Trace-Level Aliphatic Amines in Cationic Drugs

The analytical challenge treated in the present work consists in determining sub-ppb concentrations of low-molecular-weight amines in the presence of strongly retained cationic drugs by using ion chromatography (IC) with upstream inline coupled-column matrix elimination (CCME). In contrast to direct-injection IC, where the late elution of strongly retained drugs is a significant drawback and requires eluents with added acetonitrile, the low-pressure CCME technique — by using two preconcentration columns in series — gets by without solvent-containing eluents. In an «inverse matrix elimination» step, cationic drug and target amines are trapped on a high-capacity and a very-high-capacity preconcentration column, respectively. During the separation step, a rinsing solution flushes the drug retained on the high-capacity preconcentration column to waste. Application of CCME significantly shortens the analysis time, protects the analytical column, and improves sensitivity, as well as selectivity. Besides the determination of monomethylamine in Nebivolol hydrochloride discussed here, the CCME technique is a promising tool for determining further low-molecular-weight amines in a wide range of drugs.