Four process-related potential new impurities in ticagrelor: Identification, isolation, characterization using HPLC, LC/ESI-MS(n), NMR and their synthesis.

Autor: Kumar N; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Devineni SR; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Gajjala PR; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Gupta DK; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Bhat S; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Kumar R; Microlabs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Dubey SK; Microlabs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India., Kumar P; 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.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2016 Feb 20; Vol. 120, pp. 248-60. Date of Electronic Publication: 2015 Dec 24.
DOI: 10.1016/j.jpba.2015.12.037
Abstrakt: Five process-related impurities were detected in the range of 0.08-0.22% in ticagrelor laboratory batches by HPLC and LC-MS methods. These impurities were named as TIC Imp-I, -II, -III, -IV and -V. Four of these impurities, TIC Imp-I to -IV were unknown and have not been reported previously. Based on LC-ESI/MS(n) study, the chemical structures of new impurities were presumed as (1S,2S,3S,5S)-3-(2-hydroxyethoxy)-5-(7-amino-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d] pyrimidin-3-yl)cyclopentane-1,2-diol (TIC Imp-I), (1S,2S,3S,5S)-3-(7-((1R,2S)-2-(3,4-difluorophenyl)cyclopropylamino)-5-(propylsulfinyl)-3H-[1,2,3]triazolo [4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (TIC Imp-II), (1S,2R,3S,4S)-4-(7-((1R,2S)-2-(3,4-difluorophenyl)cyclopropylamino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)cyclopentane-1,2,3-triol (TIC Imp-III) and (3S,5S)-3-(7-((1R,2S)-2-(3,4-difluorophenyl)cyclopropylamino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (TIC Imp-IV). The unknown impurities were isolated from enriched crude sample by column chromatography and preparative HPLC. The complete spectral analysis, MS, 1D NMR ((1)H, (13)C and DEPT), 2D NMR (HSQC and HMBC) and IR confirmed the proposed chemical structures of impurities. Identification, isolation, structural characterization, prospects for the formation of impurities and their synthesis were first reported in this paper.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: