Analytical method development a mathematical approach

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Katherin M. Schlipp (Creator)
The University of North Carolina Wilmington (UNCW )
Web Site:
Dean Shirazi

Abstract: Drug development relies strongly on the construction of optimal analytical methods in an abbreviated timeframe in order to identify a final formulation and get to market quickly. Simplification of the analytical development process for multiple active products potentially provides a company with higher revenue as well as general cost reductions. This research strongly demonstrates the benefits of using systematic and mathematical approaches when developing analytical methods for a complex mixture. By performing two gradient runs having different gradient slopes, and using a mathematical relationship between retention times of each solute for each gradient and each solute’s characteristic values, sj and k’j,w, the optimum gradient method for the separation of diclofenac, propoxyphene, and their respective impurities was developed. The method was further optimized by adjustment of the pH. Using a mixture design approach, an isocratic method for a ternary system was developed for the aforementioned separation, which required three experiments to find the optimum mobile phase composition. A binary system for an isocratic separation was also developed. Development of this method was optimized by investigating the variations of characteristic values of each solute as a function of column temperature. Additionally, a dissolution method was designed to mimic the release of diclofenac and propoxyphene once the drug product is ingested into the human body. A rapid isocratic HPLC method was developed for the determination of the amount of diclofenac and propoxyphene that is dissolved in dissolution samples.

Additional Information

A Thesis Submitted to the University of North Carolina at Wilmington in Partial Fulfillment Of the Requirements for the Degree of Master of Science
Language: English
Date: 2009
Drug design, Drug development--Methodology, Liquid chromatography
Drug development -- Methodology
Drug design
Liquid chromatography

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