Robustness of an Immobilized Artificial Membrane High-Performance Liquid Chromatography Method for the Determination of Lipophilicity

Hydrophobicity is an intrinsic property that relates to a chemical’s tendency to partition between a polar and a nonpolar phase. Traditionally, hydrophobicity has been described by the logarithm of the octanol–water partition coefficient (log <i>K</i>_OW or log <i>P</i>). Immobilized artificial membrane high-performance liquid chromatography (IAM-HPLC) is an alternative method to determine hydrophobicity that may be more biologically relevant. This paper examines the robustness of an IAM-HPLC assay optimized using the IAM.PC.DD2 column to determine the retention factor (log <i>k</i>_{IAM (pH 7.4)}). The method has been shown to be robust following robustness testing of five compounds (log <i>K</i>_OW ranging from 0.29 to 6.03) assessed across five columns (which included three batches of stationary phase) and two HPLC systems

Construction of an In Silico Structural Profiling Tool Facilitating Mechanistically Grounded Classification of Aquatic Toxicants

The performance of chemical safety assessment within the domain of environmental toxicology is often impeded by a shortfall of appropriate experimental data describing potential hazards across the many compounds in regular industrial use. In silico schemes for assigning aquatic-relevant modes or mechanisms of toxic action to substances, based solely on consideration of chemical structure, have seen widespread employmentincluding those of Verhaar, Russom, and later Bauer (MechoA). Recently, development of a further system was reported by Sapounidou, which, in common with MechoA, seeks to ground its classifications in understanding and appreciation of molecular initiating events. Until now, this Sapounidou scheme has not seen implementation as a tool for practical screening use. Accordingly, the primary purpose of this study was to create such a resourcein the form of a computational workflow. This exercise was facilitated through the formulation of 183 structural alerts/rules describing molecular features associated with narcosis, chemical reactivity, and specific mechanisms of action. Output was subsequently compared relative to that of the three aforementioned alternative systems to identify strengths and shortcomings as regards coverage of chemical space