Comprehensive headspace gas chromatographic analysis of denaturants in denatured ethanol.

To discourage consumption, ethanol is often denatured using both volatile (e.g., methyl ethyl ketone and isopropanol) and nonvolatile (e.g., denatonium benzoate) chemical substances. As a result, the analysis of denatured ethanol samples is usually performed by multiple techniques such as gas chromatography for the volatile denaturants and liquid chromatography for the nonvolatile ones. However, the need for multiple techniques increases the cost of analysis and forms a severe obstruction for on-site product control. Using the full evaporation technique combined with gas chromatography and flame ionization detection, only one analytical methodology has to be used here to determine both volatile and nonvolatile denaturants in denatured ethanol. Denatonium benzoate is determined as benzyl chloride following an in-vial reaction. Compared to conventional techniques, the novel method performs equally well, but it is simpler to apply. At the same time, drawbacks of alternative methods are circumvented such as equilibration issues and alterations to the stationary phase when using liquid chromatography with ion pairing agents or matrix effects when applying static headspace gas chromatography. The developed method showed good linearity, repeatability, and recovery toward all analytes and was applied to the analysis of commercial denatured ethanol for disinfection and ethanol-based windscreen washer fluids.

Headspace gas chromatography based methodology for the analysis of aromatic substituted quaternary ammonium salts.

The analysis of quaternary ammonium salts (QAS) using GC is often performed by "in injector" pyrolysis to create volatile degradation products for quantification purposes. Besides the risk of severe system contamination, the application of this approach on aqueous samples is problematic. In this work, the sample is treated in a vial with 2,2-dimethoxypropane (DMP) under acidic catalysis. In addition to the removal of water and sample enrichment, the QAS are decomposed. As HS 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. All these can be used as an analytical target. A calibration curve for benzyl chloride could be derived from the pure compound. Chloromethane 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 QAS under investigation was close to 100%. The presented procedure allows the quantification of any aromatic substituted QAS without the need for a matching reference, which is a major advantage over existing CE and LC methods 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 approach provided excellent linearity (R2≥0.999) and limits of detection around 0.01µg/vial for benzyl chloride. 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. Treating those samples in the vial with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) after the enrichment step removes the interference and leaves a possible pathway for the simultaneous determination of glycerol in those samples.

Application of acetone acetals as water scavengers and derivatization agents prior to the gas chromatographic analysis of polar residual solvents in aqueous samples.

The sensitivity of gas chromatography (GC) combined with the full evaporation technique (FET) for the analysis of aqueous samples is limited due to the maximum tolerable sample volume in a headspace vial. Using an acetone acetal as water scavenger prior to FET-GC analysis proved to be a useful and versatile tool for the analysis of high boiling analytes in aqueous samples. 2,2-Dimethoxypropane (DMP) was used in this case resulting in methanol and acetone as reaction products with water. These solvents are relatively volatile and were easily removed by evaporation enabling sample enrichment leading to 10-fold improvement in sensitivity compared to the standard 10µL FET sample volumes for a selection of typical high boiling polar residual solvents in water. This could be improved even further if more sample is used. The method was applied for the determination of residual NMP in an aqueous solution of a cefotaxime analogue and proved to be considerably better than conventional static headspace (sHS) and the standard FET approach. The methodology was also applied to determine trace amounts of ethylene glycol (EG) in aqueous samples like contact lens fluids, where scavenging of the water would avoid laborious extraction prior to derivatization. During this experiment it was revealed that DMP reacts quantitatively with EG to form 2,2-dimethyl-1,3-dioxolane (2,2-DD) under the proposed reaction conditions. The relatively high volatility (bp 93°C) of 2,2-DD makes it possible to perform analysis of EG using the sHS methodology making additional derivatization reactions superfluous.

Evaluation of the full evaporation technique for quantitative analysis of high boiling compounds with high affinity for apolar matrices.

In order to reduce inaccuracies due to possible matrix effects in conventional static headspace-gas chromatography (sHS-GC), it is standard practice to match the composition of calibration standards towards the composition of the sample to be analysed by adding blank matrix. However, the latter is not always available and in that case the full evaporation technique (FET) could be a solution. With FET a small sample volume is introduced in a HS vial and compounds of interest are completely evaporated. Hence no equilibrium between the condensed phase and vapour phase exists. Without the existence of an equilibrium, matrix effects are less likely to occur. Another issue often encountered with sHS-sampling is that low vapour pressure compounds with a high affinity for the dilution medium show a limited sensitivity. FET has proven to be an appropriate solution to address this problem too. In this work, the applicability of FET for the quantitative analysis of high boiling compounds in different complex apolar matrices is examined. Data show that FET is an excellent tool to overcome matrix effects often encountered with conventional sHS analysis. The tested method shows excellent accuracy with recovery values around 100% as well as repeatability with RSD values around 1% for the quantification of high boiling compounds (bp>200°C) such as camphor, menthol, methyl salicylate and ethyl salicylate in various matrices. LOQ values were found to be around 0.3µg per vial. Following validation of the technique, several topical pharmaceutical formulations like ThermoCream(®), Reflexspray(®), Vicks Vaporub(®) and Radosalil(®) were examined. For the latter, a comparison has been made with a sHS-method described in literature.