This blog post features an answer to a question sent in by a customer on counter ion analysis in pharmaceutical applications:
When it comes to counter ion analysis, how do I determine whether to use ion chromatography (IC) or high performance liquid chromatography (HPLC)?
Separation of inorganic counter ions from other inorganic counter ions or inorganic ionic impurities
This can be accomplished in several ways. The best selectivity and sensitivity will likely be achieved using an ion exchange separation combined with suppressed conductivity detection. Because of the corrosive nature of the mobile phases involved, an IC system is the optimal choice. Alternatively, if the impurity levels are at low ng levels and >0.01%, this application can be achieved using either hydrophilic interaction liquid chromatography (HILIC) columns or columns designed specifically for the separation of pharmaceutical relevant counterions (for example, the Thermo Scientific Acclaim Trinity columns), and charged aerosol detection.
Separation of organic counter ions and their impurities
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The choice here depends on the level of impurities to be measured. For the ultimate in sensitivity for ionic species, an IC system with suppressed conductivity is your best choice. If the analyte contains no chromophore or a weak one (resulting in weak UV absorbance), then HPLC in combination with HILIC columns or columns designed specifically for the separation of counter ions (for example, the Thermo Scientific Acclaim Trinity columns), and detection by charged aerosol detection offers greater flexibility. For volatile analytes that possess a strong chromophore, UV detection can be used.
Simultaneous analysis of an Active Pharmaceutical Ingredient (API) and its counter ion
This application is best achieved using either a HILIC or a mixed-mode column (for example the Thermo Scientific Acclaim Trinity column) on a HPLC/UHPLC system. For the ultimate in analytical flexibility, the system should include both a UV detector (for volatile APIs that possess a strong chromophore) and a Thermo Scientific Charged Aerosol Detector (CAD) (for nonvolatile APIs that possess a weak chromophore). The charged aerosol detection would specifically target in addition the often non-absorbing counter ions, such as sodium or chloride.
Complementary detection methods for counter ions
You can also apply hyphenated mass spectrometric (MS) detection with all three applications, which adds an additional level of security in the identification of the components or offers lower detection limits. Suitable MS detectors in this care are the single stage quadrupole instruments and triple stage quadrupole instruments.
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