科研之友
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摘要
Background: Carbamazepine is a first-choice antiepileptic drug for the treatment of simple and complex partial seizures. The use of an established therapeutic range for carbamazepine concentration is limited by the presence of carbamazepine-10,11-epoxide, its active metabolite that significantly contributes to the efficacy and toxicity and is not routinely measured and accounted for. This article describes the development of a HPLC method for determination of carbamazepine and carbamazepine-10,11-epoxide in serum, and compares it with chemiluminescence immunoassay to evaluate the importance of considering the active metabolite in therapeutic strategies. Methods: The procedure involves protein precipitation, separation on a reverse-phase column and ultraviolet detection. The analytical procedure proved to be sensitive, selective, precise, accurate and linear (regression coefficients > 0.999) in the range of 0.5-25.0 mg/mL and 0.1-10.0 mg/mL for quantification of carbamazepine and carbamazepine-10,11-epoxide, respectively. For the comparison between methods, serum samples of 75 patients using the medication were evaluated. Results: The Pearson correlation coefficient showed that the carbamazepine concentrations measured by HPLC are significantly higher than those obtained by immunoassay (mean difference of 1.07 mg/mL, 95% limits of agreement from -0.65 to 2.80 mg/mL). Conclusions: This difference may be decisive for the therapy. In some cases, this may affect the individual dosage adjustment and subsequent treatment. Clin Chem Lab Med 2009;47:458-63.
- 出版日期2009-4
