Controlling the Structure of a Trifluoroacylated Hydrazino Pharmaceutical Intermediate for Improved HPLC and GC Analyses

Abstract

A process to generate an organofluorine pharmaceutical intermediate yields two main products, a bis‐ and mono‐trifluoroacylated analog of the hydrazino starting material. Analytical methods are discussed that characterize solid and solution intermediate mixtures, as well as monitor their formation. In addition, quantitative high performance liquid chromatography (HPLC) assay method development and validation is presented. However, due to solution stability issues, a diluent system that forcibly, yet controllably, degraded the bis‐trifluoroacylated product to the mono analog had to be employed. A more in depth discussion of the investigation into the appropriate diluent system is also presented.

Keywords:

• HPLC
• Controlled degradation
• Organofluorine analysis
• Pharmaceutical analysis

Acknowledgments

The authors would like to thank Dr. Dietrich Steinhuebel and Dr. Michael Palucki of the Process Research & Development Department of MRL for supplying all of the trifluoroacylated intermediates used in this investigation.