Solvent effects on AIBN and ACVA oxidative forced degradation profiles

ANYL 68

Holly Marie Kerwin, Holly_Kerwin@Merck.com1, Eric D. Nelson1, Gina M. Thompson1, and Paul A. Harmon2. (1) Pharmaceutical Analytical Sciences and Quality Testing, Merck Manufacturing Division, 770 Sumneytown Pike PO Box 4, WP78A-31, West Point, PA 19486, (2) Pharmaceutical Analytical Chemistry, Merck Research Laboratories, West Point, PA 19486
Purpose: This presentation explores the effects of solvent type and composition on the kinetics and product distributions of AIBN and ACVA-initiated oxidative forced degradation of a drug molecule of known degradation chemistry.

Methods: The kinetics of drug degradation were measured by sequential injection of stress samples on an Agilent 1100 HPLC system with sample tray controlled at 40°C to induce initiator decomposition.

Results: The kinetics and product distributions of AIBN forced degradation depend significantly on solvent composition. For example, even small amounts of water have a marked impact on the kinetics of degradation in acetonitrile. ACVA is found to be significantly less sensitive to solvent composition. Acetonitrile shows a significant increase in the speed of the reactions over other solvents explored such as methanol and iso-propanol. Although the rate at which the reactions occur vary greatly in the different solvent systems, the primary degradate remains consistent and there is significant overlap in the distribution of minor degradates.

Conclusions: Solvent choice and composition are important variables in the azonitrile-initiated forced degradation experiment. Even low moisture levels in acetonitrile lead to a significant decrease in AIBN-induced degradation rates. The implications of the solvent effects are discussed.

 

General Papers
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Analytical Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006