Global optimization using Derringer's desirability function: enantioselective determination of ketoprofen in formulations and in biological matrices

A reversed-phase high-performance liquid chromatographic method for separation of the enantiomers of ketoprofen in formulations and in plas-ma matrices has been developed and optimized. A central composite design was used to develop response models and Derringer’s desirability function was then used for simultaneous optimization of chiral resolution and analysis time. This procedure enabled discovery of two separate sets of opti-mum conditions for analysis of quality-control samples and plasma samples within the experimental domain. The optimum conditions predicted for quality-control samples were acetonitrile–dipotassium hydrogen phosphate buffer (10 mΜ, pH 6.5)–triethylamine 56:44:0.05 (/ν) as νmobile phase and 1.13 mL min-1 as flow rate. Use of these conditions enabled baseline separation of the enantiomers of ketoprofen in approximately 4.2 min, which is quicker than the previously optimized method. The method was suitable for routine analysis of the enantiomers of ketoprofen in a commercial pharmaceutical preparation and in plasma samples.