Date of Award

7-24-2008

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dennis M. Gross, M.S., PhD

Second Advisor

Dana Bragg

Third Advisor

Ponniah Shenbagamurthi, PhD

Fourth Advisor

R. John Stubbs, PhD

Fifth Advisor

David Thomas, M.S.

Abstract

HPLC is a commonly used analytical tool in the pharmaceutical industry for the characterization of drug potency and purity. However, HPLC analysis can be very time consuming, use large quantities of organics, and thus costly and not environmentally friendly. In this study, we describe an alternative to HPLC that can be used for pharmaceutical analysis. Capillary electrophoresis is being utilized increasingly for biochemistry and analytical chemistry applications. With advances in auto samplers and improvements in injection precision, the potential for this instrumentation to be used in conjunction or as an alternative to HPLC is currently being evaluated in analytical laboratories. Capillary electrophoresis allows for minimal organic consumption, fast analysis time, and high degree of resolution. In addition, capillary electrophoresis assays are more cost effective to develop and run on a routine basis due to relatively less expensive capillaries and small amounts of organic solvents. In this study, capillary electrophoresis is used for analysis of 3 classes of antifungal compounds; an imidazole, polyene and a pyrimidine, represented by miconazole, nystatin and 5-fluorocytosine. Utilizing USP validation criteria, we find comparable levels of accuracy, limit of detection (LOD), limit of quantification (LOQ), linearity, and precision to HPLC. Using, a 40 cm x 75 μm capillary with a KH2P04 run buffer for both miconazole and 5-fluorocytosine, we show that both agents can be captured in less than 3 minutes with a RSD < 2.0, and a linearity R2 > 0.99. For nystatin, there were solution solubility issues due to the organic: aqueous ratio and further investigation is needed to determine if comparable data to HPLC can be obtained.

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