DESENVOLVIMENTO E VALIDAÇÃO DE MÉTODO ANALÍTICO POR CLAE PARA DETERMINAÇÃO SIMULTÂNEA DE FÁRMACOS EM FORMULAÇÕES MAGISTRAIS E ESTUDO DE COMPATIBILIDADE ENTRE COMPONENTES DAS FÓRMULAS

Abstract

The compounded drugs allow the treatment of diseases in a personalized way, with different dosages, according to the individual needs of each patient, besides the possibility of combining more than one drug in a single finished product. Studies have shown many analytical methods developed to determine atorvastatin (ATO), losartan (LOS), and metformin (MTF) isolated or together with other active ingredients, however, no analytical method was found in the literature for simultaneous quantification of ATO, LOS, and MTF in pharmaceutical formulations. Thus, a chemical-pharmaceutical study involving these drugs was carried out. The raw materials ATO, LOS, and MTF were characterized by absorption spectroscopy by ultraviolet (UV), infrared (IV), Thermogravimetry (TG), and Differential Scanning Calorimetry (DSC). All these techniques allowed to qualify the raw materials, to become suitable to use them as secondary reference standards. An analytical method employing High-Performance Liquid Chromatography (HPLC) was developed and validated for quantitative and simultaneous determination of these drugs, in capsules, produced by compounding pharmacies, using the Dionex® Ultimate 3000 model, a liquid chromatographic, coupled with DAD (diode-array detector), and the separation of drugs was carried out on the Sigma-Aldrich® C18 column (4.6 x 150 mm, 5μm) with a flow rate of 0.3 mL min-1 and a mobile phase composed by MeOH: H2O (78:22 v / v) adjusted the pH to 3.0, with orthophosphoric acid. The detections were performed at wavelengths of 225 nm (LOS), 236 nm (MTF), and 246 nm (ATO). The method was validated according to the official guidelines of validation, and the following criteria were performed: linearity, precision, accuracy, limits of detection (LD) and quantification (LQ), precision, accuracy, robustness, and selectivity. Symmetrical peaks of MTF, LOS, and ATO were obtained at retention times of approximately 3.05; 4.88; and 6.71, minutes, respectively. The calibration curves were linear in ranging intervals from 1.0 - 9.0 μg mL-1 for ATO, from 1.5 to 6.5 μg mL-1 for LOS, and from 12.5 to 62.5 μg mL-1 for MTF. The linear correlation coefficients values (r)> 0.99 for all drugs. The study of drug-drug compatibility revealed some physico- chemical interactions between them. The results obtained from the chromatographic method developed and validated in this research can be applied to the analysis of these drugs isolated or combined in pharmaceutical formulations in routines of the laboratory of quality control of medicines.