic, basic and neutral), oxidation, photolytic and thermal. The drug was found to be degraded under base hydrolytic and oxidative conditions, while it was stable in acid and neutral hydrolytic, photolytic and thermal conditions. The method showed adequate separation of lurasidone and its DPs on Xterra C18 (150 mm × 4.6 mm i.d., 3.5 μm) column using 20 mM ammonium formate (pH 3.0): acetonitrile as a mobile phase in gradient elution mode at a flow rate of 0.6 mL/min. This method was extended to liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI/QTOF/MS/MS) for structural characterization of DPs. A total of five DPs were characterized by LC/ESI/QTOF/MS/MS studies. Most probable mechanisms for the formation of DPs were proposed. The developed method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonization Guideline Q2 (R1).
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India. Electronic address: narendra.talluri@gmail.com.
authors.forename: M V N
authors.initials: MVN
authors.lastname: Kumar Talluri
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research, IDPL R&D Campus, Balanagar, Hyderabad 500037, India.
authors.forename: Shireesha
authors.initials: S
authors.lastname: Dharavath
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: B
authors.initials: B
authors.lastname: Prasanth
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: R
authors.initials: R
authors.lastname: Srinivas
mesh_terms: D000468:Alkalies / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006358:Hot Temperature; D006868:Hydrolysis; D054833:Isoindoles / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D000069056:Lurasidone Hydrochloride; D010084:Oxidation-Reduction; D010782:Photolysis; D011619:Psychotropic Drugs / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013844:Thiazoles / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000468:Alkalies; D054833:Isoindoles; D011619:Psychotropic Drugs; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride
keywords: Degradation products; HPLC; LC/ESI/QTOF/MS/MS; Lurasidone; Stressed degradation