Stir bar sorptive extraction combined with GC–MS/MS for determination of low level leachable components from implantable medical devices

Identification and determination of leachable components are essential for the safety assessment of implantable medical devices. The safety concern threshold (SCT) for leachable components is 0.15 μg/day for genotoxic or carcinogenic compounds and 1.5 μg/day for others. Regulatory agencies require extraction of a whole medical device using an extraction media that simulates in vitro conditions. Large-sized medical devices therefore require large volumes of aqueous media, leading to extracts of very low concentrations of the targeted analytes. Analysis of these dilute solutions is often challenging, and pre-concentration steps are time consuming and can cause significant sample loss. Stir bar sorptive extraction (SBSE) has proven to be a very useful sample preparation technique that is simple and uses no (or minimal (<1 ml)) aqueous or organic solvents. When combined with a highly selective and sensitive GC–MS/MS analysis, volatile and semi-volatile leachable components can be determined at levels below the SCT of 150 ng/device. An SBSE–GC–MS/MS method using multiple reaction monitoring detection was validated for determination of antioxidant related leachable breakdown products from orthopedic knee-inserts made from ultra high molecular weight polyethylene.

► SBSE based extraction method developed to evaluate leachables from medical devices.
► Method was validated as a limit test according to ICH guideline using GC–MS/MS.
► Detection limits achieved of less than 500 pg/device for GC–MS/MS.
► Validation was designed and executed to comply with 2002/657 EU Council Directive.