Mise au point d’une méthode de dosage de l’hydroxycarbamide dans des préparations magistrales à usage pédiatrique.

Abstract

Hydroxyurea is an antineoplastic antimetabolite agent. It mainly acts by inhibiting the enzyme ribonucleotide reductase, leading to a halt in cell proliferation. The difficulty in swallowing the existing oral forms on the market (Hydrea) by children necessitates the development of a new adapted galenic form, whose safety and efficacy must be guaranteed by rigorous quality control based on an optimized analytical method. In this text, we undertook an experimental study aimed at developing and optimizing a method for the dosage of hydroxycarbamide by high-performance liquid chromatography (HPLC), based on definitive screening designs. The selected factors were the composition of the mobile phase (expressed as a percentage of Methanol) and the elution flow rate. The retention time of hydroxycarbamide and the resolution between adjacent peaks (hydroxycarbamide peak and excipient) were the evaluated responses. The results confirmed that the mobile phase flow rate has the most significant influence on the retention time of hydroxycarbamide. For the resolution, it was significantly influenced by the flow rate and the mobile phase composition; the optimal conditions corresponded to 7% methanol and a flow rate of 0.8 mL/min. A MODR allowed for the definition of a robust design space, within which an experimental point is selected (flow rate: 0.65 mL/min and methanol percentage: 6%) to ensure the stability and reliability of the method during routine use.