Determination of some tricyclic neuroleptics by reversed-phase high-performance liquid chromatography with ultraviolet and polarographic detection.

The liquid chromatographic behaviour of various neuroleptics from the classes of tricyclic dibenzothiepins, -oxepins, -selenepins and similar substances was studied in an ion-pair reversed-phase system using a C4180 chemically bonded stationary phase and a methanol-water-acetic acid mobile phase. The best separation was attained with 70% methanol, 1.8% acetic acid and water, containing 0.005 M sodium pentanesulphonate, 1.2 X 10(-4) M EDTA and 0.5 g/l Na2SO4. For the detection, an ultraviolet spectrophotometric and a polarographic detector were connected in series. The detection was carried out at 254 nm and at a potential of a dropping mercury electrode of -1.0 V (vs. Ag/AgCl). The UV detector is universal, while the polarographic detector does not respond to compounds simultaneously containing two heteroatoms (O, S) in the central seven-membered ring. The detection limits are of the order of one to tens of nanograms, the polarographic detector being somewhat more sensitive for most of the compounds; the error of the determination is a few per cent. The method was applied to the determination of isofloxythepin and oxyprothepin in pharmaceutical preparations.