Online Removal of Non-volatile Additives from LC Mobile Phases for Improved Compatibility with Mass Spectrometry for Pharmaceutical and Biopharmaceutical R&D

Monday, March 08, 2021: 8:30 AM - 6:00 PM

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Description

The use of low UV background acidic additives (e.g. perchloric acid and phosphoric acid) in Reversed Phase Liquid Chromatography (RPLC) for related substances methods can improve selectivity and efficiency, and result in short run times. However, these additives are non-volatile and therefore not compatible with electrospray ionization mass spectrometry. Beyond the challenge of initial method development, problems of compatibility arise when legacy methods which use non-volatile additives require MS analysis. Switching acidic additives in developed methods can cause changes in retention time to low level impurities leading to further time being spent on method development. In this work, simple ion suppressor technology found in ion chromatography systems has been shown to remove non-volatile additives such as phosphoric acid for pairing of LC with MS. Electrolytically regenerated suppressors (ERS) (commercial and prototype) were tested for their compatibility to organic solvent and varying concentrations of phosphoric acid. Low level impurities (0.05%, w/w%) were detected via mass spectrometry with mobile phases composed of up to 1% phosphoric acid in water. A range of molecules with various pKa’s were tested to understand the effect of the suppressor design on the analyte chromatographic peak shape and recovery. The ability of the ERS to allow non-volatile additives to be paired with mass spectrometry has demonstrated the technique’s potential to be used in pharmaceutical R&D for impurity identification and tracking.

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Additional Info

Keywords: Please select up to 4 keywords ONLY:
Biopharmaceutical,Chromatography - Other,GLP/GMP,Method Development