LUMINESCENT DETERMINATION OF FAVIPIRAVIR USING THE EUROPIUM (III) COMPLEX

Abstract

Of particular interest in recent years is the possibility of analytical application not only of the effects of sensitizing the luminescence of lanthanide ions, but also its quenching or increase for the indirect determination of a number of drugs. Favipiravir (FAV) - 6-fluoro-3-hydroxypyrazine-2-carboxamide - is an oral antiviral drug approved for the treatment of influenza in Japan. This drug is an analogue of purine nucleosides, which acts as a competitive inhibitor of RNA polymerase required for virus replication.
 Favipiravir is capable of forming a complex compound with Eu(III) ions, in which due to intramolecular transfer of excitation energy from the organic ligand to the Eu(III) ion there is a very slight sensitized luminescence of the latter due to dissipation of excitation energy from the triplet level (24390 cm-1), which cannot be used for analytical purposes.
 The influence of some surfactants and donor-active substances on the Ilum of the Eu(III) –FAV complex is considered. It was found that only batophenanthroline (BPh) significantly increases the luminescence intensity (Ilum) of the Eu(III)–FAV complex, approximately 10 times, due to more efficient intramolecular energy transfer from batophenanthroline (18100 cm-1) to the level of europium ions (17300 cm-1). A synergistic effect has been established, which is manifested in the combined action of two complexes (Eu(III)–BPh and Eu(III)–FAV) and exceeds the sum of the Ilum of each of them separately. The synergism is caused by formation of a multiligand complex. It was established that a mixed ligand complex Eu(III)–BPh–FAV (1:1:1) is formed.
 The possibility of using the complex compound Eu(III)-BPh as a new luminescent probe for the determination of favipivir has been shown. The luminescence intensity is maximum at pH 7.5 (urotropin buffer). The excitation band λexc = 315 nm was chosen for analytical purposes. It was found that the introduction of different amounts of favipiravir into aqueous solutions of the Eu(III)-BPh complex causes an increase in 4f-luminescence of europium (III) (transition 5D0 → 7F2, λemis = 615 nm) and the lifetime of its excited state.
 Calibration curve was linear over the concentration range of favipivir 0.5-10.0 μg/ml. The developed method is validated by the following parameters: specificity, linearity, accuracy, limit of quantitative determination. The proposed method is characterized by satisfactory metrological characteristics and ease of implementation and can be recommended for the determination of FAV in tablets.