SIMULTANEOUS DETERMINATION OF MODAFINIL AND ITS ACID METABOLITE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY IN HUMAN PLASMA

A sensitive and selective high-performance liquid chromatographic (HPL C) method for the simultaneous quantitation of modafinil and its acid metabolite in human plasma has been developed. The method is based on a liquid-liquid extraction followed by isocratic reversed-phase HPLC w ith ultraviolet absorbance detection at 236 nm. The eluent used was ac etonitrile-water-acetic acid (150:420:12, v/v/v). The run time was 45 min. The method provided a detection limit of 0.04 mg/l for modafinil and the acid metabolite, a quantitation limit of 0.13 mg/l for modafin il and 0.14 mg/l for the acid metabolite. A good linear relationship w as obtained in the concentration range studied (0.1-20 mg/l) for both compounds and the method was sufficiently accurate and precise to supp ort clinical pharmacokinetic studies. To our knowledge this is the fir st described method for determination of modafinil and its acid metabo lite in plasma.