High-performance liquid chromatographic determination of carbamazepine and metabolites in human hair.
To study the use of hair analysis in monitoring drug compliance and historical changes in pharmacokinetics we developed a method for the quantitative determination of the anti-epileptic drug carbamazepine (CBZ) and trans-10,11-dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in hair from carbamazepine users. Digestion by 1 M NaOH was found to be the best method for isolating CBZ and CBZ-diol from hair, followed by solid-phase extraction and reversed-phase HPLC with UV detection. Recoveries 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 microg/g CBZ and 3.2 microg/g CBZ-diol were 1.7 and 5.0%, respectively. Sectional hair analysis of a patient on a constant dosage of CBZ demonstrates an exponential decrease in hair concentrations of CBZ and CBZ-diol with increasing distance from the root, probably caused by shampooing. No CBZ-10,11-epoxide (CBZ-epox) could be detected. However, one component in the chromatogram is probably CBZ-beta-hydroxythioether, an adduct of CBZ-epox with cysteine, or acridinethioacetal, its rearrangement product. The concentration of this component does not decrease with increasing distance from the root.
Saris
L A
LA
Instituut voor Epilepsiebestrijding, Meer and Bosch, Heemstede, The Netherlands.
Brekelmans
G J
GJ
van der Linden
G J
GJ
Rademaker
R V
RV
Edelbroek
P M
PM
D000328:Adult; D000927:Anticonvulsants / Q000032:analysis* / Q000378:metabolism; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006197:Hair / Q000737:chemistry*; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000927:Anticonvulsants; D002220:Carbamazepine; C004822:10,11-dihydro-10,11-dihydroxy-5H-dibenzazepine-5-carboxamide; C012227:carbamazepine epoxide