Rapid micromethod for simultaneous measurement of oxcarbazepine and its active metabolite in plasma by high–performance liquid chromatography

Abstract

A rapid method for the simultaneous determination of oxcarbazepine (OXC) and its active metabolite (10-hydroxycarbazepine) in human and rat plasma by reversed phase high-performance liquid chromatography is described. The method involves a simple one-step extraction of the drugs from plasma with dichloromethane. The extract was evaporated and the residue was reconstituted with mobile phase and injected onto a Novapak C18 column. The eluting solvent was 20% acetonitrile in water at a flow rate of 1.5 ml/min and the detector was monitored at 215 nm. The detection limit of OXC and 10-hydroxycarbazepine was 50 and 20 ng/ml, respectively. The within-day and between-day coefficients of variation for OXC and its active metabolite were 2.57-6.95% and 4.21-8.3%, respectively. The relative and absolute recoveries varied between 71.4% and 104.0%. The applicability of the analytical procedure to pharmacokinetic studies was illustrated.

Liquid chromatography–electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma

“…Most of the published methods involved tedious liquid-liquid [17,25,27,29,32,35,36] or solid-phase [18,19,26,28] extraction of the biological samples. In other published methods, acetonitrile was added to plasma samples to precipitate the plasma proteins [31,33,34].…”

“…To date, some HPLC methods with ultra-violet [17][18][19][24][25][26][27][28][29][30][31][32][33][34] or mass spectrometry [10,11,35,36] detection for determining CBZ and/or OXCBZ in biological fluids (plasma, urine) have been published. Some of them involved both the quantitation of CBZ or OXCBZ and their main metabolites (CBZ-EP, 10-OH-CBZ, DiOH-CBZ [19,24,[26][27][28][29][30][31]33,34]. Other methods allow to quantify either CBZ, CBZ-EP, 10-OH-CBZ, DiOH-CBZ and the 9-acridan [25,32], or the hydroxylated compounds (2-hydroxycarbamazepine (2-OH-CBZ); 3-OH-CBZ) [18].…”

Parent drug and/or metabolite? Which of them is most appropriate to establish bioequivalence of two oral oxcarbazepine formulations in healthy volunteers?

“…An adaptation of the HPLC method previously described for the simultaneous assay of oxcarbazepine and MHD was employed [20] . Each sample was analyzed according to the following procedure: plasma sample was defrosted at room temperature and centrifuged at 1400 g for 15 minutes.…”

Simultaneous quantitative analysis of oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine in human plasma by liquid chromatography–electrospray tandem mass spectrometry

“…Currently, the high-pressure liquid chromatography (HPLC) coupled to ultraviolet detection [3,5,8,10,[16][17][18][19][20][21][22] has been widely utilized for simultaneous measurement of OXC and MHD in biological fluids. However, the more commonly discussed limitation of all these methods for antiepileptic drugs determination is the fact of the existence of the great similarity (physicochemical properties and structures) existing between these compounds [5].…”