Determination of quaternary alkylammonium compounds by capillary zone electrophoresis and indirect UV detection as a real alternative to ion chromatography with suppressed conductivity detection

A capillary electrophoretic (CE) method for the determination of residual mid-chain alkyltrimethylammonium compounds in the pharmaceutical product Welchol™ (an alkylated, crosslinked polyallylamine) was developed, validated and compared with the existing ion chromatographic (IC) method with suppressed conductivity detection. Excellent reproducibilities of migration times (RSD<0.5% within a series of 55 sample injections) and relative peak areas (RSD<2%) make the method suitable for quality control as a real alternative to IC. Limits of quantification of 0.01% w/w of each impurity in the active substance were achieved. Buffer systems for indirect UV detection based on creatinine as visualization reagent with different inorganic and organic acids (phosphoric, sulfuric, formic, acetic, oxalic and citric acid) and their effect on selectivity to ten quaternary ammonium compounds were studied. Selectivity changes were observed for the di- and trivalent analytes depending on the buffer applied. Also, the influence of acetonitrile, methanol, 1,4-dioxane and tetrahydrofuran on selectivity was investigated. In addition, CE–MS experiments were carried out in order to identify several impurities in the product.