PREDICTION OF URINARY SULFATE AND GLUCURONIDE CONJUGATE EXCRETION FORSUBSTITUTED PHENOLS IN THE RAT USING QUANTITATIVE STRUCTURE-METABOLISM RELATIONSHIPS

1. The quantitative urinary excretion of the sulphate and glucuronide metabolites of 15 substituted phenols dosed to rat has been determined using high resolution F-19-nmr spectroscopy. 2. The urinary metabolic fate of each of the compounds was related to a series of calculated p hysicochemical properties for each compound to produce quantitative st ructure-metabolism relationships (QSMRs). Using these calculated molec ular properties it was possible to predict the urinary recovery of xen obiotic material as a percentage of the administered dose, to classify the compounds according to their 'dominant' metabolite pattern and to predict quantitatively the proportions of glucuronide and sulphate co njugates in the urine by the use of multiple linear regression. 3. The quantitative predictions were tested by cross-validaiton and good pre diction of total xenobiotic urinary recovery as a percentage of the ad ministered dose was achieved based on an equation involving the electr ophilic superdelocalizability at C4 (para to the hydroxyl function), t he smallest principal ellipsoid axis dimension and the heal of formati on. The largest moment of inertia and the electrophilic superdelocaliz ability; at C3 were found to be the most significant factors for the p rediction of the percentage glucuronide in the urine, and the urinary excretion of sulphate conjugates as a percentage of total urinary reco very was negatively correlated with the glucuronide excretion as littl e parent compound was excreted.