Rapid ultraperformance liquid chromatography–tandem mass spectrometry method for quantification of oxcarbazepine and its metabolite in human plasma

Bhatt, Mitesh; Shah, Sanjay; Shivprakash,

doi:10.1002/bmc.1510

Cited by 20 publications

(9 citation statements)

References 44 publications

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“…The plasma concentrations of oxcarbazepine decreased slowly in the first hours after sampling, with elimination half‐lives from 1 to 5 h in studies with healthy volunteers treated with single or multiple doses of oxcarbazepine . The oxcarbazepine elimination half‐life (t 1/2 ) of 5.4 h obtained in the present study is also in agreement with the values reported by Bhatt et al of 8.3 ± 3.6 h in healthy volunteers treated with a single dose of 600 mg oxcarbazepine.…”

Section: Discussionsupporting

confidence: 91%

Analysis of Oxcarbazepine and the 10‐Hydroxycarbazepine Enantiomers in Plasma by LC‐MS/MS: Application in a Pharmacokinetic Study

et al. 2013

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Oxcarbazepine is a second-generation antiepileptic drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures or generalized tonic-clonic seizures in adults and children. It undergoes rapid presystemic reduction with formation of the active metabolite 10-hydroxycarbazepine (MHD), which has a chiral center at position 10, with the enantiomers (S)-(+)- and R-(-)-MHD showing similar antiepileptic effects. This study presents the development and validation of a method of sequential analysis of oxcarbazepine and MHD enantiomers in plasma using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Aliquots of 100 μL of plasma were extracted with a mixture of methyl tert-butyl ether: dichloromethane (2:1). The separation of oxcarbazepine and the MHD enantiomers was obtained on a chiral phase Chiralcel OD-H column, using a mixture of hexane:ethanol:isopropanol (80:15:5, v/v/v) as mobile phase at a flow rate of 1.3 mL/min with a split ratio of 1:5, and quantification was performed by LC-MS/MS. The limit of quantification was 12.5 ng oxcarbazepine and 31.25 ng of each MHD enantiomer/mL of plasma. The method was applied in the study of kinetic disposition of oxcarbazepine and the MHD enantiomers in the steady state after oral administration of 300 mg/12 h oxcarbazepine in a healthy volunteer. The maximum plasma concentration of oxcarbazepine was 1.2 µg/mL at 0.75 h. The kinetic disposition of MHD is enantioselective, with a higher proportion of the S-(+)-MHD enantiomer compared to R-(-)-MHD and an AUC(0-12) S-(+)/R-(-) ratio of 5.44.

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Section: Discussionsupporting

confidence: 91%

Analysis of Oxcarbazepine and the 10‐Hydroxycarbazepine Enantiomers in Plasma by LC‐MS/MS: Application in a Pharmacokinetic Study

et al. 2013

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“…TDM depends upon reliable analytical methods for the determination of plasma/serum levels of drugs and their metabolites. Several HPLC methods coupled to ultraviolet (HPLC‐UV) (Fortuna, Sousa, Alves, Falcao, & Soares‐da‐Silva, ; Greiner & Haen, ; Hunek, Burgyan, & Wang, ; Kimiskidis et al, ; Serralheiro, Alves, Fortuna, Rocha, & Falcao, ) or mass spectrometry (HPLC–MS/MS) (Bhatt, Shah, & Shivprakash, ; de Sousa Maia et al, ; Maurer, Kratzsch, Weber, Peters, & Kraeme, ; Paglia, D'Apolito, Garofalo, Scarano, & Corso, ; Subramanian, Birnbaum, & Remmel, ; Yin et al, ) detection have been developed for the determination of licarbazepine in human serum either alone or simultaneously with other antiepileptic drugs. In general, MS‐based methods are characterized by significant advantages such high sensitivity, fast analysis times and limited sample volumes; however, they often involve expensive and sophisticated equipment requiring specially trained personnel.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, in addition to its antiepileptic action, oxcarbazepine has been also used in the treatment of bipolar disorders as monotherapy or as adjunctive treatment of affective disorders (Misdrahi et al, ). A number of studies have considered, to date, the interference of antiepileptic (Bhatt et al, ; Contin et al, ; Fortuna et al, ; Greiner‐Sosanko, Giannoutsos, Lower, Virji, & Krasowski, ; Heideloff, Bunch, & Wang, ; Maurer et al, ; Subramanian et al, ; Yin et al, ) or other commonly used drugs (Fortuna et al, ; Greiner‐Sosanko et al, ) with licarbazepine quantification. Nevertheless, only one study has, thus far, investigated the interference of licarbazepine with antidepressant or antiphsychotic drugs which may be co‐prescribed with oxcarbazepine (Greiner & Haen, ).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a reversed‐phase HPLC method for licarbazepine monitoring in serum of patients under oxcarbazepine treatment

Begas

Tsakalof

Dardiotis

et al. 2017

Biomedical Chromatography

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Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders. Several HPLC methods have been developed thus far but there is lack of control for interferences from antipsychotic drugs. The aim of the present study was to develop a simple, low-cost and reliable HPLC-UV method for the determination of licarbazepine in human serum in the presence of co-administered antiepileptic, antipsychotic and commonly prescribed drugs. Sample preparation consisted of a single protein precipitation step with methanol. Separation lasted ~9 min on a reversed-phase C column using a mobile phase composed of 50 mm sodium-dihydrogen-phosphate-monohydrate/acetonitrile (70:30, v/v) delivered isocratically at 0.9 mL/min and 30°C. Wavelength was 210 nm and calibration curve was linear with r 0.998 over the range 0.2-50.0 μg/mL. Coefficient of variation was <5.03% and bias <-4.92%. Recovery ranged from 99.49 to 104.52% and the limit of detection was 0.0182 μg/mL. No interferences from the matrix or from antiepileptic, antipsychotic and commonly prescribed drugs were observed. The method was applied to serum samples of patients under oxcarbazepine treatment and proved to be a useful tool for the therapeutic drug monitoring of licarbazepine during monotherapy or adjunctive treatment of seizures or affective disorders.

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“…The use of mass spectrometry (MS) improves the selectivity during detection and enables detection of ions formed from small molecules. However, most of the reported methods have been restricted to a single drug and its metabolites, or they required time‐consuming solid‐phase extraction in the pretreatment (Breton et al ., ; Mendu and Soldin, ; Bhatt et al ., ). No simple and rapid method for routine TDM has been reported to date.…”

Section: Introductionmentioning

confidence: 97%

Detection of 22 antiepileptic drugs by ultra‐performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring

Shibata

Hashi

Nakanishi

et al. 2012

Biomedical Chromatography

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The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50 μL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C₁₈ column with a gradient mobile phase of 10 mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10 min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r² < 0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics.

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Rapid ultraperformance liquid chromatography–tandem mass spectrometry method for quantification of oxcarbazepine and its metabolite in human plasma

Cited by 20 publications

References 44 publications

Analysis of Oxcarbazepine and the 10‐Hydroxycarbazepine Enantiomers in Plasma by LC‐MS/MS: Application in a Pharmacokinetic Study

Analysis of Oxcarbazepine and the 10‐Hydroxycarbazepine Enantiomers in Plasma by LC‐MS/MS: Application in a Pharmacokinetic Study

Development and validation of a reversed‐phase HPLC method for licarbazepine monitoring in serum of patients under oxcarbazepine treatment

Detection of 22 antiepileptic drugs by ultra‐performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring

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