NDMA formation by chloramination of ranitidine: kinetics and mechanism.

Julien Le Roux, Hervé Gallard, Jean-Philippe Croué, Sébastien Papot, Marie Deborde

Université de Poitiers - CNRS, UMR 7285 IC2MP - ENSIP, 1 rue Marcel Doré, 86022 Poitiers Cedex, France.

Environmental science & technology 2012 Oct 16

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The kinetics of decomposition of the pharmaceutical ranitidine (a major precursor of NDMA) during chloramination was investigated and some decomposition byproducts were identified by using high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The reaction between monochloramine and ranitidine followed second order kinetics and was acid-catalyzed. Decomposition of ranitidine formed different byproducts depending on the applied monochloramine concentration. Most identified products were chlorinated and hydroxylated analogues of ranitidine. In excess of monochloramine, nucleophilic substitution between ranitidine and monochloramine led to byproducts that are critical intermediates involved in the formation of NDMA, for example, a carbocation formed from the decomposition of the methylfuran moiety of ranitidine. A complete mechanism is proposed to explain the high formation yield of NDMA from chloramination of ranitidine. These results are of great importance to understand the formation of NDMA by chloramination of tertiary amines.

Citation

Julien Le Roux, Hervé Gallard, Jean-Philippe Croué, Sébastien Papot, Marie Deborde. NDMA formation by chloramination of ranitidine: kinetics and mechanism. Environmental science & technology. 2012 Oct 16;46(20):11095-103