Розробка та валідація ВЕРХ-МС методики визначення мемантину гідрохлориду для вивчення профілів розчинення

Abstract

A method for quantitative determination of memantine hydrochloride by HPLC with mass spectrometric detection (HPLC-MS), suitable for the study of dissolution profiles of tablets "Mematon IС" was developed. Chromatographic determination was performed using a mobile phase of methanol - 0.1% (v/v) aqueous solution of formic acid (55:45) on a column of Zorbax Eclipse Plus C18 size 10 cm Ч 4.6 mm (3.5 μm) at a flow rate of 1 ml/min. The linearity interval in the appropriate dissolution media is 35 - 150 % of the normalized content of memantine hydrochloride in the tablet. The method is validated on the parameters of specificity, accuracy, correctness, linearity in the studied range of concentrations, robustness. The stability of the tested solutions and reference solutions in the case of their storage at room temperature for 24 hours was confirmed. It is established that in the case of the study of solutions prepared in a dissolution medium of 0.1 M hydrochloric acid solution pH 1.2, there is a need to preneutralize hydrochloric acid before analysis, because it, as stronger than formic acid, almost completely ionizes all dissolved molecules, which leads to a significant deviation of the linear dependence of the analytical signal on the concentration of the analyte. Neutralization is performed with 0.1 M sodium hydroxide solution, which is added to the sample of the test solution. The release of more than 85 % of memantine hydrochloride in 15 min in all dissolution media indicates the similarity of the dissolution profiles and does not require the calculation of the similarity factor f2.