Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria. It is available as a generic medication. Chemically classified as a thiol containing compound and commonly referred to as N 2 mercaptopropionylglycine, tiopronin acts as a cystine binding agent that increases cystine solubility in urine. It is supplied for oral administration in tablet form and is characterized as a white to off white crystalline powder with good aqueous solubility relative to cystine; typical quality control testing for the active pharmaceutical ingredient includes identity by IR or NMR, assay by HPLC, water content by Karl Fischer, and limits for residual solvents and heavy metals in line with pharmacopeial and ICH guidance. Stability considerations include protection from prolonged exposure to air and light to limit oxidative dimerization, and formulated products are stored under conditions recommended by the manufacturer to preserve potency.
Parent: Tiopronin Reference Standard
Typical impurities and related compounds monitored during manufacture and release testing include the tiopronin disulfide dimer formed by oxidation of the free thiol, low level oxidative products such as sulfoxides, hydrolysis products and trace process related impurities from synthesis. Acceptable limits used in many API specifications are commonly set so that individual unidentified impurities do not exceed 0.5 percent by area in HPLC and total impurities do not exceed 2.0 percent by area, with specific related compounds qualified at lower limits as required by ICH Q3A and applicable pharmacopeial monographs; the disulfide dimer is often specifically quantified and typically found below 0.5 percent in controlled batches. Residual solvents and elemental impurities are controlled to meet ICH Q3C and Q3D limits respectively, and specifications should be confirmed against the current pharmacopeial monograph or manufacturer certificate of analysis.
Tiopronin is used to reduce urinary cystine concentration and prevent formation of cystine kidney stones in patients with cystinuria, as an adjunct to increased fluid intake and urinary alkalinization.
Tiopronin provides a free thiol group that forms mixed disulfides with cystine, converting poorly soluble cystine into more soluble complexes and thereby lowering the risk of crystal and stone formation.
Another name for tiopronin is mercaptopropionylglycine, often abbreviated as MPG, and it is marketed under the brand name Thiola.
Cost varies by country, dose, manufacturer and whether the product is brand or generic; out of pocket prices in the United States for generic tiopronin commonly range from roughly fifty to several hundred dollars per month depending on dose and pharmacy pricing, and insured patients should consult their insurer and local pharmacies for exact copay or formulary pricing.
