Leachables present in packaged drug products or released from medical devices can adversely affect patient health and safety. Thus, packaged drug products are screened for unspecified leachables, and packaging system or medical device extracts are screened for unspecified extractables as potential leachables, a process known as non-targeted analysis (NTA). Screening methods for organic extractables and leachables typically employ chromatography to separate analytes and information-rich detectors [such as mass spectrometry (MS)] to detect, identify, and quantify them.
Chromatographic screening methods are generally qualified to establish that they are suitable for their intended use. When the qualified methods are implemented during extractables and leachables studies, system suitability testing is conducted during each chromatographic run to ensure that the method performs properly at the time of use.
System suitability testing in extractables and leachables screening requires a standard mixture of relevant compounds that themselves are extractables and leachables. To facilitate consistent analytical performance across laboratories and to standardize system suitability testing, a standardized system suitability mixture (meaning a mixture with specified constituents), used by all practitioners, is necessary.
Based on several scientific and practical considerations, USP is developing a set of system suitability reference standards for the most commonly employed hyphenated chromatographic screening methods, such as gas and liquid chromatography with mass spectrometric detection (GC/MS and LC/MS). In this article, the USP approach to reference mixture development is discussed; the compositions of the reference standard mixtures are disclosed, discussed, and justified; and typical chromatograms are provided. USP is seeking feedback from stakeholders on the proposed mixtures. The article also discusses other opportunities for development of reference standards and reference standard mixtures to support extractables and leachables testing (e.g., calibration mixtures, individual reference standards for “hard-to-find” extractables, and leachables, etc.).