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Free thiomalate is measureable in the plasma and urine of patients with rheumatoid arthritis receiving sodium aurothiomalate (Myocrisin). Plasma concentrations and urinary excretion of free thiomalate were measured in 8 patients by high-performance liquid chromatography and electrochemical detection. After an initial intramuscular dose of 20 mg sodium aurothiomalate, free thiomalate was detected in plasma within 15 min, peak levels of up to 600 nmol/l occurring at 30 min. Plasma levels declined rapidly thereafter. During the first 24 h between 2 and 16% of the injected dose of aurothiomalate was recovered in the urine as free thiomalate, maximum excretion occurring during the first hour.

The water-soluble dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) are becoming of increasing importance for the treatment of lead, arsenic and mercury poisoning. There is, however, a paucity of data about their metabolic transformation. Male rabbits were given DMSA (0.20 mmol/kg) i.m., and urine was collected over a 6-hr period. Monobromobimane derivatization, HPLC separation, and fluorescence detection, along with [U-14C]DMSA data, demonstrated that the total 14C found in the urine was distributed as 73% unaltered DMSA, 7% mercaptosuccinic acid and 6 and 14% of two unknowns. Electrolytic reductive treatment of the urine did not increase the urinary content of DMSA, indicating that oxidative biotransformation is not a major pathway for DMSA in the rabbit. This latter result is strikingly different from that for DMPS in rabbit.

The excretory fate and plasma level of thiomalate were studied after intramuscular administration of auro-14C-thiomalate to 3 patients with rheumatoid arthritis. The gold and the thiomalate parts separated in vivo, and the free thiomalate was excreted in the urine, rapidly at first and then slowly. After one day about 60% of the 14C-label had been recovered in the urine. The plasma level also declined rapidly. The results are in complete agreement with those previously described in animal experiments.