Premium
Quality by design: A systematic and rapid liquid chromatography and mass spectrometry method for eprosartan mesylate and its related impurities using a superficially porous particle column
Author(s) -
Kalariya Pradipbhai D.,
Kumar Talluri Murali V. N.,
Gaitonde Vinay D.,
Devrukhakar Prashant S.,
Srinivas Ragampeta
Publication year - 2014
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201301364
Subject(s) - chromatography , ammonium formate , chemistry , mass spectrometry , quality by design , high performance liquid chromatography , ammonium acetate , analytical chemistry (journal) , reversed phase chromatography , chromatography column , elution , resolution (logic) , particle size , computer science , artificial intelligence
The present work describes the systematic development of a robust, precise, and rapid reversed‐phase liquid chromatography method for the simultaneous determination of eprosartan mesylate and its six impurities using quality‐by‐design principles. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and pH were identified. The optimization was performed for secondary influential parameters—column temperature, gradient time, and flow rate using eight experiments—to examine multifactorial effects of parameters on the critical resolution and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was found to be accurate. This study also describes other operating features of the column packed with superficially porous particles that allow very fast separations at pressures available in most liquid chromatography instruments. Successful chromatographic separation was achieved in less than 7 min using a fused‐core C 18 (100 mm × 2.1 mm, 2.6 μm) column with linear gradient elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance with the International Conference on Harmonization Q2 (R1) guidelines. The impurities were identified by liquid chromatography with mass spectrometry.