Determination of 2-mercaptopropionylglycine in plasma and urine by high-performance liquid chromatography

The pharmacokinetics of tiopronin as such is unknown

“…From analytical studies [1,2,3], however, and from comparison with other thiols it can be deduced that in biological fluids several molecular species of tiopronin will be found including a) tiopronin as a free thiol (T-SH), the administered form, b)tiopronin as a symmetrical disulphide (T-S-S-T), or as mixed disulphide (T-S-S-R) with another low-molecular thiols (R-SH), such as cysteine and glutathione, and c) tiopronin as mixed disulphide with proteins (T-S-S-P) bearing a free thiolgroup.No method for the analysis of the free thiol (a) in plasma has yet appeared. By our methods [1, 2] we quantify either the sum of low-molecular thiol and disulphides (a + b) -called non-protein-bound or unbound tiopronin -or the sum of all molecular species (a + b + c) -called total tiopronin.…”

“…Thus, in plasma a decreasing proportion of non-protein-bound [(a + b)/(a + b + c)] tiopronin was found with time after iv [4] or oral [5] administration, i. e. the relative protein binding of tiopronin increased with time after intake. Once established, the protein-binding of tiopronin in plasma is quite strong, and chemical reduction is required to split the bond and so to release the drug from proteins [1,2]. This is also the case with the disulphide part…”

“…By our methods [1,2] we quantify either the sum of low-molecular thiol and disulphides (a + b) -called non-protein-bound or unbound tiopronin -or the sum of all molecular species (a + b + c) -called total tiopronin. The urinary tiopronin method [1,2] includes all tiopronin species (a + b + c), but under normal physiological conditions the urinary excretion constitutes only a + b. No method has yet been published for specific analysis of tiopronin in biological tissues.…”

“…Carlsson, Department of Internal Medicine, University Hospital, S-581 85 Link6ping, Sweden (T-S-S-T and T-S-S-R) of non-protein-bound tiopronin [1,2]. Once the low-molecular weight species of tiopronin have mainly disappeared from plasma, the amount remaining corresponds to protein-bound tiopronin and a (low-molecular weight) fraction released from tissue to plasma.…”

“…This phase is very slow and strong tissue binding may be the reason for the very high (virtual) distribution volume. It should be noted that, due to the presence of a number of molecular species [1,2,4,5], the same time periods should be used when elimination constants are compared [6].…”