Gas chromatographic/mass spectrometric assays for oxcarbazepine and its main metabolites, 10-hydroxy-carbazepine and carbazepine-10,11-trans-diol

Abstract

Oxcarbazepine (OCB) cannot be measured undecomposed by gas chromatography, not even when injected into a cooled, inert fused-silica capillary column. The bis-trimethylsilyl derivatives of the enol of OCB and of its main metabolite, 10-hydroxy-carbazepine (10-OH-CB), and the tris-trimethylsilyl derivative of carbazepine-10,11-trans-diol (CB-trans-diol) can be obtained easily at room temperature and are well suited for gas chromatographic and gas chromatographic/mass spectrometric analysis. Thermal decomposition to the substituted iminostilbene derivatives occurs only to the extent of a few per cent under the conditions described. Two gas chromatographic/mass spectrometric assays have been developed: one for the simultaneous quantification of OCB and 10-OH-CB, the other for CB-trans-diol. Both assays use carbazepine-10,11-cis-diol as the internal standard. Using 0.5 ml of plasma, limits of detection of 0.1, 0.1 and 1 ng/ml were obtained for OCB, 10-OH-CB and CB-trans-diol, respectively. CB-trans-diol is also the main metabolite of carbamazepine in patients under maintenance therapy. The kinetics of 15N-labelled CB-trans-diol derived from a single dose of (15N)carbamazepine has been measured in plasma and urine of patients and volunteers receiving (15N)carbamazepine in several studies.

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…Multiple analytical methodologies have been reported for the measurement of 10-hydroxycarbazepine in plasma/serum including GC [129], GC/MS [130], HPLC [131,132], LC/MS [133], LC/MS/MS [134] and micellar electrokinetic chromatography [135]. TDM is justified when changes are expected that might alter 10-hydroxycarbazepine clearance including changes in renal function, pregnancy, and concomitant use of liver enzyme-inducing drugs.…”

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

“…The thermal instability of CBZ and OXCBZ makes highperformance liquid chromatography (HPLC) more attractive to use than gas chromatography [6,[21][22][23], which in addition requires a complicated derivatisation procedure as sample preparation. 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.…”

Zero Order and Area Under Curve Spectrophotometric methods for determination of Oxcarbazepine in Pharmaceutical Formulation

“…OXC is known to exert antiepileptic activity by blockade of voltage-dependent sodium channels in the brain [2]. Literature survey revealed several analytical methods voltammetry [3], chiral liquid chromatography method with ultraviolet detection (LC-UV) [4,5], micellar electrokinetic chromatography [6], microemulsion electrokinetic chromatography [7], HPLC [8][9][10][11][12][13][14][15][16][17][18][19][20], capillary electrophoresis [21], GC-MS [22] and spectrophotometry [23][24] have been reported in bulk, pharmaceutical dosage form for determination of Cefadroxil. Hence an attempt has been made to develop new Zero Order and Area under Curve Spectrophotometric methods for estimation of Oxcrabazepine in bulk and pharmaceutical formulations with good accuracy simplicity, precision and economy.…”