Evaluation of fatty tissue representative solvents in extraction of medical devices for chromatographic analysis of devices' extractables and leachables based on Abraham general solvation model.

Extraction solvents used in chemical characterization (i.e., extractables and leachables testing, E&L) of fatty tissue-contacting medical devices for biocompatibility assessment per ISO 10993 have been studied by Abraham general solvation models. Chemically suitable alternative solvents to fatty tissues in solvation properties (solubility, partition, extraction, etc.) have been proposed based on Abraham's organic solvent system coefficients for water and air to condensed organic solvent phases. This evaluation is built upon the conclusion by Abraham, Acree Jr and Cometto-Muñiz that olive oil is chemically corresponding to fatty tissues. However, olive oil, if used as an extraction solvent to simulate fatty tissues, is in general not analytically expedient (realistic) per ISO 10993-18 (2020) for chromatographic analysis, and it is critical to seek alternative solvents to olive oil to perform the extraction. Although nonpolar solvents such as alkanes have been proposed and used as alternative solvents to vegetable oils, they are not equivalent to olive oil in solvation properties. Due to the practical challenge in chromatographic analysis of oil samples and the difference in migration kinetics of E&L between oil and organic solvents, the computational approach is the only realistic option to evaluate chemically alternative solvents to olive oil to simulate fatty tissue extraction. By comparing Abraham solvent system coefficients for water and air to condensed organic solvent phases distribution, a five-dimensional space distance (D) between solvents and olive oil as a reference solvent is calculated using Abraham and Martin equation to predict alternative or similar solvents to olive oil. The results of the calculation are further evaluated using E&L solubility ratio between solvents and olive oil, taking into consideration of solvent safety and physical properties. It is concluded from the study that butanone and dioxane are chemically the most suitable alternative or representative solvents to olive oil. They can be used as fatty tissue representative solvents in chemical characterization study of medical device. As Abraham solvation model is solvent system specific, not solute specific, the conclusions from this study are considered as universal.