A novel approach for the bioanalysis of short-lived aldehydes

Background: The instability of aldehydes in biological matrices is associated with their reactions with thiol and amino moieties in proteins. This chemical reaction is reversible by nature and highly pH dependent. Method: A novel approach that includes protein precipitation with an acidic solution of acetonitrile/water/formic acid (85/14/1; v/v/v) was developed to efficiently recover Aldehyde-1 from plasma by shifting the equilibrium toward the formation of the free form. Results: This enabled the support of two GLP studies where Aldehyde-1 was administered to mice. The recovery of Aldehyde-1 from plasma exceeded 88% at three concentration levels. Plasma stability was confirmed at ambient conditions for 24 h and in the freezer for at least 43 (-20°C) and 64 (-70°C) days.