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Article Title

Simultaneous kinetic-potentiometric determination of levodopa and carbidopa using multivariate calibration methods

Abstract

Partial least squares (PLS) and principle component regression (PCR) multivariate calibration methods were applied to the simultaneous determination of carbidopa and levodopa using kinetic data from novel potentiometry methods. These methods were based on the rate of chloride ion production in the reaction of carbidopa and levodopa with N-chlorosuccinimide (NCS) which was monitored by a chloride ion-selective electrode. The experimental data shows suitability of ion-selective electrodes (ISEs) to be used as detectors not only for the direct determination of chloride ion but also for simultaneous kinetic-potentiometric analysis using chemometric methods. These methods are based on the differences observed in the production rate of chloride ions. The results show that simultaneous determination of carbidopa and levodopa can be performed in their concentration ranges of 1.0 - 14.0 and 0.5 - 25.0 μg/mL, respectively. The total relative standard errors for applying PCR and PLS methods to 9 synthetic samples in the concentration range of 2.0 - 13.0 μg/mL for carbidopa and 1.0 - 18.0 μg/mL for levodopa were 4.81 and 4.29, respectively. The effects of certain additives used as excipients upon the reaction rate were determined to assess selectivity of the method. Both methods (PLS and PCR) were validated using a set of synthetic sample mixtures and then were successfully applied to the determination of carbidopa and levodopa in several commercially available mixture formulations. The recoveries were satisfactory and comparable to those obtained by applying the reference Pharmacopoeia method of high performance liquid chromatography.

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