Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Kang, Ju‐Seop; Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Hyun; Jun, Min-Young

doi:10.4196/kjpp.2011.15.2.67

Cited by 34 publications

(21 citation statements)

References 243 publications

(257 reference statements)

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“…1), vigabatrin selectively inhibits GABA-transaminase in the brain. Indeed vigabatrin is classed as a suicide inhibitor since it is transformed by GABA-transaminase to an active metabolite which irreversibly binds to the enzyme, preventing GABA physiological degradation (Kang et al, 2011).…”

Section: Chromatographic Resolution Of Chiral Aedsmentioning

confidence: 99%

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

Fortuna

Alves

2013

Biomedical Chromatography

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A large number of the antiepileptic drugs (AEDs) presently available for clinical practice are chiral compounds while others, although achiral, may originate pharmacologically active chiral metabolites in vivo. The well-known implications of chirality in pharmacokinetics and pharmacodynamics demand the investigation of pharmacological properties for a racemic mixture and each enantiomer. To achieve these objectives, appropriate chiral analytical methods must be available. This article provides the first review of the current state of the art in chiral chromatographic methods available for quantifying enantiomers of AEDs in distinct matrices. Particular attention is paid to the methodological aspects and optimization strategies that successfully allow enantiomeric chromatographic separation of chiral AEDs and/or metabolites. Furthermore, the relevance of these methods in supporting the discovery and development of chiral AEDs is emphasized. In parallel and whenever available, the principal validation parameters are herein considered and related to the stage of drug discovery and development. In an attempt to optimize anticonvulsant activity and simultaneously diminish toxic effects, many pharmaceutical companies have started to manufacture single enantiomers. Therefore, chiral chromatographic techniques will be essential and the information herein compiled can be used as a framework for developing them.

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Section: Chromatographic Resolution Of Chiral Aedsmentioning

confidence: 99%

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

Fortuna

Alves

2013

Biomedical Chromatography

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“…Comparison of the values by paired t -test indicated that the FPIA concentrations were significantly greater (p<0.001) than those obtained by HPLC method. The probable reason for this was interference by CBZ metabolites, mainly by CBZ-EP, with FPIA technique (Kang et al, 2011;Wilson et al, 1992).…”

Section: Application To Patient Plasmamentioning

confidence: 99%

“…Most commonly applied methods for the routine monitoring of CBZ alone in plasma were commercial reagentbased techniques like as fluorescence polarization immunoassay (FPIA) and enzyme multiplied immunoassay technique (EMIT), especially in clinical settings (Kang et al, 2011). However, the antibodies used in these procedures, may sometimes cross-react with CBZ metabolites, leading to an overestimation of CBZ plasma levels, and to the lower specificity of the immunoassays (Kang et al, 2011;Eadie, 1998;Wilson et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

Ribarska¹,

Sterjev²,

Cvetkovska³

et al. 2011

Maced. Pharm. Bull.

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Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v) as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

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“…According to Kang et al . (), most of these methods reported a lack of selectivity, sensitivity and reliability for LEV in routine monitoring laboratories.…”

Section: Introductionmentioning

confidence: 99%

A simple and cost‐effective HPLC‐UV method for the detection of levetiracetam in plasma/serum of patients with epilepsy

Engelbrecht

Grobler

Rheeders

2017

Biomedical Chromatography

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A simple, fast and cost-effective method was developed and validated for the determination of levetiracetam (LEV) in plasma/serum of patients using high performance liquid chromatography (HPLC) with ultraviolet detection. The stability of LEV plasma/serum samples over time and in different blood collection tubes was evaluated. Serum/plasma samples were deproteinized by methanol spiked with the internal standard, gabapentin. HPLC was carried out on a Venusil XBP C , 250 × 4.6 mm, 5 μm column, at a flow rate of 1.0 mL/min and with mobile phase consisting of 50 mm potassium dihydrogen phosphate-acetonitrile at a pH of 5.5. The UV detector was set at 205 nm and 10 μL was injected. Total runtime was 15 min. Calibration curves were linear (correlation coefficient = 0.999) over a concentration range of 1-60 μg/mL. Relative standard deviation values for both the inter-day and intra-day precision and accuracy were <5% for the concentration range. The influence of different collection tubes and the effect of time on the stability of LEV was investigated. These factors may cause inaccuracies owing to drug-protein binding and interference in the matrix. This method is simple, fast, cost-effective, reliable and accurate with minimal sample preparation for daily routine use in therapeutic drug monitoring.

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Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Cited by 34 publications

References 243 publications

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

A simple and cost‐effective HPLC‐UV method for the detection of levetiracetam in plasma/serum of patients with epilepsy

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