Exploring three-dimensional space of extractables and leachables in volatility, hydrophobicity, and molecular weight and assessment of roles of gas and liquid chromatographic methods in their comprehensive analysis

Abstract

The three-dimensional (3D) global space of organic extractables and leachables (E&L) in volatility, hydrophobicity, and molecular weight (MW), covering the pharmaceutical container-closure system, biopharmaceutical single use equipment, and tissue-contacting medical devices, has been quantitatively explored by an extensive collection of E&L compounds from the publicly available sources. The total number of compounds collected is 776, including name, CAS number, MW, and boiling point (BP). The hydrophobicity of these compounds in logPo/w are computed by Abraham solvation parameter model, using compounds’ descriptors generated by an online computational program “RMG: Solvation Tools”. A “global” 3D space is built to represent the physicochemical property limits of E&L quantitatively, envisioned to cover a variety of materials extracted by different solvents. This 3D space also represents the scope and capability requirements of general-purpose chromatography-based methods to profile unknown material samples, if a limited number of analytical methods are used in a routine laboratory analysis. It is concluded from the study that the 3D space corresponding to MW of 1000 Da are: BP up to 857 °C and hydrophobicity in logPo/w between − 2.3–19. Additionally, the roles of temperature programmed GC (TPGC) and reversed-phase liquid chromatographic (RPLC) methods are quantitively and critically examined in the comprehensive analysis of the 3D space, particularly for RPLC methods in retention and resolution requirements, and it is also concluded that the current concept of analytical E&L testing strategies based on volatility needs to be challenged. Finally, this study proposes a semi-empirical method in correlation and prediction of the retention time of TPGC using Abraham solvation parameter model.