Extractive alkylation of 5,2′-dichloro-4′-nitrosalicylanilide (niclosamide) for gas-liquid chromatographic analysis

Abstract

Niclosamide (5,2′-dichloro-4′-nitrosalicylanilide), formulated as the ethanolamine salt, is one of the most effective and widely used molluscicides for the control of snail vectors of schistosomiasis, a parasitic disease afflicting over 200 million people in more than 70 countries. This report details the development of a sensitive, specific analytical method for the evaluation of niclosamide formulations and assessment of the impact of residues on the environment. Efficient (>85%) phase-transfer, N,O-dimethylation of niclosamide and the synthesized 5-deschloro analog internal standard, followed by gas-liquid chromatographic separation and electron-capture detection, permits the determination of as little as 10 ppb analyte in fortified, stagnant water. Tetrabutylammonium chloride was the phase-transfer agent, while methyl iodide was the methylating agent of choice among four investigated.