Analytical methods for determination of counter-ions in pharmaceutical salts

Inorganic ions as well as organic acids or bases are frequently employed as counter-ions of ionizable drug substances. Therefore, analytical methods are required to confirm production of the correct salt form and to quantify the level of the counter-ion present in each batch of drug substances manufactured. Several options exist for determination of counter-ions in pharmaceutical salts and will be discussed in this review. Ion chromatography (IC) with conductivity detection is probably the most frequently employed method for ion determination. Other techniques such as capillary electrophoresis (CE) represent an alternative to IC for determination of counter-ions in pharmaceutical salts. Due to the lack of chromophores, detection of small ions in CE is typically performed using indirect UV detection. Hydrophilic interaction chromatography (HILIC) with evaporative light-scattering (ELSD) or refractive index detection can also be used for determination of non-UV absorbing ions. Each technique will be described and their advantages highlighted. Current and future trends in measuring counter-ions in pharmaceutical salts will also be discussed.