Desenvolvimento e validação de metodologia para análise de valdecoxibe. Avaliação de efeitos sobre parâmetros hematológicos

Abstract

Valdecoxib is a non-steroidal anti-inflammatory drug that represents a second-generation of cyclooxygenase-2 enzyme inhibitor and possesses anti-inflammatory, analgesic and antipyretic activities. In this work a reversed-phase liquid chromatography procedure was developed and validated for the quantitative determination of valdecoxib in solid dosage forms and dissolution studies, and the evaluation of the sub-acute effects on the hematological parameters of animal model as well. Valdecoxib samples were also submitted to the physicochemical tests, meeting the specifications. The identification and quantitation analyses were performed by liquid chromatography on a Synergi fusion C18 column (150 mm x 4.6 mm i.d.; 4 µm particle size), held at 30º C. The mobile phase consisted of water, pH 7.0/acetonmitrile (52:48, v/v), with run at a flow rate of 1.0 mL/ min, with UV detection at 210 nm. The method was validated evaluating parameters such as the specificity, sensitivity, linearity (r2=0.9999), range, precision, accuracy, and robustness. The dissolution test was developed with 0.5% of sodium lauryl sulfate in water as dissolution medium using an apparatus paddle at a stirring rate of 75 rpm and quantitation by liquid chromatography. The effects of valdecoxib on the hematological parameters were evaluated by the prothrombin time (PT), activated partial thromboplastin time (APTT), levels of fibrinogen, platelet count, anti-factor Xa and anti-factor IIa activity. The results of the APTT, PT and anti-factor Xa activity showed, preliminary, that valdecoxib could increase the risk of thromboembolic complications, thus the procedures and evaluations carried out can be helpful to understand the side effects and safe use of the drug improving the quality control of the pharmaceutical product.