An HPLC chromatographic reactor approach for investigating the hydrolytic stability of a pharmaceutical compound

ANYL 65

Peter J. Skrdla, peter_skrdla@merck.com, Analytical Development & Commercialization, Merck & Co., Inc, P. O. Box 2000, RY818-C214, Rahway, NJ 07065, Yan Wu, yan_wu@merck.com, Analytical Reasearch Department, Merck & Co., Inc, P.O. Box 2000, RY80Y-335, Rahway, NJ 07065, and Ahmed Abrahim, Analytical Research, Merck & Co., Inc, PO Box 2000, 818-B218, Rahway, NJ 07065.
The solution-phase hydrolysis kinetics of the prodrug, Fosaprepitant Dimeglumine (FD), were investigated using an HPLC chromatographic reactor approach. The term ‘chromatographic reactor' refers to the use of an analytical-scale column as both a flow-through reactor and, simultaneously, as separation medium for the reactant(s) and product(s). It is found that the hydrolysis of FD has an apparent activation energy of 107 kJ/mol when the reaction is investigated on-column. For comparison, the activation energy determined for the same reaction occurring in a quiescent solution consisting of a fixed ratio of acetonitrile and 0.1% v/v aqueous H3PO4 (50:50, v/v) is 91 kJ/mol, calculated using direct application of the Arrhenius equation. The data presented show that, when used as a screening tool, chromatographic reactors may be feasible for use in the pharmaceutical industry to quickly gauge the relative stabilities of various compounds with similar degradation pathways.
 

General Posters
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Analytical Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007