Separation of drugs by packed column supercritical fluid chromatography. 1. Phenothiazine antipsychotics.

Studies of speed, resolution, and sensitivity indicate packed column supercritical fluid chromatography is a viable technique for the analysis of antipsychotic drugs. Fourteen such drugs (mostly phenothiazines) were studied from a cyanopropyl liquid chromatography packed column with a tertiary mobile phase of carbon dioxide, methanol, and isopropylamine. An arbitrary mix of 10 components was baseline resolved in approximately 11 min. Detection limits were as low as 125 ppb, with a feasible 10-fold decrease. Without the isopropylamine in the mobile phase, none of the solutes eluted. With the additive, all produced symmetrical peaks and high efficiency (i.e., > 80% of theoretical). Changing modifier concentration was the most effective physical parameter for changing retention but had little effect on selectivity. Temperature changes had a modest effect on retention but provided surprisingly large changes in selectivity, with numerous peak reversals occurring over only a 30 degrees C temperature range. In addition, temperature programming was the most effective means to optimize resolution of the 10-component mix. No noticeable loss in efficiency accompanied the temperature programs.