DETERMINATION OF MIZOLASTINE, A NEW ANTIHISTAMINIC DRUG, IN HUMAN PLASMA BY LIQUID-LIQUID-EXTRACTION, SOLID-PHASE EXTRACTION AND COLUMN-SWITCHING TECHNIQUES IN COMBINATION WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

For the determination of mizolastine yl]-4-piperidinyl]methylamino]-4( 3H)-pyrimidinone, SL 85.0324), a new antihistaminic drug, in human pla sma, three methods were developed based on liquid-liquid extraction, s olid-phase extraction and column-switching in combination with high-pe rformance liquid chromatography with ultraviolet detection. The liquid -liquid extraction method included a back-extraction step that preconc entrates the drug into a small aqueous volume, resulting in very high sensitivity (0.5 ng/ml of plasma); it can be used in conventional bioa nalytical laboratories that do not have sophisticated automatic device s. The solid-phase extraction method is performed by using a robotic s ystem (Benchmate). It is completely automated from the initial samplin g to the final injection into the chromatograph. It has a good sensiti vity (1 ng/ml of plasma), but requires an expensive apparatus and skil led analysts. The column-switching method is based on a solid-phase ex traction performed on-line with chromatographic analysis; it is not co mpletely automatic, because some operations are performed manually. Th e device required for valve switching is not expensive and can be mana ged by a simple integrator or a personal computer; it is very easy to use and affords a sensitivity (2.5 ng/ml of plasma) that generally sat isfies the needs of pharmacokinetic investigations of mizolastine. The conditions were similar for all the three methods: a C-8 type column, an eluent of phosphate buffer and acetonitrile, and a spectrophotomet ric ultraviolet detector operated at 285 nm.