Zero-crossing derivative spectrophotometry and liquid chromatographic method for the quantitative determination of clopidogrel in presence of HMG Co-A reductase inhibitors

Abstract

In this work, two methods are described for the simultaneous determination of clopidogrel bisulfate with HMG Co-A reductase inhibitors/statins. The first method comprised of quantitative determinations of clopidogrel bisulfate in presence of HMG Co-A reductase inhibitors (atorvastatin, pravastatin simvastatin and rosuvastatin) in buffers of pH 1, 4 (simulating gastric environments), pH 7.4 (simulating blood pH) and pH 9 (simulating intestinal pH) at body temperature (37oC) using UV/VIS spectrophotometer. Derivative spectroscopy coupled with zero-crossing measurements was used for separating the interfering wavelengths of clopidogrel and statins. Least square regression analysis was performed to measure the concentrations of these drugs. It was observed that clopidogrel interacted with statins at all four pH, especially in simulated gastric environments. In the second case, reversed phase liquid chromatographic (RP-LC) method was developed for simultaneous determination and to investigate the interactions between clopidogrel and HMG Co-A reductase inhibitors. These interactions were evaluated by RP-LC in buffers of pH 1, 4, 7.4 and 9. These studies further supported the evidence of complexation between clopidogrel and statins as the area under the curve (AUC) was found increased in almost all four pH solutions.