HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF CARBAMAZEPINE AND METABOLITES IN HUMAN HAIR

To study the use of hair analysis in monitoring drug compliance and hi storical changes in pharmacokinetics we developed a method for the qua ntitative determination of the anti-epileptic drug carbamazepine (CBZ) and trans-10,11-dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in h air from carbamazepine users. Digestion by 1 M NaOH was found to be th e best method for isolating CBZ and CBZ-diol from hair, followed by so lid-phase extraction and reversed-phase HPLC with UV detection. Recove ries from spiked hair samples were 76-86%. Within-day precision (C.V.; n = 10) for CBZ and CBZ-diol in hair of a CBZ user containing 10.9 mu g/g CBZ and 3.2 mu g/g CBZ-diol were 1.7 and 5.0%, respectively. Sect ional hair analysis of a patient on a constant dosage of CBZ demonstra tes an exponential decrease in hair concentrations of CBZ and CBZ-diol with increasing distance from the root, probably caused by shampooing . No CBZ-IO,ll-epoxide (CBZ-epox) could be detected. However, one comp onent in the chromatogram is probably CBZ-beta-hydroxythioether, an ad duct of CBZ-epox with cysteine, or acridinethioacetal, its rearrangeme nt product. The concentration of this component does not decrease with increasing distance from the root.