Desenvolvimento de procedimentos analíticos para a determinação de N-acetilcisteína em produtos farmacêuticos.
Resumen
In this dissertation four analytical procedures for the determination of Nacetylcysteine
in pharmaceutical formulations are described. The first procedure
developed was a flow injection analysis system for turbidimetric determination of Nacetylcysteine
employing Ag+ ions in an acid medium as the precipitant reagent. In
this system, 250 µL of 0.01 mol L-1 AgNO3 solution and 500 µL of sample solution
were inserted simultaneously into a merging zones flow system. After the precipitate
formation in a 100 cm coil reactor, the precipitate generated was monitored
turbidimetrically at 400 nm. Desionised water flowing intermittently at 6.3 mL min-1
was used to wash out the precipitate during the sampling stage. The analytical curve
was linear in the N-acetylcysteine concentration range from 1.0 x 10-4 to 1.0 x 10-3
mol L-1; with a detection limit of 8.0 x 10-5 mol L-1 (3σB/slope) and sampling frequency
of 60 h-1 was obtained. The relative standard deviation was smaller than 1% for Nacetylcysteine
solutions in the concentrations of 1.0 x 10-4 and 5.0 x 10-4 mol L-1
(n=20). The recoveries obtained for two samples ranged from 104 to 122%. A flow
injection system with spectrophotometric detection is proposed for determining Nacetylcysteine
in pharmaceutical formulations. In this system, N-acetylcysteine was
oxidized by Fe(III) and the Fe(II) produced is spectrophotometrically monitored as
Fe(II)-1,10-phenantroline complex at 515 nm. Under the optimum analytical
conditions, the linearity of the calibration graph for N-acetylcysteine ranged from 1.8 x
10-5 to 1.5 x 10-4 mol L-1. The detection limit of 6.3 x 10-6 mol L-1 (3σB/slope) and
recoveries between 102 to 113 % were obtained. The preparation and
electrochemical characterization of a carbon paste electrode modified with copper (II)
hexacyanoferrate(III) (CuCHF) as well as its behaviour as electrocatalyst toward the
oxidation of N-acetylcysteine were investigated. The electrochemical behaviour of the
modified electrode and the electrooxidation of N-acetylcysteine were explored using
sweep linear voltammetry. The best voltammetric response was observed for a paste
composition of 20%(w/w) copper (II) hexacyanoferrate(III) complex, acetate buffer
solution at pH of 6.0 as the electrolyte and scan rate of 10 mV s-1. A linear
voltammetric response for N-acetylcysteine was obtained in the concentration range
xiv
from 1.2 x 10-4 to 8.3 x 10-4 mol L-1, with a detection limit of 6.3 x 10-5 mol L-1
(3σB/slope). The proposed electrode is useful for the quality control and routine
analysis of N-acetylcysteine in pharmaceutical formulations. Finally, a simple,
precise, rapid and low-cast potentiometric method for N-acetylcysteine determination
in pure form and in pharmaceutical preparations is proposed. N-acetylcysteine
present in tablets containing known quantity of drug was potentiometrically titrated in
aqueous solution with AgNO3. No interferences were observed in the presence of
common components of the tablets as saccharin, sucrose and EDTA. The analytical
results obtained by applying the proposed method compared very favorably with
those obtained by the comparative method. Recovery of N-acetylcysteine from
various tablets dosage formulations range from 98.7 to 103.0%. Compared to others
procedures reported in the literature the procedures developed in this dissertation
shows to be better and cheaper to determination of N-acetylcysteine in
pharmaceutical formulations.