LC‐MS ion maps for the characterization of aniline derivatives of fatty acids and triglycerides in laboratory‐denatured rapeseed oil

Abstract

In 1981 Spain went through a unique epidemic associated with a food-borne vector, affecting more than 20 000 people with over 800 deaths, which came to be known as the Toxic Oil Syndrome (TOS). Early epidemiological studies showed a link between this illness and the ingestion of rapeseed oil denatured with 2% aniline. This oil, originally aniline-denatured for industrial use, was fraudulently processed in an attempt to remove free aniline, and marketed as edible oil. Fatty acid anilides (FAA), monoesters and diesters of 3-(N-phenylamino)-1,2-propanediol (PAP) are present in oil samples as they arise in the refining process from reactions of aniline with constituent fatty acids and triglycerides of the oil matrix and are the only extraneous compounds found in these samples. To expand the search for the causative agents in TOS-associated oils and to look for new aniline-related compounds, an exhaustive characterization of laboratory-processed oils was undertaken. These oils, in the presence of aniline doped with 14 C labelled aniline, were submitted to the laboratory conditions required for the generation of PAPs and FAAs. Laboratory-generated oil samples were submitted to a liquid-liquid extraction procedure to remove the unreacted aniline. The extract was processed by double solid-phase extraction to improve detection limits for minor amine-containing compounds in oils. The extracts enriched in aniline derivatives were submitted to on-line HPLC-UV-APCI-MS. Using two-dimensional ion maps, the components of several families of derivatives were readily identified. Additionally, the extracts were also fractionated by HPLC-UV and the fractions were analyzed by HPLC-APCI-MS/MS to obtain structural information. Standards of some of these compounds were synthesized and analyzed to confirm the results. A total of 115 aniline derivatives from 9 aniline-related families were identified in these oil samples. These included fatty acid anilides and an extensive array of phenylaminopropanediol esters distributed in eight major compound classes.

Advances in structure elucidation of small molecules using mass spectrometry

“…These ion maps can be obtained by a longer direct infusion process with autosamplers or better by nanoESI using Nanomate (Advion Inc.) robotic injections to allow long-enough scan times. The method should not be confused with spatial ion maps obtained from secondary ion mass spectrometry TOF-SIMS [200] or mass spectrometric imaging or ion maps that refer to retention time– m/z visualizations (LC-MS ion maps) [201]. The total ion map is a function of precursor m/z value versus product ion m/z value and intensity, and it can be represented in two- or three-dimensional space.…”

Food Contamination

“…43 Toxic oil syndrome is a unique combination of vasculitis, thrombosis, and immunologic changes (e.g., T -lymphocyte activation, cytokine release) that differs from the toxicity previously associated with refi nery products, additives, or contaminants. In a study of toxic oil syndrome -associated oils, fractionation of the oils by high performance liquid with ultraviolet detection (HPLC/UV) and analysis by high performance liquid chromatography/atmospheric pressure chemical ionization/ tandem mass spectrometry (HPLC/ APCI/MS/MS) demonstrated 115 aniline derivatives from nine aniline -related families of chemicals.…”

Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed‐Phase UPLC Method for its Genotoxic/Aniline Impurity

“…A genotoxic activity of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats was reported 10 by Ernst and Bernd. Potent genotoxicity of aminophenylnorharman, formed from aniline in the liver of gpt delta transgenic mouse was reported 11 by Ken-ichi Masumura et al Carcinogenicity of aminophenylnorharman, formed from aniline in F344 rats had been reported 12 by Toshihiko Kawamori et al A few analytical methods has also been reported for quantification of aniline such as spectrometric 13 , azo-dye formation 14 , fluorescence 15,16 , alternating-current oscillopolarographic titration 17 , NIR spectroscopy 18 , GC 19 , HPLC 20,21 and LCMS 22,23 .…”