HIGH-PERFORMANCE ION-PAIR LIQUID-CHROMATOGRAPHY - APPLICATION TO DISSOLUTION RATE AND CONTENT UNIFORMITY TESTING OF PHARMACEUTICALS

Schill and his group have shown that ion partners with good chromophores can be used to improve detection properties following separation of picrate ion pairs on cellulose columns. We have shown recently that the same concept can be transferred to high-performance liquid chromatographic conditions using small particle silica gel. In this work these systems were investigated to further substantiate some of the claims previously made concerning the predictability of chromatographic data and the application of these systems. Good correlations were found between capacity factors calculated from batch experiments and chromatographically determined data. In the course of this study the influence of temperature, pH and concentrations of picric acid [X-] on EQX and on retention data (k′, a) were studied. Trinitrobenzenesulfonic acid (TNBS) was tried as a substitute for picric acid due to its better solubility properties. It was found that the picric acid continuously formed in the trinitrobenzenesulfonic acid-stationary phase and not the TNBS is responsible for ion pair formation. The applications work revealed up to a fiftyfold enhancement in detection limits for several tropa alkaloids in comparison to reversed-phase chromatography (detection at 215 nm). In addition large concentrations of non-complexing compounds can be suppressed by using the picric acid absorption maximum at 345 nm. The method has been applied to content uniformity studies and dissolution rate testing of tablets. The reproducibility of these operations were always below 2% rel. S.D. © 1978.