Statistical optimization of a reversed-phase ion-pair liquid chromatographic method for the analysis of tolmetin sodium in dosage forms.

A quantitative liquid chromatographic method in which tolmetin sodium is separated from an internal standard on a C18 column with detection at 317 nm has been developed with the aid of two statistical optimization procedures. The effects of simultaneously varying the pH, methanol-water ratio, and the concentrations of buffer and ion-pair reagent in the mobile phase were studied. A two-level factorial design was used to investigate the interactions among the variables, and the sequential simplex procedure was used to optimize the separation. A novel quality criterion was developed for the simplex optimization. Using synthetic mixtures, the mean recovery value +/- S.D. (n = 6) of tolmetin sodium was 98.7 +/- 0.19% for tablets and 98.5 +/- 0.12% for capsules. The assay results for commercial tablets and capsules were comparable to those obtained by the USP XXI procedure.