Determination of pharmaceutically related compounds by suppressed ion chromatography: IV. Interfacing ion chromatography with universal detectors

This work forms the final part of a study investigating gradient elution ion-exchange chromatography of pharmaceutically relevant compounds, aiming at achieving complementary selectivity to reversed-phase HPLC. In this study the coupling of three universal detectors (electro-spray ionisation mass spectrometer (ESI-MS); corona charged aerosol detector (CAD); and evaporative light scattering detector (ELSD)) to suppressed IC using complex elution profiles with potassium hydroxide eluents is demonstrated. The non-volatile ions were removed from the eluent by the suppressor prior to detection, thus allowing a stable detector response, especially with the prototype electrolytic suppressor. The detector response for ten weakly anionic pharmaceuticals followed the expected models and the limits of detection obtained were not compromised by the use of a suppressor, yielding values below 50 ng/mL with MS, low to sub μg/mL levels with CAD and 2–20 μg/mL with ELSD (25 μL injections). When coupled to MS and CAD, the prototype electrolytic suppressor showed percentage relative standard deviations (%RSDs) in peak areas of 0.4–2.5% on average, compared to the chemical suppressor which yielded 1.5–3 fold higher %RSD values for the test analytes. The prototype electrolytic suppressor also generally exhibited wider linear response ranges than the chemical suppressor.

► Ion-exchange separations are coupled with MS, ELSD and CAD.
► An in-line suppressor is used to de-salt the eluent prior to detection.
► Stable detector baselines were obtained when gradient elution was employed.
► A new high capacity electrolytic suppressor gave optimal performance.