title: 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.
authors.affiliation: Department of Bioanalysis, Drug Development ADME, H Lundbeck A/S Ottiliavej 7-9, DK-2500 Valby-Copenhagen, Denmark. supi@lundbeck.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Pihl
authors.forename: Anna Karina Trap
authors.initials: AK
authors.lastname: Huusom
authors.forename: Morten
authors.initials: M
authors.lastname: Rohde
authors.forename: Mette Nøhr
authors.initials: MN
authors.lastname: Poulsen
authors.forename: Martin
authors.initials: M
authors.lastname: Jørgensen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Kall
mesh_terms: D000818:Animals; D004285:Dogs; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D051379:Mice; D004364:Pharmaceutical Preparations / Q000097:blood; D011817:Rabbits; D051381:Rats; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations