Mitigating the effects of organic solvents in sample diluents for ion chromatography: A comprehensive study and guidelines for optimization

Ion Chromatography (IC), the gold standard for the separation and analysis of ionic species, has been extensively used for detection of ions in industrial applications. Pharmaceutical samples with limited water solubility often require the use of organic solvents as diluents, which can pose significant challenges on IC analysis. Herein, the effects of various organic solvents as sample diluents in IC for anion analysis are systematically investigated. Electrochemically stable solvents such as 2-propanol (IPA), acetone, and dimethyl sulfoxide (DMSO) were found to have the least impact on the IC baseline. For solvents with a greater impact, a solvent dilution device (SDD) has been designed to minimize their effects. The device effectively diluted the organic solvents before they reached the suppressor electrode, reducing the generation of oxidized products. The results showed that the baseline stability and separation efficiency of IC can be maintained when using a wide range of organic solvents as diluents. Notably, the use of a solvent dilution device enabled good recovery of ions in various active pharmaceutical ingredients and significantly enhanced the signal to noise ratio of early-eluting ions compared to analyses conducted without the device. Guidelines are proposed to minimize the impact of organic solvents in IC sample preparation and anion analysis. The study also investigates the origin of impurity peaks introduced by the organic solvents and demonstrated the effectiveness of an ion-exchange resin treatment for their removal. Overall, this study provides insights for the use of organic solvents as IC diluents and offers practical solutions to overcome their challenges in pharmaceutical applications.