Xavier Cahours

Microemulsion electrokinetic chromatography versus capillary electrochromatography-UV-mass spectrometry for the analysis of flunitrazepam and its major metabolites.

Benzodiazepines, namely flunitrazepam and its three major metabolites, were successfully separated by microemulsion electrokinetic chromatography. Separation was achieved using an untreated fused‐silica capillary (48 cm (effective length 40 cm) × 50 νm) at 25 kV; detection was performed by UV at 220 nm. The microemulsion system consisted of 70 mM octane, 800 mM 1‐butanol, 80 mM sodium dodecyl sulfate (SDS) and 10 mM borate buffer, pH 9. Very high efficiencies (up to 400 000 plates) and resolution better than 3 were achieved. Since this technique is not compatible with mass spectrometry (MS) detection, a capillary electrochromatographic (CEC) method was developed to separate flunitrazepam and its metabolites. The effects of mobile phase composition and pH as well as voltage and temperature were systematically investigated. The optimized CEC method allowed the baseline separation of the investigated compounds. For the on‐line coupling of CEC with electrospray ionization‐mass spectrometry, the column was connected to a void fused‐silica capillary using a Teflon connection. This configuration was found efficient and suitable for hyphenation of commercial CEC and MS instrumentation using commercially available CEC columns.

Simultaneous analysis of polyhydroxylated alkaloids by capillary electrophoresis using borate complexation and evaluation of sweeping technique for sensitivity improvement

SummaryCapillary zone electrophoresis coupled to UV detection was used for the simultaneous analysis of naturally occurring polyhydroxylated alkaloids. This separation was based on anin-situ complexation with borate ions. The effect of parameters such as borate concentration, capillary temperature and analyte molecular structure on migration times and selectivity were discussed. The best separation was obtained with a fused silica capillary (48.5 cm total length ×50 μm I.D., with a bubble factor of 3), 80 mM sodium tetraborate aqueous solution at pH 9.2 and temperature of 20°C. The method was validated and showed good data in terms of migration time and peak area reproducibility, selectivity, linearity and accuracy. The validated method was applied to determine miglitol in commercially available pharmaceutical tablets. To further improve method sensitivity, a sweeping technique involving borate ions was evaluated. This technique was found very sensitive to the analyte complexation with borate, borate concentration, and temperature as well as sample matrix. In the case of miglitol, a 35-fold improvement in peak height was achieved.

An Assessment of Indoor Air Quality before, during and after Unrestricted Use of E-Cigarettes in a Small Room

Airborne chemicals in the indoor environment arise from a wide variety of sources such as burning fuels and cooking, construction materials and furniture, environmental tobacco smoke as well as outdoor sources. To understand the contribution of exhaled e-cigarette aerosol to the pre-existing chemicals in the ambient air, an indoor air quality study was conducted to measure volatile organic compounds (including nicotine and low molecular weight carbonyls), polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines and trace metal levels in the air before, during and after e-cigarette use in a typical small office meeting room. Measurements were compared with human Health Criteria Values, such as indoor air quality guidelines or workplace exposure limits where established, to provide a context for potential bystander exposures. In this study, the data suggest that any additional chemicals present in indoor air from the exhaled e-cigarette aerosol, are unlikely to present an air quality issue to bystanders at the levels measured when compared to the regulatory standards that are used for workplaces or general indoor air quality.

Some consequences of using cigarette machine smoking regimes with different intensities on smoke yields and their variability

When smoking cigarettes under an intense regime with a combination of 100% ventilation blocking and high flow rates, as currently mandated by Health Canada, significant increases in filter temperatures and disproportionately high levels of mainstream smoke water and moisture accumulating in the spent filter were found when compared to other smoking regimes, especially for highly filter ventilated cigarettes. These effects have been reported to decrease cigarette firmness during the course of smoking, to alter filtration properties and efficiencies and to confound the measurement of particulate matter. The high filter temperatures generated also lead to significant amounts of vapour phase compounds desorbing from carbon filters and an over-estimation of the yields of these components. Less adsorption on or more desorption from carbon filters was found for compounds with the highest volatility. Therefore, yield data from the intense regime may not reflect the effectiveness of cigarette design features to reduce certain smoke components that occurs when products are smoked under conditions closer to those used by the majority of smokers in real world situations. In addition, a combination of these interacting factors may explain the worse level of between-laboratory reproducibility data for particulate matter measurement obtained during intense machine smoking. Among-laboratory data variability for vapour phase components, other than carbon monoxide, and for particulate phase components, other than nicotine, still needs to be evaluated in collaborative studies. Before proposing smoking regimes as tools to evaluate smoke emissions, it is essential to understand these various interacting factors and subsequent uncontrolled effects that such regimes can generate and the limitations of their use. These observations imply that higher tolerances may need to be set and taken into account when smoking under the intense regime before deciding that, for a given product, there are real differences between the yields determined in different laboratories.

Electronic cigarettes and indoor air quality: a simple approach to modeling potential bystander exposures to nicotine.

There has been rapid growth in the use of electronic cigarettes (“vaping”) in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents.

Effect of Sugar Content on Acetaldehyde Yield in Cigarette Smoke

Abstract The relationship between cigarette blend sugar and acetaldehyde formed in its smoke is a matter of current regulatory interest. This paper provides a re-analysis of data from 83 European commercial cigarettes studied in the 1970s and more modern data on sugar levels and acetaldehyde yields from a series of 97 European commercial cigarettes containing both inherent sugar and in other cases inherent and added sugar. It also provides data from 65 experimental cigarette products made from single curing grades of tobacco, having a wide range of inherent sugar levels but no added sugar. This study has shown that there is no relationship between acetaldehyde yields and blend sugar content even if a multivariate analysis is carried out taking into account Nicotine Free Dry Particulate Matter (NFDPM) as a co-factor. Such analyses should take into consideration each of the known contributory factors in order to avoid misleading conclusions. No distinction was found between the mainstream acetaldehyde yields from dark air-cured, flue-cured or US blended style cigarettes irrespective of their sugar content after taking account of differences in NFDPM yields. Similarly, no distinction was found between mainstream acetaldehyde yields of cigarettes made from single grades of either flue-cured, sun-cured or air-cured tobaccos with no sugar added. This work supports the conclusion that structural material in the tobacco plant is the main source of acetaldehyde in mainstream smoke after combustion during cigarette smoking.

High performance liquid chromatography of acarbose and its metabolite on porous graphitic carbon column

This paper describes the development of an analytical method for the determination of two pseudo-oligosaccharides, acarbose and its main metabolite. The analysis was carried out by liquid chromatography on a porous graphitic carbon stationary phase. The separation mechanism of these compounds is dominated by charge-induced interactions between the polar analyte and the polarizable surface of graphitic carbon. Several chromatographic parameters were investigated, including the nature and percentage of the organic solvent and acid modifier as well as column temperature. The best conditions were achieved with a mobile phase containing trifluoroacetic acid 0.1% and acetonitrile 8%. Under these conditions, the simultaneous resolution of acarbose and its metabolite as well as of their anomers was achieved, highlighting the potential of this stationary phase for challenging separations. Moreover, three detection methods are described and compared in terms of sensitivity. The evaporative light scattering detector was not sensitive enough for acarbose and metabolite determination in biological fluids. Mass spectrometry allowed a significant improvement in sensitivity but was not sufficient to permit the analysis of selected compounds in such complex matrices. However, this detector confirmed the presence of acarbose and its metabolite as well as the anomeric separation. Finally, fluorescence detection was found to be very sensitive after derivatization with 2-aminobenzamide and enabled the determination of selected compounds at a low concentration level.

Aspects of the design protocol and the statistical methods for analysis of tar, nicotine and carbon monoxide yields in cigarette smoke that can affect the measurement variability within collaborative studies.

Statistical principles described in ISO 5725-1 (1994) are a robust basis for evaluating cigarette smoke data from collaborative studies under the ISO 3308 machine smoking and for specifying the criteria for the removal of outlier data and determination of mean yields and their variability. However, the standard only provides recommendations on outlier removal that should be taken into account by experts who undertake data interpretation. The potential for over-interpretation of data from small numbers of laboratories is highlighted and recommendations made to deal with this possibility. Key variables to the statistical analysis, the number of cigarettes per replicate and replicates performed in each laboratory, the number of participating laboratories and the use of linear and rotary smoking machines in smoke collection, are identified and their relevance to obtaining robust data are considered. The statistical methods routinely used for data analysis from the ISO regime, are re-assessed for their suitability to analyse data obtained under the Canadian intense (CI) regime, where yield differences between linear and rotary smoking machines are found. This machine effect can lead to more outliers being detected and difficulties in outlier detection which may affect the provision of robust estimates of mean yields, repeatability and reproducibility.

An Experimental Method to Determine the Concentration of Nicotinein Exhaled Breath and its Retention Rate Following Use of an ElectronicCigarette

An experimental method is presented for the first time to determine the concentration of nicotine in exhaled breath following e-cigarette use in experienced participants and the impact that vaping topography has on the retention rate of nicotine. Aerosols from e-cigarettes containing different concentrations of nicotine were first evaluated by GC-FID to determine the concentration of nicotine delivered per puff versus machine - vaping intensity. These e-cigarettes were then vaped by participants through a cigarette holder attached to a smoking topography analyzer which recorded puff volume and puff duration. This allowed the concentration of nicotine in the aerosol inhaled by the participant during each puff to be determined. A PTR-MS instrument was then used to determine the concentration of nicotine exhaled following each use of the e-cigarette. By dividing this figure by the nicotine concentration delivered enabled its retention rate to be calculated. The principal finding was over 99% of the nicotine was retained by the participants when the e-cigarette aerosol was inhaled and a reduced but still substantial quantity was retained (on average 86%) when the e-cigarette aerosol was held in the mouth only (i.e, no inhalation). In both cases, the nicotine concentrations detected in the exhaled breath were low (range 1.8 - 1786 ppb). The experimental method presented here may be used to determine the concentration of other e-cigarette aerosol constituents in exhaled breath and the retention rate of those constituents which is useful for the evaluation of e-cigarettes from a consumer and bystander perspective.

Comparison of Smoke Yield Data Collected from Different Laboratories

Abstract In the context of increasing tobacco product regulations, more requirements are observed for the reporting of smoke constituent yield data and its variability e.g., US Food and Drug Administration (FDA). The objective of this work was to evaluate the relevance of the short term standard deviation to describe the variability of measurements using the dataset of the CORESTA 2006 Joint Experiment which included a number of cigarette smoke constituents more recently identified by FDA for reporting. Their testing protocol required the analysis of Kentucky Reference cigarettes 2R4F and 1R5F performing five replicates run over consecutive days, repeated during three different time periods. This dataset provided access to different sources of smoke yield variability across measurements: short term and medium term within-laboratory variability and among-laboratory variability. For each reference cigarette, analysis of variance on one factor (laboratory) combined with the Newman-Keuls multiple range test was performed to compare data generated across laboratories. Results showed that the expression of yield variability as an individual standard deviation (describing repeatability) gives erroneous conclusions due to the major contribution of amonglaboratory variability not being taken into account. The different sources of variability can be taken into account in the comparison using the critical difference, as described in the ISO Standard 5725 part 6. This paper shows the importance of having i) the appropriate statistical methods to compare results from different laboratories in order to avoid erroneous conclusions, and ii) validated and standardized methods with known precision across laboratories. Moreover, it was demonstrated that the number of replicates had only a minor effect on product comparison on the basis of the critical difference as a function of repeatability and reproducibility of the methods.