MULTIPLE RESPONSE OPTIMIZATION APPLIED TO THE DEVELOPMENT OF HEADSPACE CAPILLAR GAS CHROMATOGRAPHY METHODS FOR ANALYSIS OF RESIDUAL SOLVENTS

CARLA M. TEGLIA; MILAGROS MONTEMURRO; MA. SILVIA CÁMARA; MA. MERCEDES DE ZAN; JUAN C. ROBLES

Rosario

Congreso; 2º Reunión Internacional de Ciencias Farmacéuticas; 2012

In developing a GC method, optimization may be applied to reduce the analysis time achieving desirable values for critical chromatographic parameters. The need of taking into account different aspects of the analysis at the same time calls for the use of multicriteria optimization. Experimental design, specifically surface response analysis, is a valuable tool in order to deal with this scope (1). In addition, when different objective functions have to be optimized, the so called ?Derringer?s desirability function? is a powerful strategy (2). Volatile organic solvents, which are widely used in the manufacture of drug substances or excipientes are not completely removed by practical manufacturing techniques. The residue of these solvents offers no therapeutics benefit, but can present a serious potential hazard to human health. Therefore, it is essential to ensure they are below the acceptable levels stipulated in worldwide regulatory standards, such as ICH and USP (3). In this work a gas chromatographic method was developed, optimized and will be validated for its application in the simultaneous determination of methanol, ethanol, ethyl ether, acetone, 2-propanol, acetonitrile, methylene chloride, hexane, isopropyl ether, ethyl acetate, chloroform, tetrahydrofuran, cyclohexane, benzene, heptane, isooctane, triethylamine, 1-butanol, trichloroethylene, 1,4-dioxane, propyl acetate, pyridine, toluene, ethylene glycol, carbon tetrachloride, N,N-dimethylformamide and xylene, in raw material.