Determination in plasma of a new antiepileptic drug, dl-(5 alpha,9 alpha,11S*)-5,6,9,10-tetrahydro-N,N-dimethyl-5,9-methanobenzocycloo cten-11-amine hydrochloride, and its N-desmethyl metabolite by liquid-solid extraction and capillary gas chromatography.
We have developed a sensitive and accurate method for the determination in plasma of the antiepileptic drug dl-(5 alpha,9 alpha,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 C2 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.
Yonekawa
W D
WD
Kapetanovic
I M
IM
Kupferberg
H J
HJ
Paanakker
J E
JE
van de Laar
G L
GL
D000927:Anticonvulsants / Q000097:blood*; D001643:Bridged Bicyclo Compounds / Q000097:blood*; D001952:Bridged-Ring Compounds / Q000097:blood*; D002849:Chromatography, Gas; D006801:Humans; D013997:Time Factors
D000927:Anticonvulsants; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; C049281:5,6,9,10-tetrahydro-N,N-dimethyl-5,9-methanobenzocycloocten-11-amine; C049284:5,6,9,10-tetrahydro-N-methyl-5,9-methanobenzocycloocten-11-amine