Identification and quantification of medical device extractables and leachables via non-target analysis (NTA); Analytical uncertainty.

Leachables are substances that are leached from a medical device during its clinical use and are important due to the patient health-related effects they may have. Thus, medical devices are profiled for leachables (and/or extractables as probable leachables) to assess their potential impact on patient health and safety. This profiling is accomplished by screening extracts or leachates of the medical device for released organic substances via non-targeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection. Chromatographic mass spectral response factors (RFs) for extractables and leachables vary significantly from compound to compound, complicating the quantitation of these compounds and the application of assessment strategies such as the Analytical Evaluation Threshold (AET). The analytical uncertainty resulting from response factor variation can be expressed in terms of an uncertainty factor (UF), which estimates the magnitude of response factor variation. This manuscript discusses the concept and impact of analytical uncertainty and provides best practice recommendations for the calculation and use of the uncertainty factor, UF.