A Quantitative Analysis of Memantine in Human Plasma Using Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry

Abstract

The aim of this study is to compare the single-dose oral bioavailability of memantine hydrochloride 10 mg tablets of Ranbaxy Laboratories Limited, with NAMENDA™ tablets (containing memantine hydrochloride 10 mg) of Forest Pharmaceuticals Inc. in healthy, adult, human subjects under fasting condition. The study was carried out as 2-way crossover design on 8 subjects in fasting and fed conditions. The plasma samples were obtained over a 72 h post dose in each period. Plasma memantine samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with positive ion electro spray ionization using multiple reactions monitoring (MRM). A sensitive, reproducible, accurate and validated LC-MS/MS method with limit of quantification (LOQ) 0.200 ng/mL was used to analyze memantine. Ln transformed AUC0-72and Cmaxwere assessed for bioequivalence using 90% confidence interval (CI). 90% confidence intervals for the ratio of test and reference (Ratio of least-squares mean) for ln-transformed AUC0-72and Cmaxwere within the regulatory acceptance criteria of 80-125%.

Simultaneous determination of memantine and amantadine in human plasma as fluorescein derivatives by micellar electrokinetic chromatography with laser‐induced fluorescence detection and its clinical application

“…LLE with diethyl ether 8, diethyl ether‐chloroform 10, n ‐hexane 13, 16, dichloromethane 15, toluene 17, 19, 20, and isoamyl alcohol in n ‐heptane 21 or the solid‐phase extraction method 11 were used for the pretreatment of memantine or amantadine in the biological samples. In the study, we used LLE as the clean‐up method and compared different organic solvents on the efficiency of extraction.…”

“…The CE method with indirect detection using an absorbing background electrolyte was developed 7. LC‐MS 8–11 has been used for the direct determination of amantadine or memantine. To increase the sensitivity sufficiently to detect the concentration of biological samples, the samples were extracted with organic solvent and derivatized with labeling agents, then analyzed by GC‐MS 12, 13 or HPLC 14–21.…”

A new HPLC method with fluorescence detection for the determination of memantine in human plasma

“…The analysis of ME in human plasma is complicated, because the molecule cannot be quantified by the more readily accessible technique such as HPLC with UV–visible or fluorescence detection. The main advantage of the method is the ability to determine ME in plasma with a cheaper HPLC with fluorescence detector than mass detector 8–16. Also, the method has some advantages over the previously published methods based on derivatization reaction 4–7.…”

“…Other published methods for the ME in human plasma 4, rat plasma 5, 6 and in urine 7 involved liquid chromatography with fluorescence detection after pre‐column derivatization. All other recently developed liquid chromatographic or gas chromatographic methods for the quantification of ME in plasma are based on mass detection 8–16. Therefore, it is very imperative to develop a simple and suitable analytical method for the measurement of ME in plasma.…”

High‐performance liquid chromatographic determination of memantine hydrochloride in rat plasma using sensitive fluorometric derivatization

“…The assay of tricyclic amines is always performed using precolumn [4,[10][11][12] derivatization methods, or other detections, MS [13,14]. And memantine hydrochloride also has been determined by GC-MS [15] and UPLC [16].…”