title: Identification and characterization of forced degradation products of pralatrexate injection by LC-PDA and LC-MS.
abstract: Pralatrexate (PTXT) is an antineoplastic folate analog and the chemical name is (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl] benzoyl] amino] pentanedioic acid. Degradation products of PTXT drug product (DP) under different forced degradation conditions have been studied using LC-PDA and LC-MS techniques. PTXT DP was subjected to forced degradation under the conditions of hydrolysis, photolysis, oxidation, and heat in accordance with ICH guidelines. The LC-MS compatible HPLC method was developed and stressed solutions were chromatographed on reversed phase HPLC. The degradation products were monitored at a wavelength of 242nm. Stress study revealed that PTXT was sensitive towards acid, alkali, peroxide, light and heat. The degradation impurities (I-IX) were identified and characterized using LC-PDA and mass spectral data.
authors.affiliation: Centre for Chemical Sciences & Technology, Institute of Science & Technology, JNTUH, Kukatpally, Hyderabad-500 085, Telangana, India; Gland Pharma Ltd., Research and Development, D.P.Pally, Hyderabad-500 043, Telangana, India. Electronic address: sastryrvrp@glandpharma.com.
authors.forename: R V R Prabhakara
authors.initials: RVRP
authors.lastname: Sastry
authors.affiliation: Gland Pharma Ltd., Research and Development, D.P.Pally, Hyderabad-500 043, Telangana, India.
authors.forename: C S
authors.initials: CS
authors.lastname: Venkatesan
authors.affiliation: Gland Pharma Ltd., Research and Development, D.P.Pally, Hyderabad-500 043, Telangana, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Sastry
authors.affiliation: Gland Pharma Ltd., Research and Development, D.P.Pally, Hyderabad-500 043, Telangana, India.
authors.forename: K
authors.initials: K
authors.lastname: Mahesh
mesh_terms: D000630:Aminopterin / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D000630:Aminopterin
keywords: Degradation products; Forced degradation; LC-PDA; LC–MS; Pralatrexate