Part I. Supercritical fluid extraction and liquid chromatography-electrospray mass spectrometry of selected drugs of abuse from various biological matrices. Part II. HPLC determination of selected drugs using smallbore and nonporous octadecylsilane columns.

摘要

The scope of the research of in this dissertation encompasses two sections: the use of supercritical fluid extraction and liquid chromatography-mass spectrometry in the analysis of various model drugs and the analysis of selected pharmaceuticals using smallbore and nonporous octadecylsilane columns.;In Chapter I, the extraction, separation and quantitation of several commonly used barbiturates from human serum is described using supercritical fluid extraction (SFE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Correlation coefficients were ;In Chapter II, a novel SFE method with subsequent LC-MS analysis is described for cocaine and 13 of its metabolites from meconium. Correlation coefficients ranged from 0.9634 to 0.9999. RSDs ranged from 0.2 to 29.1%. Accuracy, precision, and coefficients of variation are described for the method.;In Chapter III, a stability indicating HPLC-diode array method for the analysis of clonazepam from a tablet dosage form using a smallbore (3.0 mm i.d.), octadecylsilane HPLC column is presented. Standard degradation conditions were applied to clonazepam. The analysis was conducted with and without an internal standard, and other column types are presented. The method was compared to the current USP 23 method for the analysis of clonazepam in a tablet dosage form. The intra- and interday RSDs on the 3.0 mm i.d. column were less than 0.55% (n = 4) using the internal standard, and less than 0.19% (n = 4) without the internal standard at the lower limit of the standard curve, 50 ug/ml and had a limit of detection of 24 ng/ml.;In Chapter IV, a method to quantitate aspirin, caffeine, and codeine using a novel nonporous octadecylsilane HPLC column was developed using UV detection. The method has shown a significant decrease in analysis time, making it amenable to high throughput. The mass transfer characteristics of this new column are superior to conventional 3.9 or 4.0 mm i.d. columns, making their efficiencies better. The method was compared to the current USP 23 method for this analgesic mixture and chromatographic figures of merit are presented. Inter- and intraday precision ranged from 0.12-1.95% for aspirin, 0.07-1.69% for caffeine, and 0.06-1.69% for codeine. The limits of detection for the analytes were 157 ng/ml for aspirin, 28 ng/ml for caffeine, and 30 ng/ml for codeine based on a signal-to-noise ratio (S/N) of 3 and a 10 microliter injection.;In Chapter V, meropenum, a new generation antibiotic, and ofloxacin, were analyzed by HPLC-UV using a nonporous octadecylsilane HPLC column from common IV injection solutions. The method was shown to be stability indicating by subjecting both analytes to the standard degradation conditions of acid, base, heat, peroxide, and light. In all cases, the degradation products did not interfere with the analytes of interest. The method was shown to have a very short analysis time and solvent waste was reduced. Standard curves were prepared and correlation coefficients were