Naslov
Therapeutic drug monitoring: quantitation of oxcarbazepine and its active metabolite in human serum

Autori
Lovrić, Mila ; Lalić, Zdenka ; Božina, Nada ; Granić, Paula ; Sertić, Jadranka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum biologorum. Supplement 2. / Banfić H., Boban M., Francetić I., Klarica M., Mück-Šeler D., Pivac N., Sabolić I., Tvrdeić A., Župan G. - Osijek : Hrvatsko farmaceutsko društvo, 2007, 130-130

Skup
5th Croatian Congress of Pharmacology and 2nd Congress of Croatian Physiological Society with international participation

Mjesto i datum
Osijek, Hrvatska, 19.09.2007. - 22.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
oxcarbazepine; drug monitoring; HPLC; human serum

Sažetak
Introduction: Oxcarbazepine (Trileptal) is a keto-derivative of carbamazepine. It was developed by introducing minimal changes in the structure of carbamazepine, which altered the metabolism to avoid the production of epoxide metabolite. Oxcarbazepine is rapidly metabolized to a pharmacologically active monohydroxy metabolite (MDH ; 10-hydroxy-carbazepine, licarbazepine). 10-hydroxy-carbazepine has independent anticonvulsant properties and is mainly responsible for the effect of oxcarbazepine. The aim of this study was to develop and validate a HPLC method for measuring oxcarbazepine and 10-hydroxy-carbazepine simultaneously with other antiepileptics (lamotrigine, carbamazepine, phenobarbitone, phenytoin) which are already in routine use in our laboratory. Materials and Methods: Serum sample (250 _L) pretreatment was based on liquid extraction with ethylacetate/hexane, evaporated and desolved in 200 _L mobile phase. The separation was obtained on reverse-phase column (C18, 250X4, 6 mm I.D. 5_m) using a phosphate buffer/acetonitrile/methanol mixture (pH 6, 8) as a mobile phase, at the flow rate of 1.3 ml/min andDADdetector at 237nm ; total time for chromatographic separation was 13 min. Results: The calibration curves were linear for both analytes (r= 0.9975) in the expected therapeutic range. Intermediate precision (inter-day) expressed as relative standard deviations was less than 3% for 10-hydroxy-carbazepine and oxcarbazepine at two concentration levels. Accuracy, expressed as percent error, ranged from 94.5-103.8% for 10-hydroxycarbazepine and from 88-100% for oxcarbazepine. The limit of quantitation was 2.07 _mol/L for 10-hydroxy-carbazepine and 0.08 _mol/L for oxcarbazepine. Conclusion: Based of analytical parameters (linearity, precision, accuracy, limit of quantitation), the presented method is suitable for pharmacokinetic studies and therapeutic drug monitoring. The method shows good specificity with other prescribed drugs. While less pronounced than for carbamazepine, pharmacokinetic variability for oxcarbazepine was still considerable, and it can be affected by age, pregnancy, concurrent disease and drug-drug interaction. These characteristics suggest that therapeutic drug monitoring may be of value in treatments with oxcarbazepine.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Farmacija

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