| Efforts toward the development of methods to separate, detect, and quantitate pharmaceutical compounds and biological analytes in complex matrices using liquid chromatography-tandem mass spectrometry (LC/MS/MS) are described. The research discussed herein covers environmental, bioanalytical, and metabonomic applications.; The goal of the environmental application was to determine pharmaceutical compound concentrations in sewage, river, and tap water following concentration and cleanup using solid phase extraction (SPE) and LC/MS/MS. Five basic pharmaceuticals and two neutral pharmaceuticals were confirmed to be present in the environmental samples using a LC/MS/MS product ion scan. The concentrations of the pharmaceuticals were determined using a multiple reaction monitoring (MRM) analysis and a deuterated internal standard.; The bioanalytical application objectives were two fold: (i) to monitor the skin penetration of EsteromRTM components using dermal microdialysis and LC/MS/MS MRM analysis, (ii) to detect metabolites collected by intravenous microdialysis in a rat using an LC/MS/MS MRM analysis, after a subcutaneous dose of one EsteromRTM component (an esterified metabolite of cocaine) thought to possess anesthetic properties. The topically applied components of EsteromRTM were found to penetrate at low concentrations and a large variation in penetrating concentrations was observed. After a subcutaneous dose of the target analyte, systemic exposure to the dosed compound and further metabolites was observed.; The purpose of the metabonomic-based investigation was to develop a screening method for determining nucleosides and modified nucleosides in urine SPE extracts using an LC/MS/MS neutral loss scan. Urine from a male smoker and a male non-smoker were subjected to SPE and the extracts were analyzed to demonstrate the utility of this screening method. |
