| Corona(TM) charged aerosol detection in high performance liquid chromatography (HPLC) has recently become commercially available, however the detection mechanisms are not well understood. The goal of this research is to better understand this new detection method for HPLC method development by determining the basic chromatographic parameters that have an effect on this detector. These include composition of the mobile phase and its relationship with the baseline signal, the determination of the amount of mobile phase that is associated with detector charging, effects on analyte response and how it they are affected by changes in mobile phase composition, the effects of volatile mobile phase additives, and determination of the actual amount of analyte that is being detected by the electrometer. In addition to developing a better understanding of charged aerosol detection, applications were examined with respect to current detection methods for HPLC, such as ultraviolet (UV) detection. The application that was chosen was Pharmaceutical Cleaning Validation, where HPLC with charged aerosol detection proved to be an acceptable technique for trace level analysis of drug substance on typical pharmaceutical manufacturing equipment surfaces. HPLC-charged aerosol detection was also examined for general pharmaceutical analysis and the ability of this technique to be fully validated to current International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and United States Pharmacopeia (USP) guidelines. Again HPLC-charged aerosol detection proved itself as an acceptable technique, and several pharmaceutical assays for in-process control, impurities, and drug substance purity were validated. |
