Simultaneous determination of positive and negative pharmaceutical counterions using mixed-mode chromatography coupled with charged aerosol detector.
A mixed-mode chromatography coupled with charged aerosol detector (CAD) method was developed in this work to simultaneously determine pharmaceutical counterions including both inorganic ions and organic ions in the forms of cations and anions. 25 commonly used pharmaceutical ions were studied and simultaneously separated within 20 min by this single method. A silica based mixed-mode column with reversed-phase/cation-exchange/anion-exchange modes was used. It provides reversed-phase, strong cation-exchange and weak anion-exchange properties at the same time. It also provides the HILIC behavior at high percentage of organic solvent. The effects of mobile-phase organic strength, buffer ions, ionic strength, pH and column temperature have been investigated to optimize the method as well as to understand the retention and separation mechanisms. Conventional HPLC system was used and no special chromatography system is needed. The presented method has been employed successfully for screening and quantitative analysis of counterions, unknown ionic impurities and salts in active pharmaceutical ingredients and in process control samples with excellent accuracy, precision and sensitivity. This method provides a simple, fast and generic approach to speed up pharmaceutical research and development process and enhance lab efficiency. The similar methodologies can be applied to other ion analysis.
Zhang
Ke
K
Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. zhang.kelly@gene.com
Dai
Lulu
L
Chetwyn
Nik P
NP
D000336:Aerosols / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000032:analysis / Q000737:chemistry; D009994:Osmolar Concentration; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature
D000336:Aerosols; D007477:Ions; D004364:Pharmaceutical Preparations