Simultaneous determination of clobazam and its major metabolite in human plasma by a rapid HPLC method.
A rapid and specific HPLC method has been developed and validated for simultaneous determination of clobazam, the anticonvulsant agent, and its major metabolite in human plasma. The sample preparation was a liquid-liquid extraction with tuloene yielding almost near 100% recoveries of two compounds. Chromatographic separation was achieved with a Chromolith Performance RP-18e 100 mm x 4.6mm column, using a mixture of a phosphate buffer (pH 3.5; 10mM)-acetonitrile (70:30, v/v), in isocratic mode at 2 ml/min at a detection wave-length of 228 nm. The calibration curves were linear (r(2)>0.998) in the concentration range of 5-450 ng ml(-1). The lower limit of quantification was 5 ng ml(-1) for two compounds studied. The within- and between-day precisions in the measurement of QC samples at four tested concentrations were in the range of 0.89-9.1% and 2.1-10.1% R.S.D., respectively. The developed procedure was applied to assess the pharmacokinetics of clobazam and its major metabolite following administration of a single 10mg oral dose of clobazam to healthy volunteers.
Rouini
Mohammadreza
M
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Research Centre, Tehran University of Medical Sciences, 14155-6451 Tehran, Iran. rouini@sina.tums.ac.ir
Ardakani
Yalda H
YH
Hakemi
Lida
L
Mokhberi
Maryam
M
Badri
Gheise
G
D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001569:Benzodiazepines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000078306:Clobazam; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D015203:Reproducibility of Results
D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam; C024581:N-desmethylclobazam