DETERMINATION OF AMISULPRIDE, A NEW BENZAMIDE DERIVATIVE, IN HUMAN PLASMA AND URINE BY LIQUID-LIQUID-EXTRACTION OR SOLID-PHASE EXTRACTION IN COMBINATION WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND FLUORESCENCE DETECTION - APPLICATION TO PHARMACOKINETICS

Amisulpride (SOLIAN) belongs to the benzamide series and shows antisch izophrenic and antidepressant (anti-dysthymic) properties in man. Two methods suitable for pharmacokinetic investigations are proposed for t he determination of amisulpride in human plasma. For the liquid-liquid extraction (LLE) based method, the plasma, added with the internal st andard (an amisulpride analogue) is alkalinised with NaOH and extracte d with a diethyl ether-chloroform mixture. The organic phase is remove d, evaporated to dryness and redissolved in an acidic phosphate-aceton itrile mixture that, after a back-washing step with n-hexane, is injec ted onto the HPLC column (C-18 BDS type) connected with a fluorimetric detector. The second method is based on an automatic solid-phase extr action (SPE) performed on an ASPEC device. The plasma sample, diluted with a pH 9 berate buffer, is loaded onto a disposable SPE C-18 100-mg column. The analytes of interest (amisulpride and internal standard), after two washing steps with different solvents, are recovered in pur e methanol; after evaporation to dryness, the residue is dissolved in an acidic phosphate buffer and injected onto the chromatographic appar atus already described. The limit of quantitation (LOQ) is 0.5 ng ml(- 1) for both methods; a linear correlation between concentrations and d etector response has been demonstrated in the range 0.5-640 ng ml(-1) for LLE, which is the most used method; for SPE methods, less used, li nearity has been assessed in the plasma range of 0.5-160 ng ml(-1).