Solid phase assay of urine cystine supersaturation in the presence of cystine binding drugs

Purpose: We report a new kind of assay system far urine cystine supersatura tion that is accurate in the presence of cystine binding thiol drugs. We me asured the molar ratio of cystine dissolved per mole of drug. Materials and Methods: Measured amounts of cystine crystals were incubated in buffer or urine for 48 hours with stirring. The solid phase remaining wa s pelleted by centrifugation, extracted into a high pH buffer and measured. D-penicillamine, tiopronin and captopril were added to determine their eff ect on solid phase dissolution. Results: Total cystine calculated from urine and solid measurements closely matched the amounts of cystine weighed in, meaning that the assay system s uccessfully recovered the total cystine from the 2 phases. Each drug dissol ved solid cystine in a specific and fixed proportion to its molar concentra tion in the range of 0.2 to 0.4 mM. dissolution per mM. of drug. Solution m easurements were not a reliable gauge to the actual amounts of cystine diss olved. Conclusions: Changes in solid phase cystine accurately reflect buffer or ur ine supersaturation when thiol drugs are present. The solid phase assay is a technically straightforward and reliable way of assessing cystine movemen t into and out of urine that avoids complexity of measurement and distortio ns of assay systems by drugs. This assay enables one to assess the level of drug effect and the need for a change in dosing.