HTC-15 - Abstract

Abstract Title: Analysis of Aromatic Substituted Quaternary Ammonium Salts using a Headspace Gas Chromatography Based Methodology
Abstract Type: Poster
Session Choice: Hyphenated Techniques for Comprehensive Analysis
Presenter Name: Prof Erwin Adams
Co-authors:Dr Niels van Boxtel
Ms Marta Guillen Palacin
Prof Ann Van Schepdael
Mr Juan Aspromonte
Mr Kris Wolfs
Company/Organisation: Pharmaceutical Analysis - KU Leuven
Country: Belgium

Abstract Information :

The quantitative analysis of quaternary ammonium salts (QAS) using gas chromatography (GC) is often performed by "in injector" pyrolysis to create volatile degradation products. Besides the risk of severe system contamination, the application of this approach on samples containing a large amount of water is problematic. In this work, samples are treated in a vial with 2,2-dimethoxypropane (DMP) under acidic catalysis. During this process, water is removed, the sample is enriched and the QAS are decomposed. As a headspace (HS) sampler transfers only volatile compounds to the GC system, contamination is avoided.

It was found that depending on the presence of benzyl, phenyl or methyl groups on the quaternary nitrogen; benzyl chloride, N,N-dimethylaniline or chloromethane are formed respectively in the sealed vial. Quantification was performed through benzyl chloride (as major volatile degradation product) and chloromethane. For benzyl chloride, the pure compound could be used to construct the calibration line. Chloromethane was not available as such and was generated from pure benzyldimethyldecylammonium chloride (BEDIDE), a pure QAS with benzyl and methyl groups, to construct a secondary calibration curve using a back analysis approach. It has been proven that by quantifying the formed analytical targets, the mass balance for the studied QAS was close to 100%. The presented approach allows the quantification of any aromatic substituted QAS without the need for a matching reference, which is a major advantage over existing methods using mostly liquid chromatography or capillary electrophoresis.

The proposed methodology was validated for mouth sprays containing benzethonium chloride (BZTCl) or benzoxonium chloride (BZOCl) and for denatonium benzoate (DB) in ethylene glycol (EG) based cooling liquids. Results showed that the proposed procedure provided excellent linearity (R2 ≥ 0.999), recovery values around 100%, good repeatability with RSD-values not exceeding 2.5% and a detection limit for benzyl chloride around 0.01 µg/vial. It was found that the reaction product of DMP and glycerol (which was also present in the mouthspray and some cooling liquids) caused chromatographic interference with benzyl chloride. Silanisation of those samples after the enrichment step removes this interference and leaves a possible pathway to determine glycerol simultaneously.