Development and evaluation of a prototype commercial condensation nucleation light scattering detector for HPLC and a corona discharge neutralizer for electrospray aerosols used with condensation nucleation light scattering detection

Condensation Nucleation Light Scattering Detection (CNLSD) has been successfully coupled to HPLC for a wide range of applications. However, there has been no commercial CNLSD detector for HPLC. In the first project, a prototype commercial CNLSD detector for HPLC based on a commercially available Nonvolatile Residue Monitor (NRM) was developed, and tested by flow injection analysis and separation systems of difficult-to-detect species including alkali metal ions, carbohydrates and neutral lipids under optimized conditions for each individual system. The prototype CNLSD detector showed great sensitivity, linearity and reproducibility, which were comparable or even better than results previously reported for a home-made HPLC-CNLSD system. These results show that the prototype CNLSD holds great promise to become a routine commercial detector for HPLC in pharmaceutical industry and other applications.;In the second project, a method of direct determination of catecholamines (CAs) by HPLC-CNLSD was developed by using a prototype commercial CNLSD detector. The separation of CAs and the performance of the prototype CNLSD were studied and optimized. The developed method showed good linearity for three catecholamines at concentrations from 0.02 to 1 mug/mL. The limits of detection (LODs) for norepinephrine, epinephrine and dopamine were 14, 17 and 17 ng/mL, respectively. The developed method could be applied for the determination of CAs in pharmaceutical formulations, and holds the potential to be employed for the analysis of CAs in biological fluids with preconcentration.;The third part of the dissertation focuses on the development of a nonradioactive neutralizer based on a corona discharge for electrospray aerosols used for capillary separations with CNLSD. The highly charged aerosol generated by electrospray must be neutralized to be sensitively detected by CNLSD. The conventional radioactive neutralizers have some disadvantages including special licensing and strict regulation, as well as periodic and costly replacement. A simple unipolar electrical neutralizer based on a corona discharge was developed for the charge neutralization application. The parameters affecting the corona discharge and neutralization process were studied and optimized. Compared to a CNLSD system using a radioactive neutralizer, the system with the electrical neutralizer showed higher signal and signal-to-noise ratio for test compounds, indicating better neutralization efficiency for the charged aerosol. Highly reproducible results were obtained with the robust and durable electrical neutralizer for both CLC- and CE-electrospray-CNLSD systems.