The development of separation methods for the analysis of pharmaceuticals in environmental and biological samples

This dissertation describes the development of separation methods coupled to both UV and mass spectrometric detection for the analysis of pharmaceuticals in complex matrices. Applications of the developed method were environmental and biological.; The detection of pharmaceuticals in environmental samples from Lawrence, KS, was investigated. CE/MS/MS and LC/MS/MS methods were developed in order to detect multiple compounds in the samples. A solid phase extraction method was also optimized to clean up and concentrate the environmental samples. Samples were collected from the influent and effluent of the Lawrence, KS, wastewater treatment plant and the Kansas River at two separate locations. Four out of five acidic pharmaceuticals were identified and quantified in the influent and effluent. Two out of five acidic pharmaceuticals were detected and quantified in the river water.; An amiodarone prodrug was provided by ProQuest Pharmaceuticals, Inc. (Lawrence, KS) for in vitro and in vivo characterization studies. The prodrug was developed to improve the delivery attributes of amiodarone for intravenous dosing. A separation method for the prodrug and amiodarone was developed using LC/UV and studies conducted in vitro assessed the purity of several prodrug batches. The stability of the prodrug was measured in several matrices and the conversion of prodrug to amiodarone was confirmed. The studies conducted in vivo monitored the prodrug and amiodarone concentration over time, in Sprague-Dawley rats dosed with the prodrug. These experiments established pharmacokinetics parameters of the prodrug and were compared to the pharmacokinetics parameters of amiodarone. The distribution of amiodarone in tissue from a prodrug dose was also measured in rats using microdialysis sampling. Amiodarone was detected in the tissues at low concentrations.