Compounding of DMSA Radiopharmaceutical Kits During a Shortage

Succimer (meso-2,3-dimercaptosuccinic acid, DMSA) commercial manufacturing was discontinued for 5.5 years from 2016 to 2022. This radiopharmaceutical is used in our academic health center as standard of care for diagnosing and staging renal scarring. Our objective was to validate a method to verify the content of DMSA in a cold reaction vial, referred to hereafter as a kit, after compounding in a nuclear pharmacy.

A simplified method of DMSA kit compounding was performed by passing a saturated solution of DMSA in sterile water for injection through a 0.22-micron filter after the addition of all other kit components. To verify DMSA content, we used Ellman's Reagent, 5,5'-dithio-bis-(2-nitrobenzoic acid). This compound reacts with a free thiol group at pH - 8 to produce a yellow-colored mixed disulfide product with a strong absorbance at 412 nm. A calibration curve was prepared using DMSA solutions of known concentrations and used to determine the molar concentration of DMSA in a kit. The kits were stored frozen and DMSA content was verified over 45 days.

All kits met the acceptance criteria of the USP monograph for technetium 99m succimer for administration. Statistical analysis with 0.95 power and using mean standard deviation resulted in a 95% confidence interval within ±10% of DMSA labeled content by sampling 4 vials of a batch using the Ellman's Reagent test. Kits have shown stability over 45 days frozen.