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Development and validation of an analytical method for quantification of potential genotoxic impurity 4‐dimethylaminopyridine in linagliptin active pharmaceutical ingredient using Hydrophilic Interaction Liquid Chromatography
Author(s) -
AlSabti Bashar,
Harbali Jehad
Publication year - 2020
Publication title -
separation science plus
Language(s) - English
Resource type - Journals
ISSN - 2573-1815
DOI - 10.1002/sscp.202000056
Subject(s) - linagliptin , detection limit , chromatography , active ingredient , chemistry , impurity , reagent , pharmaceutical formulation , high performance liquid chromatography , organic chemistry , medicine , bioinformatics , endocrinology , biology , diabetes mellitus , type 2 diabetes mellitus
A sensitive analytical method was developed to estimate the potential genotoxic impurity 4‐dimethylaminopyridine in linagliptin pharmaceutical ingredient. 4‐Dimethylaminopyridine is a reactive reagent used in synthesis of linagliptin. Sensitivity of the studied method was excellent at a level of 30 ppm of 4‐dimethylaminopyridine relative to linagliptin when samples of linagliptin were prepared at 10.0 mg/mL. A silica (150 mm × 4 mm, 3 µm) column was used to analyze the samples in hydrophilic interaction liquid chromatography mode. A mobile phase of water–acetonitrile (15:85, v/v) containing 10.0 mM ammonium acetate was prepared and adjusted to pH 6.2. Flow rate of the method was 1.3 mL/min and the ultraviolet detector was set at 258 nm. This method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines in terms of detection limit, quantitation limit, linearity, precision, accuracy, specificity, and robustness. The method had excellent linearity in the concentration range of 15–450 ppm with a correlation coefficient of 0.999. Detection limit and quantitation limit were 4.46 and 14.87 ppm, respectively.