title: Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method.
abstract: Four impurities (Imp-I-IV) were detected using gradient HPLC method in few laboratory batches of acrivastine in the level of 0.03-0.12% and three impurities (Imp-I-III) were found to be known and one (Imp-IV) was unknown. In forced degradation study, the drug is degraded into four degradation products under oxidation and photolytic conditions. Two impurities (Imp-III and -IV) were concurred with process related impurities whereas Imp-V and -VI were identified as new degradation impurities. Based on LC-ESI/MSnstudy, the chemical structures of new impurities were presumed as 1-[(2E)-3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}prop-2-en-1-yl]pyrrolidin-1-ium-1-olate (Imp-IV), 1-{[3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}oxiran-2-yl]methyl}pyrrolidin-1-ium-1-olate (Imp-V) and 2-[2-(4-methylphenyl)-3-[(1-oxidopyrrolidin-1-ium-1-yl)methyl]oxiran-2-yl]-6-[(1E)-3-oxobut-1-en-1-yl]pyridin-1-ium-1-olate (Imp-VI), and confirmed by their synthesis followed by spectroscopic analysis, IR, NMR (1H,13C) and mass. An efficient and selective high-performance liquid chromatography method has been developed and resolved well the drug related substances on a Phenomenex Gemini C-18 (250×4.6mm, particle size 5μm) column. The mobile phase was composed of sodium dihydrogen phosphate (10mM) and methanol, temperature at 25°C, and a PDA detector set at 254nm used for detection. The method was validated with respect to specificity, linearity, precision, accuracy, and sensitivity and satisfactory results were achieved. Identification, synthesis, characterization of impurities and method validation were first reported in this paper.
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Subba Rao
authors.initials: SR
authors.lastname: Devineni
authors.affiliation: Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Shailender Kumar
authors.initials: SK
authors.lastname: Dubey
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Srivastava
authors.affiliation: Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Girish
authors.initials: G
authors.lastname: Ambulgekar
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Jain
authors.affiliation: Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Gupta
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Gurmeet
authors.initials: G
authors.lastname: Singh
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India.
authors.forename: S G
authors.initials: SG
authors.lastname: Hiriyanna
authors.affiliation: Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore, 560105 Karnataka, India. Electronic address: pramodkumar@microlabs.in.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
keywords: Acrivastine; Characterization; Forced degradation; Identification; Impurities; Method validation