Carbamazepine

Abstract

In this article, the authors discuss 9-hydroxymethyl-10-carbamoyl acridan (9-OH-CBZ), another metabolite of carbamazepine (CBZ) found in serum. The retention time of unconjugated 9-OH-CBZ should be known when using a chromatographic method, because it appears in concentrations varying from one eighth to one third of the CBZ-10,11-epoxide (CBZ-E) concentration and may therefore cause analytical interactions. Liquid chromatography/electrospray mass spectrometry ((LC/ES-MS) in a serum extract identified and confirmed 9-OH-CBZ. The amount of 9-OH-CBZ present as conjugate in serum was between 42% and 65%. The correlation factor values (r) between serum concentrations of 9-OH-CBZ and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (trans-CBZ-diol), CBZ-E, and CBZ in 100 serum samples were 0.77, 0.80, and 0.53, respectively. The origin of 9-OH-CBZ is discussed.

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

“…The 9-acridan was identified using the predominant ions at m/z 255 and m/z 180; the two common ions described in the literature [10,11].…”

“…At least 30 different metabolites have been identified [6]. Three principal metabolic pathways have been described [7][8][9][10][11][12][13] (Fig. 1).…”

“…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].…”

“…One method allows to quantify CBZ, OXCBZ, CBZ-EP, 10-OH-CBZ, DiOH-CBZ and the 9-acridan [17]. Four liquid chromatography-mass spectrometry (LC-MS) methods have been published; two of them were focused mainly to the determination of the 9-acridan [10,11]. Two methods have recently been described, the first one for the determination of CBZ and CBZ-EP by tandem liquid chromatography-mass spectrometry with electrospray ionisation [35] and the second one for the determination of CBZ and 10-OH-CBZ by atmospheric pressure chemicalionization liquid chromatography/mass spectrometry [36].…”