Comparative evaluation of three high‐performance liquid chromatography–based K_ow estimation methods for highly hydrophobic organic compounds: Polybrominated diphenyl ethers and hexabromocyclododecane

Abstract

Three methods for estimating the octanol-water partition coefficient (Kow) based on its relationship with capacity factors on reversed-phase (RP) high-performance liquid chromatography (HPLC) columns were compared in terms of their applicability to highly hydrophobic compounds (HHCs). Methods based on simple isocratic elutions were found to be unsuitable, because the very high organic modifier fractions that are required to elute HHCs from RP columns challenge the basic assumption of the similarity between the octanol-water and RP-eluent systems. Compound planarity was found to exert a considerable influence on the retention of HHCs in RP columns, leading to different linear calibration curves for chlorobenzenes and chlorobiphenyls. Only an empirical exponential regression succeeded in describing the behavior of both groups of compounds during gradient elutions. In a method based on isocratic retention times at multiple temperatures, satisfactory calibration was achieved with a multivariate linear regression that included a numerical indicator of compound planarity. Considering experimental simplicity, speed, precision, and accuracy, with the latter judged by comparison with Kow values for polybrominated diphenyl ethers and polychlorinated naphthalenes as reported in the literature, a gradient elution combined with an exponential calibration curve is recommended for estimating the Kow of HHCs. To our knowledge, the first isomer-specific Kow values for hexabromocyclododecane are reported. Bearing in mind that the influence of structural characteristics on retention is likely to increase with hydrophobicity, it is not justified to judge a HPLC-based Kow estimation method as being suitable for HHCs because it is shown to work well for less hydrophobic substances. Whereas univariate linear regressions often may prove to be sufficient when dealing with substances having a log Kow, of less than five, methods for HHCs need to account for the influence of structure on retention.

RP-HPLC measurement and quantitative structure - property relationship analysis of the n-octanol - water partitioning coefficients of selected metabolites of polybrominated diphenyl ethers

“…[18][19][20] This contradicted findings were due to the methods utilised, including initial composition of the mobile phase, the increased rate and mode (linear or non-linear) of methanol content, and the flow rate. The set of reference compounds and their uncertain log K OW values may have had an influence as well.…”

“…This is partly consistent with the phenomena observed in the literature. [31,32] The high organic modifier fraction required for the highly hydrophobic compounds in the isocratic elution may make the similarity between the stationary phase-eluent system and the octanol-water system become increasingly tenuous, and gradient elution is considered to be more suitable for the highly hydrophobic compounds, [18,20] but linear correlation between log k w and log K OW has been observed in the literature for log K OW as high as 8. [32] Judging from the significant similarity of these two calibration curves between log k w and log K OW for log K OW ≤ 7.2 of calibration chemicals in the present study, the log K OW values of the PBDE metabolites estimated by extrapolated retention indices appears to be more reliable, based on the stronger statistical correlation of that regression.…”

“…It can be operated on both isocratic and gradient elution, whereas the latter was considered to be more suitable for highly lipophilic chemicals. [18][19][20] Quantitative structure-property relationships (QSPR) study is another widely accepted way to estimate log K OW and other properties. It is based on the premise that molecular properties may be related to the chemical structures, which can be characterised by some structural descriptors.…”

Development of negligible depletion hollow fiber membrane-protected liquid-phase microextraction for simultaneous determination of partitioning coefficients and acid dissociation constants

“…The distribution coefficient between 1-octanol and water (D OW ) and acid dissociation constant (pK a ) of an ionizable compound are key parameters that are related to pharmacokinetic and environmental behaviors, i.e., sorption, distribution, metabolism, elimination, and toxicity [1,2]. Since the D OW of an ionizable compound is pH dependent, the pH independent partitioning coefficient of its neutral molecular form (K OW ) is generally reported in the literature.…”

Overview of the Current State-of-the-Art for Bioaccumulation Models in Marine Mammals

“…These percentages are therefore best taken from species other than marine mammals as a proxy (e.g., [26] for humans). For environmental contaminants, log K ow values are often available in the literature [33][34][35][36][37]. In a specific tissue of interest, the kinetics of a chemical can be described by two types of processes: "diffusion-limited" and "flow-limited".…”