Generic Ion Chromatography–Conductivity Detection Method for Analysis of Palladium Scavengers in New Drug Substances

The revolution of palladium-catalyzed reactions in the synthesis of new molecules has created an unprecedented need for highly efficient palladium (Pd) removal processes. Metal scavengers with very selective and efficient removal properties are being extensively applied across process research and development (PR&D) to meet very tight specifications for residual Pd levels. Analytical procedures for the determination of residual Pd are well-established; however, developing methodologies to detect a variety of Pd scavengers in multicomponent reaction mixtures is currently considered an emerging challenge in pharmaceutical analysis. Herein a simple and efficient generic ion chromatography–conductivity detection (IC–CD) method on a Dionex IonPac AS19 column in conjunction with a fully aqueous eluent profile (potassium-hydroxide-based) capable of chromatographically resolving over 10 Pd scavenger species commonly used in PR&D workflows is described. Computer-assisted separation modeling using an ACD Labs/LC simulator served to generate 3D resolution maps with excellent separation conditions that matched the outcome of subsequent experimental data. Method validation experiments showed excellent analytical performance in linearity, recovery, repeatability, and LOQ/LOD. In addition, these same chromatographic conditions can separate multiple anionic species and active pharmaceutical (API) counterions along with Pd scavengers in the same experimental run. We also provide strategic examples where API counterion interferences (e.g., sulfate) can be minimized by treating the API sulfate form with barium acetate to enhance the recovery of the Pd scavenger analyte.