Evaluation of An Isochronic Study Design for Long-Term Frozen Stability Investigation of Drugs in Biological Matrices

Abstract

Long-term stability is a basic parameter in bioanalytical method validation; however, no criteria for conducting long-term stability studies are specified in current guidelines. We present an evaluation of a modified statistical approach applied to a study design utilizing an isochronic analysis (collection of samples to be analyzed at one time point) to determine the long-term stability and, further, a comparison with the most widely used continuous design. The presented approach has been used in regulated bioanalysis at Lundbeck for the past 7 years and has, in this period, been applied to 121 studies; all providing conclusive data. The isochronic approach eliminates day-to-day variation, reduces labor and adds to the flexibility in the laboratory. The statistical evaluation used is based on the relative difference between baseline samples and stability test samples as well as 90% confidence intervals for the mean concentration for each of the stability test points.