RUGGEDNESS TESTING OF GAS-CHROMATOGRAPHIC METHOD FOR RESIDUAL SOLVENTS IN PHARMACEUTICAL SUBSTANCES

Ruggedness testing is performed on a gas chromatographic method for th e quantitative determination of residual solvents in steroids. Eight e xperimental variables or factors which were expected to influence the quantitative results were selected. These factors were divided into tw o independent groups, i.e. four factors related to the injection proce ss and four factors related to separation and detection. In order to d etermine interaction between factors and quadratic effects, a central composite design was selected for the set-up of the experiments. Becau se in the method an internal standard is used, relative peak area was used as response. A deviation of up to 2.5 % per factor for the quanti tative results was regarded as acceptable. Other responses studied are related to the system suitability. Observed main, quadratic and inter action effects were translated into rugged intervals of the experiment al variables by graphical presentation. It was found that besides main effects significant interaction effects were present, for example bet ween the temperature of the injector and the split-flow. Interaction e ffects can easily result in the reduction of the rugged intervals by a factor of 2. The calculated rugged intervals were compared with the p recision of the instrument or factor settings in order to estimate the ruggedness of the factors. Eventually, the maximum effect of the vari ation in the instrument settings on the quantitative results regarding the precision of the factor settings was found to be only 2.2 %. Over all, the method proved to be rugged for most factors, except for the s plit-flow of the injector for which the method was only rugged to a li mited extent.