Evaluation of blood simulating solvents in extractables and leachables testing for chemical characterization of medical devices based on Abraham general solvation model

Abstract

Extraction vehicles (simulating solvents) used in chemical characterization (i.e., extractables/leachables testing) of blood-contacting medical devices for biocompatibility assessment per ISO 10993 have been studied by Abraham general solvation models. Chemically equivalent solvents to blood 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 water saturated n-butanol (called wet n-butanol) is chemically corresponding to blood. Although wet n-butanol can be directly used to replace blood in an extraction study (such as a simulated-use extraction study per ISO 10993-18 (2020)), it can be beneficial to have alternate solvents to wet n-butanol (butan-1-ol) when chromatographic interference is practically significant. By comparing Abraham solvent system coefficients for water to condensed organic solvent phases distribution, a five-dimensional space distance (D) between solvents and reference solvent (wet n-butanol) is calculated using Abraham and Martin equation to predict equivalent or similar solvents (to wet n-butanol). It is concluded from the study that ethanol/water (60/40, V/V) and ethanol/water (50/50, V/V) are chemically equivalent or quite similar to wet n-Butanol. Other two less similar solvents are ethylene glycol and ethanol/water (70/30, V/V). Thus, n-butanol, ethanol/water (60/40, V/V) and ethanol/water (50/50, V/V) can be used as blood simulating solvents in chemical characterization study of medical device. In certain situations, ethylene glycol might be desirable as an alternate solvent, as it is not a mixture. As Abraham solvation model is general (solvent system specific, not solute specific), the conclusions from this study are considered as universal.