Estratégias para a determinação de minoxidil

Abstract

In this work methods for determining minoxidil (MX) in commercial samples and electrolytes of synthetic plasma and urine are presented. The minoxidil is a pharmaceutical whose blood vessel dilation property is used in the treatment of the Arterial Hypertension and in the treatment of the Alopécia Areata. Three commercial samples were analyzed, the Regaine® (Pharmacia, USA) and the magistral formulation (Porto Bianco, Brazil) both are topical use solutions, in a mixture of ethanol and propilenoglicol as vehicle, containing 2 % (20 mg mL-1) and 5 % of minoxidil (50 mg mL-1) respectively, and Loniten® (Rhodia, Brasil) containing 10 mg of MX per tablet. Three proposals for the determination of minoxidil in commercial samples and electrolytes of synthetic plasma and urine were considered. The first procedure was the determination of MX in the samples using flow injection analysis with spectrophotometric detection in two setups. For the setup procedure using single line with a wavelength of 400 nm, which can quantify the MX present in samples, showing recovery values of 99.7 and 104.8 % for Loniten® and the Regaine® respectively, and 102.5 % for the magistral sample. In merging-zones setup, the detection was in 345 nm, the MX was determined in the samples with recovery 101.3 % for Loniten® and 99.8 % to Regaine® and 103.7 % for the magistral. For both configurations, all the results from flow agree with the labeled values and the results from the chromatographic method (comparative method) in 95 % confidence (t-Student test). In the second procedure, an electroanalytical determination of MX is described using two composite electrodes, the graphite-polyurethane (GPUE) and graphite-silicone rubber (GSRE). Cyclic voltammetry was used to study the electroactive area of electrodes (GPUE = 0.093 cm2; GSRE = 0.089 cm2), the diffusion coefficient of MX (in order of 8.0 x10-6 cm2 s-1) and to study the mechanism of electro-oxidation of MX of which involves one electron per proton. With the support of analytical curves were determined the levels of MX in the samples by different voltammetric techniques; cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV). The recovery values are in the range between 96.0 and 110 %, depending on the sample and the voltammetric technique. The electrochemical impedance spectroscopy showed that the mass transport is controlled by diffusion and also there is a weak and reversible adsorption that for both the electrodes. The third method describes the determination of MX and furosemide (FR) using high performance liquid chromatography (HPLC) with spectrophotometric detection. The wavelengths of 275 and 285 nm were for the detection of FR and MX respectively. The mobile phase used was methanol/triethylamine (99:1, V/V) in the flow rate of 0.5 mL min-1. The column used was a C18 Supelco®. The recoveries were 97.7 and 102.4 % for Loniten® and Lasix® respectively. Finally is presented the characterization of the product of oxidation of MX. The informations obtained from infrared spectroscopy technique, were compared with results obtained by nuclear proton magnetic resonance. Two structures were proposed as product of redox reaction between the MX and KMnO4, the desoximinoxidil and another new structure.