Abstract
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.
Highlights
Carbamazepine (CBZ) (5-H-dibenze [b,f] azepine-5carboxamide), a tricyclic lipophilic compound is a first line antiepileptic drug used in the treatment of partial and gen-Jasmina Tonic-Ribarska, Zoran Sterjev, Emilija Cvetkovska, Igor Kuzmanovski, Gordana Kiteva, Ljubica Suturkova, Suzana Trajkovic - Jolevska et al, 2009)
The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC with UV detection for the simultaneous determination of plasma levels of carbamazepine and its main metabolite, carbamazepine 10, 11-epoxide, in order to obtain results of adequate quality and reliability to assure the implementation of the proposed bioanalytical method for the therapeutic monitoring of carbamazepine and its active metabolite
In order to establish the chromatographic conditions for the determination of CBZ and CBZ-EP in plasma, number of literature data were reviewed and many experiments were made
Summary
Carbamazepine (CBZ) (5-H-dibenze [b,f] azepine-5carboxamide), a tricyclic lipophilic compound is a first line antiepileptic drug used in the treatment of partial and gen-Jasmina Tonic-Ribarska, Zoran Sterjev, Emilija Cvetkovska, Igor Kuzmanovski, Gordana Kiteva, Ljubica Suturkova, Suzana Trajkovic - Jolevska et al, 2009). CBZ is usually administered at oral daily doses ranging from 400 to 1600 mg, which result in CBZ plasma concentrations in therapeutic range of 4-12 μg/ml. With monotherapy of CBZ, the steady-state of CBZ-EP plasma concentration is equivalent to 20%-25% of the parent drug (Sillanpaa et al, 2009; Shen et al, 2001; Liu and Delgado, 1999). Carbamazepine has a narrow therapeutic index, and the relationship between dose and plasma concentrations of carbamazepine may be unpredictable because of differences in genetics, age, gender, absorption, autoinduction and disease state between individuals. The presence of numerous clinically significant drug interactions supports the need of using therapeutic monitoring of carbamazepine as an essential tool in designing a safe and effective therapeutic regimen for patients with epilepsy (Sillanpaa et al, 2009; Patsalos et al, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
