Carbarnazepine 5 and carbamazepine-10, 11-epoxide- 6, containing 90% 13C at position 10 were synthesized and utilized as internal standards for the quantitative analysis of the parent drug and its metabolite from the plasma of treated rhesus monkeys. A typical analysis involved the addition of a 50 μl methanolic stock solution containing 500 ng of 3 and 100 ng of 4 to 0.5 ml of plasma. The plasma was extracted and analyzed by GC/CI/MS. The precision of the assay, based on 16–18 standard curves obtained over a period of two months was: 4% and 11% for carbamazepine at concentrations of 2 μg/ml and 0.2 μg/ml, respectively and 7% and 11% for carbamazepine-10,11-epoxide at concentrations of 0.2 μg/ml and 0.02 μg/ml, respectively.
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Trager et al. (1978) studied this question.
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