Determination in plasma of a new antiepileptic drug, dl-(5α,9α,11S)-5,6,9,10-tetrahydro-N,N-dimethyl-5,9-methanobenzocycloocten-11-amine hydrochloride, and its N-desmethyl metabolite by liquid—solid extraction and capillary gas chromatography

• Published in: Journal of chromatography. Biomedical applications 1986, Vol.377, p.205-212
• Main Authors: Yonekawa, W.D., Kapetanovic, I.M., Kupferberg, H.J., Paanakker, J.E., Van De Laar, G.L.M.
• Format: Article
• Language: English
• ISSN: 0378-4347
• DOI: 10.1016/S0378-4347(00)80775-6

We have developed a sensitive and accurate method for the determination in plasma of the antiepileptic drug dl-5α,9α,11S*)-5,6,9,10-tetrahydro-N,N-dimethyl-5,9-methanobenzocycloocten-11-amine hydrochloride and its N-desmethyl metabolite. The extraction procedure utilizes base-treated disposable C 2 solid-phase columns, with the analyte eluted with organic solvent. Nitrogen-selective gas chromatography is used for detection. Linear regression analysis showed that the method is linear between 4 and 1500 ng/ml for the parent drug and between 8 and 3000 ng/ml for the N-desmethyl metabolite. Intra- and inter-day variability, as shown by the coefficient of variation, is less than 8% for both compounds. The method is applicable to routine plasma determination of both these compounds in clinical pharmacokinetic studies.