A METHOD FOR MEASURING OCTANOL:WATER PARTITION COEFFICIENTS OF HIGHLY TOXIC ORGANOPHOSPHORUS COMPOUNDS

Abstract

Octanol:water partition coefficients (log P) can be used to provide invaluable information for the overall understanding of the uptake, distribution, biotransformation, and elimination of a wide variety of chemicals. This is especially important in the study of certain classes of organophosphorus compounds, e.g., chemical warfare agents. Although several analytical methods currently exist for providing the necessary data for determination of log P values, their use in the study of chemical warfare agents has been limited due to the rapid hydrolysis and biolethality of this class of compounds. To overcome those limitations a rapid, convenient, and safe method for generating the required data was developed using a computer-controlled gas chromatograph (GC) equipped with a nitrogen phosphorus detector. For method development four organophosphorus compounds were used:diisopropyl methyl phosphonate (DIMP), diethyl p -nitrophenyl phosphate (paraoxon), diisopropyl fluorophosphate (DFP), and pinacolyl methylphosphonofluoridate (soman). The method was capable of determining the concentration of DIMP in hexane over the concentration range of 1 to 1 × 10-4 mg / m L by comparing the GC peak areas to analytic standards (r2=0.999). The latter concentration was found to be the limiting concentration for qualitative analysis. A concentration of analyte of 10-2 mg / m L was found to provide excellent quantitative results. The intra- and interanalysis coefficient of variation (CV) for DIMP, over the concentration range 10-1 to 10-2 mg / m L in octanol subsequently diluted 1:100 in hexane or in water subsequently extracted with an equal volume of octanol followed by a 1:100 dilution in hexane, were 7.3 and 3.5%, respectively. The intra- and interanalysis CV for paraoxon, DFP, or soman, each at a fixed concentration of 10-2mg / m L in the same two solvents and treated in the same manner as DIMP, were 4.0 and 5.6% for paraoxon, 3.3 and 3.6% for DFP, and 0.7 and 1.1% for soman, respectively. Log P values were determined and found to be 0.478 for DIMP, 1.600 for paraoxon, 1.173 for DFP, and 1.824 for soman. All results were in excellent agreement with previously determined theoretical or experimental values. Based on the log P determined for DFP and soman it was possible to estimate the fluorophosphate and fluorophosphonate fragment values to be 2.14 and 1.97, respectively. Using this method toxic organophosphorus compounds at a concentration of 10-2 mg / m L could be analyzed directly in octanol, the organic solvent used for log P determinations. This analytical method was reproducible, safe, and sensitive where determination of the presence of organophosphorus compounds is a desired endpoint for comparative in vitro analytical studies.