Pharmacokinetic study of diclophenac sodium in rat plasma by high-performance liquid chromatography

Abstract

The aim of this study is to determine pharmacokinetics of diclofenac sodium in the experiment on rats by the method of high-performance liquid chromatography. Identification and quantitative determination of diclofenac sodium in the substance of diclofenac sodium were carried out by the method of high-performance liquid chromatography. For study conduct, a total of 94 male rats with body weight of 250-300 g were used. Experimental animals were subdivided into 15 groups. Diclofenac sodium was diluted in purified water and administered per os at the doses of ED 50 and ½ ED 50 , equivalent to 8 mg/kg and 4 mg/kg of animal body weight, respectively. Animals were sacrificed in 15 min, 30 min, 60 min, 90 min, 120 min, 240 min, and 360 after drug administration. For extraction of diclofenac sodium from rat plasma samples, we used a method of solid-phase extraction, which had been modified due to microconcentrations of the active substance. Dependence of diclofenac sodium concentration on time and dose was studied by the method of high-performance liquid chromatography. In the result of the study, quantitative content of diclofenac sodium substance and suitability of the doses studied (4 mg/kg and 8 mg/kg) were confirmed. The study conducted revealed no dynamics of time, during which diclofenac sodium was present in systemic blood flow, on the dose. The results, which had been proved by chromatograms of diclofenac sodium and control sample (plasma without diclofenac) for each time interval, were obtained. First concentrations of diclofenac sodium in rat plasma are registered in rat plasma in 15 min after dose administration at the doses of 4 and 8 mg/kg. That is why this time index is recommended for further preclinical and clinical studies.