Desenvolvimento de métodos para determinação de metilbrometo de homatropina em produtos farmacêuticos empregando turbidimetria em fluxo e titulação condutimétrica

Abstract

Antimuscarinic compounds are drugs, which play important role on the central nervous system. The most widely used are atropine, escopolamine, homatropine and homatropine methylbromide. These drugs are utilized in several clinical situations, and, because of this, it is necessary to develop simple, fast and effective analytical procedures for the dosage of these pharmaceuticals. In this work, three procedures for the determination of homatropine methylbromide in the pharmaceuticals were described: two with turbidimetric detection, and one with condutometric detection. In the first procedure, the homatropine methylbromide (C16H21NO3.CH3Br)reacted with silicotungstic acid (H4Si(W3O10)4) forming a precipitated ([C16H21NO3.CH3]4[Si(W3O10)4](s)), which was measured at 410 nm. A volume of 125µL of the 1.0x10-3 mol L-1 silicotungstic acid solution and a sample volume of 375µL were introduced into a carrier at flow rates of 2.0 mL min-1 and 3.9 mL min-1 respectively and a tubular coiled reactor of 50 cm was used. A solution of 0.05 mol L-1 HCl was used to carry the sample and reagent solutions. The analytical curve was linear in the homatropine methylbromide concentration range from 8.1 x 10-5 to 2.2 x 10-4 mol L-1 (r=0,996), with a detection limit of 5.0 x 10-6 mol L-1 (3σB /slope). Relative standard deviations (RSD) of smaller than 1.5% were obtained for the homatropine methylbromide solutions in the concentrations of 1.08 x 10-4 and 1.62 x 10-4 mol L-1 (n=10). Recoveries ranging from 96.0 to 103.0% were obtained. This method was applied in the determination of this drug in the pharmaceuticals, with a sample throughput of 70 h-1.In the other flow injection procedure, the homatropine methylbromide (C16H21NO3.CH3Br) reacted with AgNO3 forming a precipitated AgBr(s), which was measured at 410 nm. A volume of 25µL of the 1.0x10-2 mol L-1 AgNO3 solution and a sample volume of 375µL were introduced into a carrier at flow rates of 2.0 mL min-1 and 3.9 mL min-1 respectively and a tubular coiled reactor of 50 cm was used. The analytical curve was linear in the homatropine methylbromide concentration range from 8.0 x 10-4 a 1.7 x 10-3 mol L-1 (r= 0,998), with a detection limit of 9.5 x mol L-1 10-5 (3σB /slope). Relative standard deviations (RSD) smaller than 2.0% were obtained for 1.2 x 10-3 and 1.5 x 10-3 mol L-1 homatropine methylbromide solutions (n=10). Recoveries ranging from 94.9 a 104,0% were obtained. This method was applied in the determination of this drug in the pharmaceuticals, with a sample throughput of 75 h-1. In the final condutometric procedure, 10 mL of either the sample solution or the homatropine methylbromide solution (C16H21NO3.CH3Br) was titrated with 1.0x10-3 mol L-1 AgNO3 at 200 rpm and 25°C. The LD was 1.0x10-4 mol L-1.