Abstract
Objective: To develop and validate high-performance liquid chromatography with photodiode array (HPLC-PDA) detector as a method for measuring carbamazepine plasma concentrations in epilepsy patients treated with monotherapy or polytherapy.Methods: Carbamazepine was extracted from epilepsy patients’ plasma through liquid-liquid extraction, using protein precipitation with chloroform. Analysis was performed using HPLC with Inertsil DS-4 C18 (4.6x150 mm), 5 μm particle size column. The optimal condition for separation was established in a mobile phase consisting of acetonitrile: water (50:50) at a flow rate of 1.0 ml/min, detected by PDA detector at 220 nm. Propylparaben was used as the internal standard. The retention time was 3.5 min.Results: Linearity was obtained over a concentration range of 0.5-16 μg/ml with r = 0.999. The method showed good intra-and inter-day precision and accuracy of more than 90% difference (% diff) and 95% relative standard deviation (RSD). Lower limit of quantification (LOQ) was 0.5 μg/ml and lower limit of detection (LOD) was 0.2 μg/ml with 100% accuracy and more than 90% precision. Recovery test was nearly 100%. Stability of carbamazepine plasma concentration in 3 epilepsy patients was measured on the first and third month of treatment, ranging between 83.5 to 98.7%. When used to compare carbamazepine as a monotherapy versus polytherapy, the method showed good selectivity.Conclusion: The present HPLC method was valid for measuring carbamazepine plasma concentrations in epilepsy patients treated with monotherapy or polytherapy. This method meets the standard in the EMEA guideline in terms of linearity, precision, and accuracy, also selectivity in epilepsy patients treated with polytherapy.
Highlights
Carbamazepine is a hydrophobic, weakly acidic, non-polar aromatic ester, highly soluble in alcohol
30% of patients with focal epilepsy do not respond to maximum dosages of carbamazepine, resulting in the need to administer polytherapy with additional anti epileptic drug (AED) to control seizures, which may lead to drug interactions
We developed a method to measure carbamazepine plasma concentration in epilepsy patients treated with carbamazepine as a monotherapy or polytherapy
Summary
Carbamazepine is a hydrophobic, weakly acidic, non-polar aromatic ester, highly soluble in alcohol (fig. 1). 30% of patients with focal epilepsy do not respond to maximum dosages of carbamazepine, resulting in the need to administer polytherapy with additional AEDs to control seizures, which may lead to drug interactions. Measurements of specific drug concentrations in the plasma of patients on polytherapy may not be reliable due to the selectivity of multidrug measurements. Previous studies indicated that HPLC was adequate, effective, suitable, simple, rapid, highly sensitive, had a good intra-day and inter-day precision and an accuracy of >90% [1,2,3,4,5,6]. The rationale of this study was to develop and validate a simple, accurate, rapid, precise, reproducible HPLC method with photodiode array (PDA) detection for quantification of carbamazepine plasma concentration. We developed a method to measure carbamazepine plasma concentration in epilepsy patients treated with carbamazepine as a monotherapy or polytherapy
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