Free and total reduced concentrations of D-penicillamine have been measured in the plasma of rheumatoid arthritis patients by HPLC and electrochemical detection. A reverse-phase ion-pair separation in conjunction with a dual porous graphite electrode satisfied the requirements of robustness, sensitivity, selectivity and suitable retention time. Plasma levels measured between 1·5 and 3 h after an oral dose, were <0·3 to 57·6 μmol/L and 0·6 to 85·0 μmol/L (n=26) for free and total reduced drug concentrations, respectively. Sources of error in the accurate measurement of peak plasma D-penicillamine levels were identified as oxidative loss and alteration in the free to protein-bound ratio in the period following sample collection.
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