Quantitative trace analysis of a broad range of antiviral drugs in poultry muscle using column-switch liquid chromatography coupled to tandem mass spectrometry

Abstract

A liquid chromatography–tandem mass spectrometry method for the analysis of seven antiviral drugs, zanamivir, ribavirin, oseltamivir, oseltamivir carboxylate, amantadine, rimantadine and arbidol, in poultry muscle is reported. The antiviral drugs were extracted from the homogenized poultry muscle sample using methanol. The extract was purified using tandem solid-phase extraction combining a cation exchange cartridge and a phenylboronic acid cartridge. To prevent excessive matrix effects, the analytes were separated from the matrix constituents using a column-switch liquid chromatography system combining a reversed-phase and a Hypercarb analytical column. Detection was carried out using tandem mass spectrometry. The method was fully validated according to 2002/657/EC [1] and proved to be adequate for quantification and confirmation of zanamivir and ribavirin at 10 μg kg−1, oseltamivir, oseltamivir carboxylate, amantadine and rimantadine at levels below 1.0 μg kg−1 and for qualitative confirmatory analysis of arbidol at levels below 1 μg kg−1.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-011-5581-3) contains supplementary material, which is available to authorized users.

Characterization and Physicochemical Evaluation of Molecular Complexes Formed Between Umifenovir and Dicarboxylic Acids

“…The situations where ∆pK a (the pK a difference between the base and acid) is larger than 3 almost exclusively result in salt formation, while situations with ∆pK a <0 almost exclusively result in cocrystal formation, but 0<∆pK a <3 can lead to either salts or co-crystals, or even complexes with partial proton transfer, with the location of the acidic proton dependent on the specific crystal packing environment [17]. Table 1 presents the ΔpK a values calculated from the pK a values of umifenovir and dicarboxylic acids given in the literature [18]. …”

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

“…Arbidol is a relatively strong base with the pKa value equaling 6.0 (for the dimethylamino group) [27]. It is widely accepted in the literature that whether an API and a guest molecule form a salt or cocrystal can be predicted in terms of the ∆pKa rule (ΔpKa = pKa (base) − pKa (acid) ) [28][29][30].…”

“…As it has been mentioned, Arb is a relatively strong base with pKa value near 6.0 [27]. Therefore, the solubility of the drug, as well as its salts, in aqueous solutions is expected to be pH-dependent.…”

Potential impacts of climate change on veterinary medicinal residues in livestock produce: An island of Ireland perspective††This paper is one of a series of reviews on “Climate Change and Food Safety – an Island of Ireland perspective”.

“…(WHO, 2005). Analytical methods have been developed to test for residues of some antiviral drugs in poultry meat (Berendsen et al, 2012), but widespread adoption of antiviral drugs by livestock industries has thus far been averted. Residues of antiviral drugs do not currently form a part of routine residues testing plans in Europe.…”