Thermodynamic Insights into Organic Solvent Extraction for Chemical Analysis of Medical Devices

Jianwei Li of Chemical Characterization Solutions in Newport, Minnesota recently developed a new approach for sample preparation in chemical characterization of medical devices. His findings were published in the Journal of Chromatography Open (1).

Modern equipment in operating room. Medical devices for neurosurgery. | Image Credit: © romaset- stock.adobe.com

Chemical characterization is when analytical chemistry is used to identify and quantify any chemical species that can potentially leach from a medical device, which can cause direct or indirect human exposure from the use of medical devices. The chemical characterization of medical devices (or assessment of extractables and leachables [E&L]) is an essential aspect of the regulatory review and approval of medical devices in the United States, the European Union (EU), and most major markets around the world (2). The liquid–solid (L–S) extraction of medical devices, including their components or materials, using appropriate extraction solvents or conditions is the first sample preparation step in chemical characterization studies. This is followed by instrumental analysis of extraction samples (also known as extracts) to determine the concentration of E&L chemical entities, which are then used for toxicological risk (or safety) assessments.

Two major types of extraction studies are typically performed in chemical characterization of medical devices, with exaggerated and exhaustive extractions depending on the nature and duration of device-patient contacts. Exaggerated extraction is a laboratory procedure that uses conditions to release more extractables from a device than would be released under normal use conditions. Meanwhile, an exhaustive extraction is conducted by using solvents (water, ethanol, and hexane) of different polarity (and temperature), intended to enable the release of diverse classes of chemicals in a wide range of physicochemical properties, possibly existed in device materials.

In this study, the Abraham’s model was used to predict the material-solvent partition system coefficients by the corresponding partition system constant and representative extractables. The Abraham’s solvation parameter model is used to model and predict distribution properties of compounds in numerous partitioning systems in various scientific fields (3). Partition system constants are indirectly derived by a “thermodynamic circle conversion” method, based on material-water partition systems and solvent-water partition systems or material-air partition systems and solvent-air water partition systems. The material-solvent partition coefficient (P_M/Solvent= C_M/C_Solvent) is defined as the concentration in the material phase divided by the concentration in the solvent phase and is used as the solvent extraction strength. Log(P_M/Solvent) values were predicted for all material-solvent pairs using representative extractables, mostly from the Wayne State University experimental descriptor database (WSUEDD). This database was created “utilizing gas and reversed-phase liquid chromatography retention factors and liquid-liquid partition constants determined in a single laboratory” (4). With this data, scientists can control the experimental techniques used alongside selection tools to identify systems that will likely cause unreliable experimental values for certain compounds. The predictive log(P_M/Solvent) values of material-solvent pairs are considered as the upper bound, indicating the significance of partitioning effect in solvent extraction. The calculation results using water-based or air-based partition systems were also compared, and the predictive results were discussed in relation to the solvent-material interaction or swelling.

The predictive consistency was established for two conversion systems: water-based or air-based. These indicated the accuracy and robustness of Abraham’s model. Secondly, the predicted partition coefficients were confirmed through available experimental values, with the predicted solvent extraction strengths being supported by available experimental extraction data. The kinetic effect also proved the dominant extractables release process in sample preparation for chemical characterization studies. Acetone and butanone could also be the general-purpose solvent for extracting materials, eliminating the need for three solvents in chemical characterization studies. Finally, the Abraham’s solvation parameter model was deemed invaluable for understanding and differentiating solvent extraction processes.

References

(1) Li, J. Evaluation of Thermodynamic Contributions to Extraction of Medical Devices by Organic Solvents as a Sample Preparation Step in Chemical Characterization of Medical Devices. J. Chromatogr. Open 2025, 7, 100199. DOI: 10.1016/j.jcoa.2024.100199

(2) Reeve, L.; Baldrick, P. Biocompatibility Assessments for Medical Devices – Evolving Regulatory Considerations. Expert Rev. Med. Devices 2017, 14 (2), 161–167. DOI: 10.1080/17434440.2017.1280392

(3) Li, J. Application of Abraham's Solvation Parameter Model to Extractables and Leachables Studies in Pharmaceutical and Medical Device Industries: A Tutorial. J. Chromatogr. Open 2024, 6, 100158. DOI: 10.1016/j.jcoa.2024.100199

(4) Poole, C. F. Wayne State University Experimental Descriptor Database for Use with the Solvation Parameter Model. J. Chromatogr. A 2020, 1617, 460841. DOI: 10.1016/j.chroma.2019.460841