Kinetic Method for the Determination of α‐Methyldopa in Pharmaceutical Preparations: Analytical Procedure and Reaction Mechanism Considerations

Abstract

A reliable and very simple kinetic method is proposed for the determination of α‐methyldopa in pharmaceutical preparations. It is based of the oxidation of α‐methyldopa, a catechol derivative, to quinone, by the ferric ion in the presence of salicylic acid and HCl. The deep blue complex formed between iron(III) and salicylate (λ_max 525 nm) allows the reaction to be watched as absorbance decreases with the reduction of the ferric ions to ferrous with the consequent dissociation of the complex. Four pharmaceutical preparations were analyzed and the results were compared with those obtained with the spectrophotometric United States Pharmacopeia method. The statistical t‐Student and the F‐tests were applied to compare the results obtained with the two independent methods. In all cases complete agreement, in terms of accuracy and precision, was observed with a confidence level of 95% (α=0.05). Considering the four samples analyzed, using the proposed method, and five determinations for each sample, the observed mean relative standard deviation (RSD) is about 0.8%. The concentration range studied was from about 2×10⁻⁴ mol L⁻¹ to 18×10⁻⁴ mol L⁻¹ (about 40 µg/mL to 360 µg/mL) in the final solution and it is quite adequate for the analytical procedure at 25.0±0.1°C. A typical coefficient of determination, r², of the calibration curve, is 0.9994. For the kinetic pseudo first order curves a typical observed r² is 0.99998. The Arrhenius activation energy was found to be 84.2±3.4 kJ mol⁻¹. A schematic mechanism of the reaction is proposed.

Keywords:

• α‐Methyldopa
• kinetic method
• determination
• spectrophotometric
• pharmaceutical preparations

The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP, and to Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, for financial support.