Sensitive and Rapid HPLC Method for Determination of Memantine in Human Plasma Using OPA Derivatization and Fluorescence Detection: Application to Pharmacokinetic Studies

Afshin Zarghi

doi:10.3797/scipharm.1008-17

Abstract

A rapid, sensitive and reproducible HPLC method was developed and validated for the analysis of memantine in human plasma after derivatization with o-phthaldialdehyde (OPA) and fluorescence detection. Amantadine was used as internal standard. The derivatized memantine and amantadine were eluted in less than 10 min with no interference from endogenous plasma peaks. The analysis was carried out on a monolithic silica column (Chromolith Performance RP-18e, 100×4.6 mm). The mobile phase was composed of a mixture of acetonitrile and 0.025 M phosphate buffer (50:50, v/v, pH=4.6) with a flow rate of 2.5 mLmin−1. The excitation and emission wavelengths were set at 335 nm and 440 nm respectively. The assay enables the measurement of memantine for therapeutic drug monitoring with a lower quantification limit of 2 ngmL−1. The method involves simple extraction procedure and analytical recovery was 82.8± 0.9%. The calibration curve was linear over the concentration range 2–80 ngmL−1. The coefficients of variation for inter-day and intra-day assay were found to be less than 8%. The method was successfully applied to pharmacokinetic studies in humans.

Highlights

Memantine (I, Fig. 1), 1-amino-3,5-dimethyladamantane hydrochloride, is an adamantine derivative administered orally for many neurologic disorders, including Alzheimer's disease and Parkinson [1,2,3,4]
The present study describes a rapid and sensitive HPLC method based on derivatization with o-phthaldialdehyde (OPA) with fluorescence detection, which enables the determination of memantine with good accuracy at low drug concentrations in plasma using simple extraction procedure
Separation was performed on a reversed-phase monolithic column, which has lower separation impedance comparing to the particulate packings, and it allows easy optimizing chromatographic conditions to obtain desirable resolution in a short time

Summary

Introduction

Memantine (I, Fig. 1), 1-amino-3,5-dimethyladamantane hydrochloride, is an adamantine derivative administered orally for many neurologic disorders, including Alzheimer's disease and Parkinson [1,2,3,4]. Memantine is readily absorbed from the gastro-intestinal tract with peak concentrations in plasma occurring ranges from 3 to 8 hours after administration by mouth It is poorly metabolized by the liver and about 70% of the administered dose excreted, unchanged, in the urine. LC methods based on MS or MS-MS as the detection system for the analysis of memantine in plasma are very sensitive, having low quantitation limits. These methods are not available for most laboratories because of their specialty requirement and financial reasons. The present study describes a rapid and sensitive HPLC method based on derivatization with o-phthaldialdehyde (OPA) with fluorescence detection, which enables the determination of memantine with good accuracy at low drug concentrations in plasma using simple extraction procedure. We demonstrate the applicability of this method for pharmacokinetic studies in humans

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