Automated Stopped-Flow Fluorimetric Sensor for Biologically Active Adamantane Derivatives Based on Zone Fluidics

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Sensor Technology

Background:

• Adamantane derivatives such as amantadine, memantine, and rimantadine are crucial pharmaceutical agents.
• Accurate quality control is essential for ensuring the safety and efficacy of these medications.
• Existing analytical methods may require significant sample preparation or specialized equipment.

Purpose of the Study:

• To develop and validate a zone-fluidics (ZF) based automated fluorimetric sensor for the determination of amantadine, memantine, and rimantadine.
• To assess the sensor's suitability for quality control testing of pharmaceutical formulations.
• To investigate the quality of commercially available adamantane derivative formulations from various sources.

Main Methods:

• Development of a zone-fluidics system utilizing stopped-flow conditions for analyte-reagent mixing.
• Fluorimetric detection of fluorescent iso-indole derivatives formed by the reaction of adamantane derivatives with o-phthalaldehyde and N-acetylcysteine.
• Validation of the sensor for assay and content uniformity tests.
• Comparison with a validated High-Performance Liquid Chromatography (HPLC) method.

Main Results:

• The ZF sensor successfully determined amantadine, memantine, and rimantadine with a sampling rate of 16 h⁻¹.
• The sensor was validated for quality control of pharmaceutical formulations.
• An amantadine capsule formulation obtained from a non-EU web-pharmacy was found to be out of specification (85.3% mean assay).
• HPLC analysis confirmed the out-of-specification result.

Conclusions:

• The automated ZF fluorimetric sensor offers a reliable and efficient method for the quality control of adamantane derivatives.
• The sensor is suitable for routine pharmaceutical analysis, including assay and content uniformity.
• The study highlights potential quality issues with certain online pharmaceutical sources, emphasizing the need for rigorous testing.