Quantitation of Ammonium Cations in Pharmaceutical Samples by Nonaqueous Capillary Electrophoresis with Indirect UV Detection

Abstract

A nonaqueous capillary electrophoresis (CE) method with indirect UV detection was developed specifically for quantitation of ammonium cations in pharmaceutical samples. Employing a methanol‐based background electrolyte system with options of using up to 60% of acetonitrile or 30% of tetrahydrofuran (THF) as buffer additives, allows for injection of a variety of sample matrices with organic solvents. Consequently, ammonium in most samples that have poor solubility in water can be determined by the CE method. Apparent pH* of the background electrolyte was optimized to achieve a close mobility match between the ammonium cation and the UV probe, imidazole. This provided symmetrical ammonium peak shape, and consequently, improved detection sensitivity, injection reproducibility, and resolution from possible interferences. A buffer additive, 15‐crown‐5 ether, significantly improved the resolution of ammonium from potassium interference in the methanol‐based background electrolyte system, which allowed for quantitation of ammonium in a sample that contained 10,000 times higher levels of potassium. The CE method was validated according to current pharmaceutical industry standards. The injection reproducibility and linearity in the target range were determined to be acceptable. The limit of detection (LOD) and limit of quantitation (LOQ) of ammonium cations in solutions were determined to be 50 ppb and 0.5 ppm, respectively. The method has been successfully employed for quantitation of the ammonium impurity in pharmaceutical samples.