Utilização da eletroforese capilar como técnica analítica para a determinação de aminoglicosídeos em sistemas de liberação controlada e formulações farmacêuticas

Abstract

Leishmaniasis are diseases that have been causing challenges for public health in developing countries and, for this reason, several studies have been trying to develop a more effective formulation to fight them. According to the literature, the use of a formulation containing paromomycin (PM) produces more efficient effects when associated with gentamicin (GM) for the treatment of certain species of leishmaniasis. To evaluate matrices containing PM and GM, it is necessary to use an analysis method capable of separating and quantifying these analytes, which is a challenge due to the complex nature of the mixture of these antibiotics as well as the absence of chromophoric groups in their structures. Thus, the objective of this work was to evaluate the use of different derivatizing agents (dansil chloride (DNS), 9-fluorenylmethyl chloroformate (FMOC-Cl), methoxybenzenesulfonyl 4-chloride (MBSC), 1,2-naphthoquinone-4-sulfonic acid (NQS), phenyl isothiocyanate (PITC) and orthophthaldehyde (OPA) for separation of GM and PM by capillary electrophoresis coupled with diode array detector, beyond the development of a method for indirect detection using imidazole in the running electrolyte. NQS, FMOC-Cl and DNS were unsatisfactory for separating the drugs under the conditions tested. The best results obtained for separation and quantification of GM and PM were achieved using OPA and under the following conditions: running electrolyte containing 40 mmol L-1 of TBS, 3 mmol L-1 of beta cyclodextrin (β-CD) and 15.5% of methanol (MeOH), pH 9.0, temperature of 23 ° C, applied voltage of 16 kV, injection of 50 mbar x 5 s, capillary of 75 µm d.i x 40 cm of total length (31.5 cm in effective length) and detection at 230 nm. The validation tests were satisfactory and the values obtained of precision and recovery were in the range of 0.1 - 15.5% and 76.2 - 108.7%, respectively. A simple and fast method was also developed using indirect detection, in which the optimized conditions were: running electrolyte containing 30 mmol L-1 of imidazole, pH = 2.5. The total capillary length was 58.5 cm (50 cm effective length), with an injection of 30 mbar x 7 s. The applied voltage was 11 kV in a temperature of 29 ˚C and detection at: reference 400nm / signal: 214 nm. In addition, these methods were applied to pharmaceutical samples and samples of controlled release systems containing PM and GM. These applications were compared with a spectrophotometric method already described in the literature for analysis of aminoglycosides.