A vial-equilibration method to evaluate the drug-metabolizing enzyme activity for volatile hydrocarbons

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Abstract

A simple but sensitive vial-equilibration technique to evaluate liver microsomal enzyme activity for volatile hydrocarbons is described. The substrate, toluene or trichloroethylene (q mol), is incubated together with the mixture of enzyme and cofactor in a small airtight closed vial for a period of time (t). No direct determination of the product formed or of the substrate disappeared is necessary; only the ratio of gas chromatographic peak height (h′) obtained from the air phase in the sample vial (intact enzyme is used) to that (h) from the reference vial (inactivated enzyme is used) is needed to calculate the rate of enzymatic reaction (v), i.e., v = q(1−h′/h)/t. The time-activity and enzyme-activity studies proved the method to be useful for the evaluation of enzyme activity.

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    Values of Kliver are invariably determined by an in vitro method in which the gaseous solubility is determined in isolated samples of liver; nearly all the data refers to human liver. There are some analytical methods to determine the partition coefficients [4,5]. However, these methodologies are laborious, expensive, or time-consuming and require a sufficient quantity of the pure compounds, hence not suitable for high-throughput screening of various compounds.

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