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Gold based drugs and their metabolites have been characterized using reversed phase, ion pairing chromatography with an inductively coupled plasma mass spectrometer as an element specific detector. For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking auranofin and in patients taking solganol. This represents the first identification of a specific gold metabolite in biological fluids taken from patients undergoing gold therapy and the first evidence that different gold drugs have common metabolites.

A sensitive method for the determination of gold-based drugs auranofin, myochrysine, and their metabolites has been developed. These gold-containing compounds were separated by reversed-phase ion-pair chromatography with tetrabutylammonium chloride as the ion-pairing agent. Gold-specific on-line detection utilized inductively coupled plasma mass spectrometry (ICP-MS). The separation conditions of pH, methanol content, concentration of the ion-pairing agent and ionic strength have been investigated. The detection limit for auranofin, the last peak in the chromatogram, was 0.3 ng. These methods were applied to the analysis of gold-containing species in urine from arthritis patients on auranofin, myochrysine or solganol therapy. The recovery of the total gold-containing species from urine was greater than 90%. Dicyanogold(I) anion, [Au(CN)2]-, was detected in the urine of several patients.

The pharmacokinetics of gold sodium thiomalate (GST) and triethylphosphine gold (auranofin; AF) are different. Gold sodium thiomalate (GST) is completely bioavailable while only 15-25% of auranofin (AF) is absorbed. Protein binding of AF occurs to a larger extent to macroglobulins than does GST and total body retention of GST is much greater than AF at six months (30% versus approximately 1%). While terminal serum half-lives are approximately equal, total body half-lives are 250 days for GST and 69 days for AF. In addition, excretory pathways contrast markedly, with 85% of AF appearing in the feces while only 30% of GST is excreted by this route; 15% of AF gold appears in the urine and approximately 70% of GST gold is excreted via this route. With all the above differences one would expect that organ and cellular distribution of these compounds would differ. While gold from both drugs is concentrated in kidney, the percent of the dose found in the kidneys is less for AF than GST, at least in animals (0.4% vs 4.8%). Minute quantities are found in other organs but more study is needed to more clearly define organ distribution of these gold compounds, particularly in man.

A method is described for determining the organic acid profile of synovial fluid. The method requires 50--100 microgram of sample and involves ion exchange for isolation of the acids followed by combined capillary column gas chromatography--mass spectrometry. Normal synovial fluid and synovial fluid from patients with rheumatoid arthritis show a similar qualitative pattern of acids (mainly fatty acids) resembling the pattern found in serum. The concentrations of the organic acids in the abnormal synovial fluids are 5--10 times higher than those in the fluid from the normal joints. In patients receiving treatment with gold thiomalate, free thiomalate was excreted in the urine. The release of this thiol upon gold therapy is of consequence for the further understanding of the mechanism of action of certain drugs against rheumatoid arthritis.