Non-targeted assessment in the development of smoke-free products

In addition to the quantitative analysis of 58 harmful and potentially harmful constituents (HPHCs), we also adopt a strategy for the comprehensive, non-targeted screening of smoke-free product aerosols. Quantitative analysis targets specific HPHCs of interest to the exclusion of all others, while our non-targeted approach aims to identify any chemicals which may be present in the aerosol.

Our non-targeted assessment involves the use of chromatographic separation coupled with high resolution mass spectrometry. Since the chemical diversity of constituents within an aerosol is so large, a number of overlapping methods using both gas and liquid chromatography are required to ensure comprehensive analytical coverage.

Chromatographic separation and mass spectrometry

For each method,  an array of retention index markers are included in order to improve the speed and accuracy of compound identification. In addition, a number of stable isotope-labelled internal standards are included in order to provide a semi-quantitative estimate of constituent abundance.  Compounds are identified using an automated software platform developed in-house, which interrogates both commercially available and custom built mass spectral databases and compares a number of predicted versus measured parameters, such as relative retention time, to improve the certainty for identification.

When developing smoke-free products or creating subsequent iterations of an existing smoke-free product, it is important to understand whether any new compounds are generated in comparison to a reference product or previous version. It is also important to identify whether any significant increase in the concentration of a common constituent has occurred. In this situation, non-targeted differential screening is performed, whereby data from the non-targeted screening of different products are compared. Statistical models are used to filter compounds with significant differences, followed by a ranking procedure which considers the relative differences in abundance of each compound as well as the absolute abundance. The findings are then passed on for toxicological assessment.