Chemical Characterization of Leachables in Catheter Device

Abstract

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.

A Chemical Characterization Workflow for Nontargeted Analysis of Complex Extracts from Polymer Based Medical Device Using High Resolution LC/MS

“…Some of the compounds listed in Table 2 have been reported from a previous paper focusing on the chemical characterization of PEBAX related medical device extracts. 17 In this paper, additional E&L components including dodecyl sulfate, myristyl sulfate, bis(4ethylbenzylidene) sorbitol, tributyl citrate, and N-butylbenzenesulfonamide were identified with mzCloud Database Searching and listed in Table 2. These compounds were used as polymer additives (plasticizers and surfactants).…”

“…Additional Pebax related polymer degradation products were identified as HO(CO-(CH 2 ) 11 -NH) x -CO-(CH 2 ) 4 -CO-O(CH 2 CH 2 CH 2 CH 2 O) y -H or cyclic -(CO-(CH 2 ) 11 -NH) x -CO-(CH 2 ) 4 -CO-O(CH 2 CH 2 CH 2 CH 2 O) y - compounds ( x = 0, 1, 2; y = 0–10) using this MS simulation workflow. These identified compounds were in agreement with the previous report from this laboratory …”

“…A lot of laurolactam related impurities were also identified based on MS information mining, retention time alignment, MS/MS data confirmation and MS simulation. Some of the compounds listed in Table have been reported from a previous paper focusing on the chemical characterization of PEBAX related medical device extracts . In this paper, additional E&L components including dodecyl sulfate, myristyl sulfate, bis­(4-ethylbenzylidene) sorbitol, tributyl citrate, and N -butylbenzenesulfonamide were identified with mzCloud Database Searching and listed in Table .…”

“…Its in silico MS/MS fragmentation algorithms (Mass Frontier) and FISh (Fragment Ion Search) can be used for unknown identifications with the proposed structures of unknowns and the structures from compound databases such as Chemspider and Pubchem. In a previous publication, 17 several classes of PEBAX related polymer extractable and leachable chemicals were identified and reported from this laboratory. Here, using a medical device product that contains similar PEBAX materials as a model testing article, a more detailed description and discussions are provided on a very effective LC/MS analysis workflow.…”