Analytical chemistry applied to pharmaceuticals development: A study of drug product degradation and a study of the analysis of chiral pharmaceuticals.

摘要

Analytical chemistry plays a key role in the development, manufacturing and approval of pharmaceutical products. Pharmaceuticals are a highly regulated industry, consequently; two areas of analytical interest for Food and Drug Administration are analytical methods for compounded products and quantitation of enantiomeric purity of chiral drug substances.; Part I of this research focused on the evaluation of Benzamycin RTM, a compounded drug product. Compounded drug products, though evaluated, are not subjected to the level of scrutiny that is involved in traditional drugs. A danger of compounded products is that one does not know the final potency, which is based on the pharmacist mixing technique. The product was evaluated so as to determine the formulation. Research was mainly devoted to the development and validation of a stability indicating method for not only the active Benzoyl Peroxide, but also the related substances, benzoic acid, benzaldehyde and ethyl benzoate. The new combined rugged method was compared to compendial methods and found to be more accurate and sensitive. Predictions of degradation pathways were proposed. Forced degradation studies confirmed that the method was stability indicating.; Part II of the research was devoted to new methods for evaluating enantiomeric purity. It is known that enantiomers may have differences in biological efficacy and activity, thus it is imperative to know the quantities of each isomer present. The objective was to evaluate the purity of chiral drugs via a chiral separation method and a chiral detection method. Ketoprofen, Ibuprofen and Flurbiprofen were studied and a new reversed phase chiral HPLC method was developed. Additionally, circular dichroism was employed to evaluate purity. It has been concluded that not only are reversed phased chiral separation methods accurate, but also that an achiral method combined with circular dichroism detection can also evaluate purity. Enantiomeric excess values from CD detection were comparable to UV and fluorescence. Finally, it is recommended that the g-factor be used in determining chiral purity of drugs.; This research details some analytical barriers that pharmaceutical chemists encounter. Accomplishing theses goals exhibits success of new technologies and demonstrates the need to continually advance in analytical chemistry.