Micro-determination of tolmetin in plasma by electron-capture gas chromatography

A highly sensitive, specific and precise gas chromatographic method for the determination of the anti-inflammatory agent tolmetin in micro-samples of blood plasma is described. The pentafluorobenzyl ester derivative of tolmetin, which can be detected down to picogram levels using electron-capture detection, has been prepared. The lowest concentration of tolmetin which can be measured accurately and precisely (coefficient of variation less than 15%) in a 25-microliter plasma sample is 0.1 microgram/ml. Previously reported assays require a sample size 20--80 times larger and have a detection limit of 0.5 microgram/ml. The pentafluorobenzyl ester derivatives of both tolmetin and the internal standard have been identified from their chemical ionization mass spectra. The present method was found to be in good agreement with another published gas chromatographic assay when both methods were employed to analyze the same set of plasma samples from four juvenile reheumatoid arthritic patients.