Evaluation of Methods for the Simultaneous Analysis of Cations and Anions Using HPLC with Charged Aerosol Detection and a Zwitterionic Stationary Phase

This paper describes the development and qualification of a method capable of analyzing inorganic ions as salts and counterions of both active pharmaceutical ingredients and other compounds such as lysine. The use of a polymeric zwitterionic column with a binary high-performance liquid chromatography gradient enables the separation of several anions and cations in a single run. A generic gradient (method #1) was developed and validated with respect to specificity, correlation, intermediate precision, accuracy, and sensitivity (limits of quantitation and detection) for four anions and two cations. Furthermore, the ability to alter chromatographic selectivity by simple gradient manipulation (without altering the mobile phase composition or column type) is demonstrated for nine anions and three cations (method #2). The simultaneous measurement of cations and anions at the parts per billion level using the Corona charged aerosol detector with zwitterionic chromatography-polymeric hydrophilic interaction chromatography is a viable alternative to traditional techniques used for ion analysis.