Alkaline degradation of lyophilized DMSA prior to labeling with 99m Tc: Identification and development of the degradation pathway by HPLC and MS.

INTRODUCTION: Complexes of technetium-99m (99mTc) with meso-dimercaptosuccinic acid (DMSA) have been widely used as diagnostic agents in nuclear medicine. The degradation products (DP) of DMSA formed under different forced conditions have been identified through HPLC-DAD and LC-MSn studies. In this study, the DMSA kit was subjected to forced degradation under hydrolysis conditions as prescribed by the International Conference on Harmonization (ICH) guideline Q1A.

METHODS: Chromatographic separation was accomplished on a reverse phase Shim-Pack VP-ODS (150 mm × 4.6 mm; 5 μm) analytical column using the gradient elution method. LC-MSn analysis was performed using an Esquire 3000 Plus ion trap mass spectrometer, operating under electrospray ionization (ESI).

RESULTS: No products were found under acidic or neutral stress conditions. All the products found were identified through LC-MSn analyses and their fragmentation pathways were proposed. The DMSA standard degraded into an adduct DMSA dimer (2DMSA[-2H+Na]+ ) and adduct DMSA bound to fumaric acid and dithioglucolic acid (DTGA). In the DMSA kit, the degradation products were dimers and trimers of DMSA with tin. A possible degradation pathway is presented.

CONCLUSIONS: This method proved to be convenient and effective since it provided fast and efficient separation of DMSA from its degradation products. The degradation studies carried out were able to delineate the stability of the DMSA standard and the DMSA kit.