A novel column/buffer combination for chromatographic analysis of basic drugs in simulated gastrointestinal fluids

In vitro dissolution testing of solid pharmaceutical dosage forms has become a routine aspect of data collection for new product submissions and quality control purposes. With increasing frequency, dissolution testing is performed in buffered media, including low pH simulated gastric fluid and/or alkaline pH simulated intestinal fluid. High-performance liquid chromatographic separation of multicomponent formulations is the most convenient method of quantitation for dissolution samples in such aqueous media; however, particularly in the analytical methodology of drugs containing basic moieties, the direct injection of dissolution media may cause spurious peaks, base line disturbances, and other manifestations of column disequilibration. Using a column packing consisting of 16% w/w alumina in unbonded silica and aqueous mobile phases buffered with monofluorophosphate ion, it is possible to achieve stability in a system exposed to injections differing from the mobile phase in pH and composition.