Additional Impurities Identified in Borocaptate Sodium

Abstract

Reliable quality control has long been an issue with the production of borocaptate sodium (BSH) because of the toxicity associated with the degradation products of BSH^1,2. The quality control issues have largely centered around the oxidation of BSH to the dimer, BSS, and oxidized dimer BSSO. A typical determination of the “purity” of the BSH drug primarily identifies the oxidation products and some reaction intermediates by high pressure liquid chromatography (HPLC)^1,3. Occasionally, the HPLC chromatograms of BSH show additional peaks which result from compounds that have not yet been identified³. Because the quality control analyses are performed on most BSH prior to it’s use, there should be a reasonable level of confidence that BSH can be administered safely, even at relatively high concentrations if the oxidation products are the primary causes of toxicity. In practice, some toxic effects have been noted in human patients administered BSH at high doses including nausea⁴, chest pain^4,5, and flushed faces⁵. Recent work has indicated that high doses of BSH caused several cardiac abnormalities in rats⁶. Five dogs unexpectedly died during, or soon after, the administration of ¹⁰BSH at a dose of 100 mg ¹⁰B/kg body weight. In a follow up study, an instrumented dog was administered BSH at a dose of 555 mg B/kg without fatal cardiotoxicity although some cardiac effects were observed⁷.