Modernizing the assay for ammonia in pharmaceuticals

The United States Pharmacopeia USP35-NF30 contains monographs for adenosine and sodium bicarbonate with imprecise and outdated color comparison assays for ammonia. In the spirit of monograph modernization we developed ion chromatography (IC) assays for ammonia that meet the requirements of the adenosine and sodium bicarbonate monographs. Ammonia, as ammonium, in a solution of adenosine is separated on a high-performance cation-exchange column and detected by suppressed conductivity. This assay requires <5min per sample and accurately determines the ammonia content of adenosine. For sodium bicarbonate a different IC method was required to determine ammonia due to the high concentration of sodium relative to ammonia in a sodium bicarbonate solution. This assay uses a high-capacity cation-exchange column that has the appropriate selectivity for determining low concentrations of ammonia in the presence of high concentrations of sodium. For both the methods, the precisions (retention time RSD<0.1%, peak area RSD<2.3%), accuracy (average recovery 70-117), limits of detection (LOD) and quantitation (LOQ), and robustness were measured according to the analytical performance requirements described in USP General Chapter <1225>.