Quantitative gas-chromatographic flame-ionization method for p-chlorophenoxyisobutyric acid in human serum and saliva.

Abstract

Abstract We describe a gas-chromatographic method for p-chlorophenoxyisobutyric acid (I) the active metabolite of clofibrate. The drug and internal standards are separated from either serum or saliva by a double extraction procedure and converted to the corresponding butyl esters by reaction with iodobutane in a mixture of methanol and N,N-di-methylacetamide containing tetramethylammonium hydroxide. Within-run CV of this assay at a serum I concentration of 79.2 mg/liter was 2.3% and at a salivary I concentration of 2.5 mg/liter was 2.1%. Precision during four months of the serum and salivary assays at these concentrations was 4.1% and 6.2%, respectively. The mean serum concentration of I (12 h after dose) in patients receiving the drug at an average dose of 28.0 mg/kg per day was 109.6 mg/liter. Serum and salivary concentrations of I as determined by our procedure were used to calculate the unbound fraction of drug in human serum. Such measurements can be used to monitor therapy in patients with renal disease, where drug toxicity may arise from high concentrations of unbound I.