| Although current drug separation and detection methods are reliable and quantitative, the sample preparation time and analysis times are lengthy. Due to the increased need for drug testing of biological samples, decreases in the analysis times by reducing both the sample preparation and separation are required. Due to the rapid separation times (milliseconds) in IMS, the feasibility of employing electrospray ionization (ESI)/ion mobility spectrometry (IMS)/mass spectrometry (MS) for the direct analysis of biological samples was investigated. The separation of three important drug classes was shown; opiates, benzodiazepines, and amphetamines. Many of the drugs contained hydroxyl groups and were susceptible to the loss of water. The mechanisms by which this loss occurs were investigated with the benzodiazepines and the structural changes were studied with the opiates. Since selectivity of ions in IMS can be altered by changing the drift gas, a database of reduced mobility values for fifteen common drugs and metabolites was assimilated in several drift gases.; Unlike chromatographic separation techniques, the ionization of the analytes occurs prior to the IMS separation. Thus, in order to understand the ion intensities observed and possible matrix effects from biological samples, it was important to understand ESI mechanisms and components that influence the ion signal intensity. Based on ESI/MS literature, it was known that there were two phenomena that affect ion intensity: (1) charge competition and (2) ion suppression. Charge competition processes and different ESI solutions were studied with amphetamines as test compounds. The changes in charge competition were fit to models for comparison with ESI mechanism theory. The effect of salts was studied with commonly used liquid chromatography buffers. They were found to invoke ion suppression at mM concentrations. Micro-spray conditions were studied as a solution to ion suppression and were found to provide some improvement in ion intensity. The ionization studies described above showed that ESI/IMS could be employed for biological samples where the major matrix components were well characterized. |
