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Quantitative determination of potential genotoxic impurity 3‐aminopyridine in linagliptin active pharmaceutical ingredient using HILIC–UV
Author(s) -
AlSabti Bashar,
Harbali Jehad
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4930
Subject(s) - chemistry , detection limit , chromatography , linagliptin , calibration curve , active ingredient , ammonium formate , impurity , ammonium acetate , hydrophilic interaction chromatography , acetonitrile , high performance liquid chromatography , organic chemistry , medicine , endocrinology , biology , diabetes mellitus , type 2 diabetes mellitus , bioinformatics
This study aimed to develop an analytical method to determine the quantity of the impurity 3‐aminopyridine (3AP). 3‐Aminopyridine is a reactive reagent in the synthesis of linagliptin. The method was sensitive at level of 30.0 ppm of 3AP relative to linagliptin. The analysis was carried out using hydrophilic interaction liquid chromatography. The analytical column was Tracer Extrasil Silica (150 × 4.0 mm, 3 μm). A mobile phase of water–acetonitrile (10:90, v/v) containing 10.0 mM ammonium acetate was prepared and adjusted to pH 6.0. A UV detector was used to detect the amount of 3AP at a wavelength of 298 nm. Validation of the method was performed as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use in terms of detection limit, quantitation limit, linearity, accuracy, precision, specificity and robustness. The calibration curve was linear ( r 2 = 0.999) for 3AP concentration in the range of 30.0–450.0 ppm. This method showed a good sensitivity with a detection limit and a quantitation limit of 7.5 and 25.0 ppm, respectively.