Formatted Title
Non-Targeted Analysis and High Resolution Mass Spectrometry: The Basic and Beyond
Background/Objectives
Continuing advances in high-resolution mass spectrometry (HRMS) have led to massive developments in the analysis of contaminants of emerging concern using non-targeted analysis. Non-targeted analysis or non-target screening is a general term for any analysis of an analyte without previous knowledge of the site or analytical reference standard. These methods are usually in non-standard format, are program or research based, and are used in screening applications. Non-targeted analysis for PFAS includes methods like: total oxidizable precursor (TOP) assay, adsorbable organic fluorine (AOF), and HRMS analysis. HRMS analysis provides the most detailed characterization of analytes at the site, however it is data and time intensive, qualitative, or semi-quantitative for analytes without standards, and results may be difficult to interpret.
Approach/Activities
Non-targeted analysis by HRMS answers the question “What is in my sample?” Sample preparation is limited to not bias the results and once data are collected, they can be interpreted many different ways. HRMS (e.g., Orbitrap and QTOF) provide high mass accuracy (<5 ppm or 0.001 Dalton), mass-resolving power > 30,000 R (full width at half maximum), high scan speeds, and large dynamic range (ppt -ppb). When HRMS is coupled with a separation technique, such as liquid chromatography or gas chromatography, HRMS can be used to identify, detect, and annotate non-targeted analytes in complex matrices for forensics, water quality monitoring, food safety, environmental toxicology, and human exposure for exogenous or endogenous compounds.
Data interpretation can be quantitative, semiquantitative, or qualitative. (1) A calibration curve with target analytes can be analyzed alongside the samples and quantitation is performed on a HRMS system using the parent mass as the quantitative ion. (2) Any number of user-defined suspect lists can be created and screened against the data. When available, spectral libraries can be used to add confidence in an identification, however, the user must be aware of the quality of the spectral library as user generated libraries may be unreliable. (3) Finally, a true non-targeted approach may be used in exploratory cases in which no prior knowledge is known about the site.
Results/Lessons Learned
Data interpretation is the crux of non-targeted analysis. Confidence intervals are used to explain to quality and degree of evidence in an identification. New tools are being published which aid in the data interpretation. Best Practices for Non Targeted Analysis (BP4NTA) has created a Study Reporting Tool to demystify the data collection, quality control metrics, data processing, and data outputs. NIST and NORMAN are publishing resources for public use such as suspect lists, open-source spectral libraries, and data interpretation tools. For those who need more details from the TOP Assay or TOF results, non-targeted analysis may be the next tool for more specific characterization of a site.