Extractables or leachables of biomaterials or residues of additives used in the manufacturing process that are potentially released from a medical device may have an adverse effect on a patient. Chemical characterization of leachable chemicals and degradation products in a medical device is an important aspect of its overall biocompatibility assessment process, which helps to ensure that the therapeutical benefits exceed the potential biological risks associated with the use of the device or its components or materials. By evaluating the types and amounts of chemicals that may migrate from a device to a patient during clinical use, potential toxicological risks can be assessed. A semipolar solvent, 40% ethanol in water (v/v), an appropriate surrogate for blood and blood related substances, was used as an extraction medium to mimic the body fluid in contact with a medical device. The extraction was conducted at 37 °C for 24 h for limited exposure medical devices per ISO 10993-12:2021. From gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) analysis, leachable chemicals of polylactams, linear polyamides, cyclic polytetramethylene ether (PTME), poly­(tetramethylene ether) glycol (PTMEG), cyclic and linear poly­(tetramethylene ether) glycol adipate (PTMEGA), cyclic and linear poly­(tetramethylene ether) glycol adipamide (PTMEGAA) were structurally elucidated. The workflow presented in this study was proven to be a successful approach for rapid extractable and leachable profiling and identification with confidence.

The chemical characterization of extractables and leachables (E&Ls) is an important aspect of biosafety and biocompatibility assessment in medical device industry. The advent of the body-contact use of medical devices in patient treatment has introduced a potential source for extractables and leachables as these medical devices are comprised of various polymeric materials. Several industry working groups, the FDA and USP, have recognized the guidance for chemical characterizations and nontargeted analysis of medical device extracts, such as ISO 10993–18:2020. The MS application of nontargeted analysis has played a critical role in understanding the E&Ls from medical device extracts. However, there have been very few reports about the MS based workflow with nontargeted analysis for medical device extracts and there is little guidance about the exact methodologies which should be used, even though there is an urgent need for a clearly defined process for the identification of medical device extracts. In this study, we demonstrated an analytical LC/MS (liquid chromatography/mass spectrometry) workflow using high resolution Exploris120 Orbitrap instrument for data acquisition and Compound Discoverer 3.3 intelligent software for data processing to profile the polymer related E&Ls from a balloon dilation catheter device extracted with 40% ethanol. An E&L ID workflow combining LC separation, data-informed MS acquisition strategy, MS information mining (including adduct ions, MS information from both electrospray ionization (ESI) (+) and ESI (−), in-source fragmentation, common fragment ions (CFIs), common neutral losses (CNLs), and in silico MS simulation was described with intelligent software processing and manual data interpretation. The workflow developed in this study was proven to be effective to provide a comprehensive profile of polymer related degradation products, polymer impurities and additives including surfactants, UV curing agent, antioxidants, and plasticizers for the device analyzed. The classification of E&L compounds using CFIs and CNLs was very effective to facilitate the identification of polymer related impurities and extract the polymer related impurities with common structures in a large data result set.