A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis.

Autor: Stafford JD; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA., Maloney TD, Myers DP, Cintron JM, Castle BC
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2011 Sep 10; Vol. 56 (2), pp. 280-92. Date of Electronic Publication: 2011 May 20.
DOI: 10.1016/j.jpba.2011.05.028
Abstrakt: A strategy for developing chromatographic methods designed to determine impurities and degradation products in active pharmaceutical ingredients and drug products is presented. Selectivity is achieved by evaluating a chromatographic space comprised of 12 stationary/mobile phase combinations. Stationary phases predicted to be orthogonal based on their hydrophobic subtraction model parameters used. The particle sizes, column dimensions, and gradient times chosen provide high peak capacities and allow operation at backpressures that can be achieved with standard instrumentation. The mobile phases utilized are compatible with MS detection and cover a wide range of pH, solvent strength, and solvent selectivity. Analyte detection is accomplished using a combination of diode array and mass spectroscopic detectors which allow mixtures of project compounds to be injected and selectively detected. Automation of data acquisition and processing is accomplished using AutoChrom software from ACD\Labs. The strategy is illustrated with detailed data from two case studies and summary data from nineteen pharmaceutical projects.
(Copyright © 2011 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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