Use of Ellmans Reagent for verification of DMSA content in a kit compounded in a nuclear pharmacy

• Published in: The Journal of nuclear medicine (1978) Vol. 58; p. 261
• Main Authors: Galbraith, Wendy, Neely, Stephen, Dolan, GT, Gali, Hariprasad
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01-05-2017
• Subjects: Acceptance criteria; Calibration; Compounding; Confidence intervals; Dimercaptosuccinic acid; Medical diagnosis; Medical imaging; Nitrobenzoic acid; Nuclear medicine; Patients; Pharmaceuticals; Radiochemical analysis; Radioisotopes; Reagents; Scars; Statistical analysis; Technetium; Water purification
• ISSN: 0161-5505; 1535-5667

Objectives: Succimer (meso-2,3-dimercaptosuccinic acid, DMSA) commercial manufacturing has been discontinued. 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 extemporaneous compounding in a nuclear pharmacy. Methods: All methods were performed according to USP monographs and chapters. 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 syringe 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. Results: 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 content with 4 sampled vials using the Ellman's Reagent. Kits have shown stability over 45 days frozen. Conclusion: With approximately 6,000 vesicoureteral reflux pediatric patients per year in the US in need of imaging for renal scarring, a secure source of DMSA is needed. In the last year, our institution has imaged over 100 patients with compounded DMSA. We propose quantification of DMSA using Ellman's Reagent is an accurate method to determine the true quantity of functional thiol groups available for labeling with technetium. This compounding and verification method can easily be utilized in a nuclear pharmacy within their scope of practice.