Water determination in active pharmaceutical ingredients using ionic liquid headspace gas chromatography and two different detection protocols

• Headspace GC with ionic liquids diluent could evaluate water content in 4 mg samples.
• Water content was determined for 22 active pharmaceutical ingredients.
• 2 different highly efficient GC detectors, thermal conductivity detection and the new barrier ionization detector were utilized.

A rapid, accurate, precise and versatile analytical method was developed for the detection and quantification of water in solid active pharmaceutical ingredients (APIs). The headspace gas chromatography (HSGC) method utilized an ionic liquid (IL) based open tubular capillary GC column to increase sensitivity and ruggedness of this method. ILs are also utilized as the headspace solvent because of their low vapor pressure, unique physiochemical properties and high thermal stability. This method is not affected by side reactions and solubility problems which are common with Karl Fischer Titration (KFT) methods. Nor is it as limited as weight loss on drying approaches. The ability to use either/both modern thermal conductivity or barrier ion discharge GC detection provides flexibility, different dynamic ranges and sensitivity. The developed method also was shown to be broadly applicable.

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