Stability study of an oral solution with arginine, citrulline and biotin used for the treatment of pediatric metabolic disease

SALVO L.; LUCANGIOLI S.; TRIPODI V.; DOBRECKY C.; BUOMTEMPO F.; FLOR S

CIUDAD DE MEXICO

Simposio; 23 th Latin-American Symposium on Biotechnology, Biomedical, Biopharmaceutical and Industrial Applications of Capillary Electrophoresis and Microchip Technology; 2017

LACE

Citrulline, and Arginine are used in the treatment of urea cycle disorders and Biotin in biotinidase deficits. In addition, the two amino acids and biotin can be used in hyperammonemia for the management of alterations in amino acid metabolism. So far, there is not a commercial formulation of those three actives together, especially for pediatric patients. From a physicochemical point of view, these molecules pose an analytical challenge.The aim of this work was to develop a fast and simple method by capillary zone electrophoresis for the simultaneous quality control and stability studies of an orphan formulation of arginine, citrulline and biotin manufactured in our lab. The electrophoretic conditions were: a capillary of 60 cm (75 µm id), -10 kV, direct UV detection at 195 nm and the BGE consisted of 40 mM pH 2.5 Tris buffer.The developed method was validated according to ICH guidelines, in terms of linearity, LOD and LOQ, precision, accuracy and selectivity, and showed to be suitable for the quality control and stability studies. Linearity of arginine, citrulline and biotin was demonstrated in a range from 10.0 to 1000.0 μg/mL with a r2 0.9808, with LODs between 0.30 and 1.0 and LOQs between, 1.0 and 3.3 µg/mL. Intra and interday precision were evaluated and RSD values were below 2.0 and also, accuracy expressed as percentage of recovery was between 99.0 and 101.9 for the three levels for the three analytes. This method is suitable for the quality control and stability study in pharmaceutical formulations.