Chromatography

Drug eluting stents (DES) have become a standard of care for the treatment of symptomatic atherosclerotic coronary artery

disease. DES combine drug and device components, and are therefore combination products within the meaning of

section 503(g) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. § 353(g). Analytical methods used in drug eluting stents

analysis must be suffi ciently accurate, specifi c, sensitive and precise to ensure quality and reliability of the results, which in

turn are crucial for ensuring the quality, stability, safety and effi ciency of DES. Th ere are numerous challenges to overcome

when developing analytical methods for the DES products. Th e low levels of the active substance(s) loaded on the DES and

their poor water solubility, low levels of other analytes of interest (residual solvent, monomer content, lactic acid, oligomers,

and antioxidants) and the presence of polymer(s) in the sample matrix make the selection of sample pretreatment, detection

mode and the development of separation conditions extremely diffi cult. Limited guidance is available on how to achieve an

appropriate consideration of the analytical variability in analytical methods used to monitor the quality of the DES products

over the shelf-life and set the appropriate method validation acceptance criteria to maintain the method capability and

demonstrate its suitability for the intended purpose.