Determination of sulfinpyrazone and four metabolites in plasma and urine by high pressure liquid chromatography.

An HPLC method for the simultaneous determination of sulfinpyrazone and its p-hydroxy, sulfone, sulfide and p-hydroxysulfide metabolites in human plasma and urine samples was developed. Optimization with regard to sample preparation and chromatographic conditions was investigated. In the final procedure samples were acidified with HCl, extracted with a 1 + 1 (vol/vol) mixture of 1-chlorobutane and chloroform; urine extracts were re-extracted with citrate buffer (pH 4.5). HPLC was performed on reversed phase (RP 8) columns with a 48 + 52 (vol/vol) mixture of ethanol and citrate buffer (pH 2.5) as the mobile phase. The lower limit of detection for sulfinpyrazone and the sulfide metabolite is 10 ng/ml, for the other metabolites it is 50 ng/ml. An example of application of this procedure to pharmacokinetic studies in a volunteer receiving a single oral dose of sulfinpyrazone is given.