DEVELOPMENT AND VALIDATION OF STABILITY INDICATING GREEN HPLC-PDA METHOD FOR DETERMINATION OF HYDROXYUREA

Hydroxyurea (HU) is the therapeutic class of antimetabolites and acts on the cell cycle by inhibiting the ribonucleotide reductase enzyme present in DNA (deoxyribonucleic acid) biosynthesis and maintaining it in the S phase. This drug is used in the treatment of neoplastic diseases such as myeloid leukemia, psoriasis and has recently shown great clinical efficacy in the treatment of sickle cell disease, being the only drug capable of reducing vaso-occlusive effects and improving the quality of life of patients. Despite the clinical importance of HU, the Brazilian Pharmacopoeia 5th edition (2010) does not present a monograph intended for this drug, nor does it exist in the scientific literature and official compendiums stability indicanting analytical methods (SIAM) for HU. The development and validation of analytical methods for this molecule are justified by its therapeutic potential and by the need for methods that prove its quality, with agility, low cost and low environmental impact. In this work the quantative analysis of the HU in bulk and pharmaceutical form was carried out by high performance liquid chromatography with photodiode array (HPLC-PDA). For the stability indicating analytical method (SIAM), a chromatographic study was carried out with Phenomenex® C18 (250 x 4.6 mm, 5 μm); the mobile phase was composed by water and ethanol (95:05, v/v) in isocratic mode. The flow rate was 0.5 mL/min and the wavelength setted at 214 nm. The SIAM for the quantification of HU was selective, linear, precise, accurate, sensitive and robust and comply with national and international quality requirements.