DETERMINATION OF THE INFLUENCE OF BORATE ION ON THE DEGRADATION OF L-α-METHYLDOPA USING RP-HPLC WITH PHOTODIODE ARRAY DETECTION

Abstract

The degradation of the drug L-α-methyldopa (MD) in alkaline solutions was studied by Reversed-Phase High Performance Liquid Chromatography. It was found that the presence of borate ion in the solution inhibited the formation of MD-melanin, the final product of degradation. It complexes with both MD and intermediates of the pathway, maintaining them longer in the medium. Through the use of a synthetic standard of a half-way intermediate of the oxidation pathway, 5,6-dihydroxy-2-methylindole (Me-DHI), and examination of the UV/vis spectra of the chromatographic peaks, it was possible to demonstrate the stabilization of a later stage degradation intermediate in the presence of borate ion.

The inhibition of melanin formation may be correlated to the stabilization of this intermediate. Hence, this mechanism could be generalized and applied to biogenic catecholamines, such as dopamine and L-dopa, the natural precursor of mammalian melanin.

ACKNOWLEDGMENTS

This work was supported in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico. The Fundção Oswaldo Cruz and the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro are also acknowledged for the grant conceded to P. R. The authors are grateful to Dr. Rosane A. San Gil and Dr. Benjamin Gilbert for reading the manuscript.