RAPID AND ACCURATE DETERMINATION OF CLOPIDOGREL IN TABLETS BY USING SPECTROPHOTOMETRIC AND CHROMATOGRAPHIC TECHNIQUES

Quantitative determination of clopidogrel (CLP) was carried out by using zero-order and derivative ultraviolet (UV) spectroscopy. Calibration curves for CLP in 0.1N HCl between 0.10.8 mM (42-336 μg/mL) concentration range were obtained by the measurements at 267.5, 271.5 and 279.3 nm for first derivative, at 269.5, 273.4, 277.3 nm for second derivative and at 268.1, 271.3, 275.6 nm for third derivative UV spectrophotometry, respectively. In application, 270 nm in zero-order UV spectrophotometry, 279.3 nm in first derivative UV spectrophotometry, 269.5 nm in second derivative UV spectrophotometry and 275.6 nm in third derivative UV spectrophotometry were selected by their lowest relative standard deviation values in the validation studies. Mean recoveries and the relative standard deviations of the methods were found as 98.7 % and 1.90 % in zero-order UV spectrophotometry, 97.5 % and 0.76 % in first derivative UV spectrophotometry, 99.6 % and 1.25 % in second derivative UV spectrophotometry, 99.5 % and 1.15 % in third derivative UV spectrophotometry, respectively. In this study, the values of limit of detection and limit of quantitation were calculated at selected λ values as 0.01mM and 0.03 mM for zero-order (λ270 nm), 0.02 mM and 0.07 mM for first derivative (λ279.3 nm), second derivative (λ269.5 nm), third derivative (λ275.6 nm) UV spectrophotometry, respectively. The proposed methods were applied to the determination of CLP in bulk and tablets. The results were compared statistically with each other and high performance liquid chromatography (HPLC) procedure. The differences were not significant. In HPLC method, an isocratic system consisted of a Nova-Pak C18 analytical column and a mobile phase composed of pH 8 phosphate buffer : acetonitrile (30:70, v/v) at a flow rate 0.8 mL/min was used for the optimal chromatographic separation using UV detection at 210 nm. Applying HPLC method, linearity was observed in the concentration range from 1.26 to 7.55 μg/mL for CLP with a correlation coefficient 0.999. The values of the limit of detection and limit of quantitation were calculated as 0.29 μg/mL and 0.96 μg/mL, respectively. Synthetic samples were analyzed and mean recoveries and the relative standard deviations were found as 99.95 % and 0.40 % in HPLC. The spectrophotometric methods presented in this study can be used accurate, simple, economic and practical in the determination of CLP in tablets. The procedures do not require any separation step. The mean recoveries were found satisfactory in the methods. These methods also give repeatable results. Proposed methods could usefully be applied to routine quality control of tablets containing CLP. No interference was observed from common excipients in pharmaceutical formulations.