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

Paraskevas D Tzanavaras,Sofia Papadimitriou,Constantinos K Zacharis

doi:10.3390/molecules24213975

Paraskevas D Tzanavaras, Sofia Papadimitriou + Show 1 more

Open Access

https://doi.org/10.3390/molecules24213975

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Abstract

A zone-fluidics (ZF) based automated fluorimetric sensor for the determination of pharmaceutically active adamantine derivatives, i.e., amantadine (AMA), memantine (MEM) and rimantadine (RIM) is reported. Discrete zones of the analytes and reagents (o-phthalaldehyde and N-acetylcysteine) mix and react under stopped-flow conditions to yield fluorescent iso-indole derivatives (λex/ λem = 340/455 nm). The proposed ZF sensor was developed and validated to prove suitable for quality control tests (assay and content uniformity) of commercially available formulations purchased from the Greek market (EU licensed) and from non-EU web-pharmacies at a sampling rate of 16 h−1. Interestingly, a formulation obtained through the internet and produced in a third—non-EU—country (AMA capsules, 100 mg per cap), was found to be out of specifications (mean assay of 85.3%); a validated HPLC method was also applied for confirmatory purposes.

Highlights

Adamantane analogues namely amantadine (AMA) and rimantadine (RIM) have been extensively used for the treatment of influenza A virus infection for more than three decades [1,2]
Preliminary experiments confirmed that the analytes can react with OPA through their primary amino group under flow conditions, in the presence of a suitable nucleophilic agent (NAC) (Figure S2 in the supplementary material)
It was interesting to notice that despite the structure similarities of the analytes, RIM showed a considerably higher reactivity in both terms of reaction speed and sensitivity, due to the fact that the primary amino group is attached to a ternary carbon atom

Summary

Introduction

Adamantane analogues namely amantadine (AMA) and rimantadine (RIM) have been extensively used for the treatment of influenza A virus infection for more than three decades [1,2]. Due to the evolution of WEB drug suppliers and the existence of fake products in the market, the QC of commercially available pharmaceuticals is even more critical. On this basis, automation of the analytical process offers significant advantages in terms of rapidity and effectiveness [7]

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Conclusion