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

Abstract

For the determination of mizolastine (2-[[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-4- piperidinyl]methylamino]-4(3H)-pyrimidinone, SL 85.0324), a new antihistaminic drug, in human plasma, three methods were developed based on liquid-liquid extraction, solid-phase extraction and column-switching in combination with high-performance liquid chromatography with ultraviolet detection. The liquid-liquid extraction method included a back-extraction step that preconcentrates the drug into a small aqueous volume, resulting in very high sensitivity (0.5 ng/ml of plasma); it can be used in conventional bioanalytical laboratories that do not have sophisticated automatic devices. The solid-phase extraction method is performed by using a robotic system (Benchmate). It is completely automated from the initial sampling to the final injection into the chromatograph. It has a good sensitivity (1 ng/ml of plasma), but requires an expensive apparatus and skilled analysts. The column-switching method is based on a solid-phase extraction performed on-line with chromatographic analysis; it is not completely automatic, because some operations are performed manually. The device required for valve switching is not expensive and can be managed 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 satisfies the needs of pharmacokinetic investigations of mizolastine. The conditions were similar for all the three methods: a C8 type column, an eluent of phosphate buffer and acetonitrile, and a spectrophotometric ultraviolet detector operated at 285 nm.