Chemical Characterization Solutions, LLC, PO Box 113, Newport, MN 55055, USA.
J Chromatogr A. 2022 Aug 2;1676:463240. doi: 10.1016/j.chroma.2022.463240. Epub 2022 Jun 17.
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.
用于生物相容性评估的脂肪组织接触医疗器械的化学特征化（即提取和浸出物测试，E&L）中使用的提取溶剂已被 Abraham 通用溶剂模型研究过。根据 Abraham 的有机溶剂系统系数，基于水和空气到冷凝有机溶剂相的溶剂化性质（溶解度、分配、提取等），提出了替代脂肪组织的化学合适溶剂。这种评估是基于 Abraham、Acree Jr 和 Cometto-Muñiz 的结论，即橄榄油在化学上与脂肪组织相对应。然而，如果橄榄油用作提取溶剂来模拟脂肪组织，根据 ISO 10993-18（2020），它在色谱分析方面通常不切实际（现实），因此寻找橄榄油的替代溶剂来进行提取至关重要。尽管烷烃等非极性溶剂已被提议并用作植物油的替代溶剂，但它们在溶剂化性质上与橄榄油并不等效。由于油样品的色谱分析存在实际挑战，以及 E&L 在油和有机溶剂之间的迁移动力学的差异，计算方法是评估橄榄油替代溶剂以模拟脂肪组织提取的唯一现实选择。通过比较 Abraham 溶剂系统系数，水和空气到冷凝有机溶剂相的分布，使用 Abraham 和 Martin 方程计算溶剂与橄榄油之间的五维空间距离（D），以预测橄榄油的替代或相似溶剂。进一步根据溶剂与橄榄油之间的 E&L 溶解度比，考虑溶剂安全性和物理性质，对计算结果进行评估。研究得出的结论是，丁酮和二恶烷是化学上最适合替代或代表橄榄油的溶剂。它们可以用作医疗器械化学特征化研究中的脂肪组织代表性溶剂。由于 Abraham 溶剂模型是特定溶剂系统的，而不是特定溶质的，因此本研究的结论被认为是普遍适用的。
