NDMA formation by chloramination of ranitidine: Kinetics and mechanism

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 monochlor...

Full description

Bibliographic Details
Main Authors: Roux, J., Gallard, H., Croué, Jean-Philippe, Papot, S., Deborde, M.
Format: Journal Article
Published: American Chemical Society 2012
Online Access:http://hdl.handle.net/20.500.11937/50189
_version_ 1848758416766402560
author Roux, J.
Gallard, H.
Croué, Jean-Philippe
Papot, S.
Deborde, M.
author_facet Roux, J.
Gallard, H.
Croué, Jean-Philippe
Papot, S.
Deborde, M.
author_sort Roux, J.
building Curtin Institutional Repository
collection Online Access
description 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.
first_indexed 2025-11-14T09:43:39Z
format Journal Article
id curtin-20.500.11937-50189
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T09:43:39Z
publishDate 2012
publisher American Chemical Society
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-501892017-09-13T15:40:43Z NDMA formation by chloramination of ranitidine: Kinetics and mechanism Roux, J. Gallard, H. Croué, Jean-Philippe Papot, S. Deborde, M. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/50189 10.1021/es3023094 American Chemical Society restricted
spellingShingle Roux, J.
Gallard, H.
Croué, Jean-Philippe
Papot, S.
Deborde, M.
NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title_full NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title_fullStr NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title_full_unstemmed NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title_short NDMA formation by chloramination of ranitidine: Kinetics and mechanism
title_sort ndma formation by chloramination of ranitidine: kinetics and mechanism
url http://hdl.handle.net/20.500.11937/50189