DEVELOPMENT OF A HIGH PERFORMANCE CHROMATOGRAPHIC METHOD FOR THERAPEUTIC DRUG MONITORING OF CARBAMAZEPINE BASED ON AN EXPERIMENTAL DESIGN APPROACH
CRISTIAN TUCHILĂ 1#, DANIELA BACONI 1#*, VALENTINA ANUȚA 1#, CRISTINA ELENA DINU-PÎRVU 1#, ANA-MARIA VLĂSCEANU 1#, CRISTIAN BĂLĂLĂU 2#, MARIA MAGDALENA CONSTANTIN 3#, MIRIANA STAN 1#
1“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia Street, Bucharest, Romania
2“Carol Davila” University of Medicine and Pharmacy, Faculty of Medicine, Sf. Pantelimon Emergency Clinical Hospital,
340-342 Pantelimon Avenue, Bucharest, Romania
3“Carol Davila” University of Medicine and Pharmacy, Faculty of Medicine, Colentina Clinical Hospital, 19-21 Ștefan cel
Mare Boulevard, Bucharest, Romania
*corresponding author: daniela_baconi@yahoo.com
#All authors had equal contribution
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Abstract:
An isocratic simple and rapid HPLC-UV method has been developed and validated for the determination of carbamazepine
(CBZ) in human plasma, using nitrazepam (NTZ) as internal standard. Separation was carried out on a C18 column with a
mobile phase composed of water:acetonitrile (55:45 v/v), delivered at a flow rate of 1 mL/min. Liquid-liquid extraction with
ethyl acetate was used for the isolation of the analytes from plasma. Development of the method was based on a design of
experiments (DOE) approach. A 23 full factorial design with central points was used in order to select the experimental
parameters, while considering peak asymmetry, resolution between CBZ and the internal standard and retention time as
responses. Overall, optimization of the analysis parameters was performed using Derringer's desirability function and overlay
contour plots. The method was fully validated in the concentration range of 0.1 - 20 μg/mL, which included the entire therapeutic
range of CBZ (4 - 12 μg/mL). The method is simple, rapid (with a total analysis time of 5 minutes) and can be applied in
routine clinical investigations.

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