Optimized hidden target screening for very polar molecules in surface waters including a compound database inquiry

Abstract

Highly polar trace organic compounds, which are persistent, mobile, and toxic (PMT) or are very persistent and very mobile (vPvM) in the aquatic environment, may pose a risk to surface water, ground water, and drinking water supplies. Despite the advances in liquid chromatography-mass spectrometry, there often exists an analytical blind spot when it comes to very polar chemicals. This study seeks to make a broad polarity range analytically accessible by means of serially coupling reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) to high-resolution mass spectrometry (HRMS). Moreover, a workflow is presented using optimized data processing of nontarget screening (NTS) data and subsequently generating candidate lists for the identification of very polar molecules via an open-access NTS platform and implemented compound database. First, key input parameters and filters of the so-called feature extraction algorithms were identified, and numerical performance indicators were defined to systematically optimize the data processing method. Second, all features from the very polar HILIC elution window were uploaded to the STOFF-IDENT database as part of the FOR-IDENT open-access NTS platform, which contains additional physicochemical information, and the features matched with potential compounds by their accurate mass. The hit list was filtered for compounds with a negative log D value, indicating that they were (very) polar. For instance, 46 features were assigned to 64 candidate compounds originating from a set of 33 samples from the Isar river in Germany. Three PMT candidates (e.g., guanylurea, melamine, and 1,3-dimethylimidazolidin-2-one) were illustratively validated using the respective reference standards. In conclusion, these findings demonstrate that polarity-extended chromatography reproducibly retards and separates (very) polar compounds from surface waters. These findings further indicate that a transparent and robust data processing workflow for nontarget screening data is available for addressing new (very) polar substances in the aqueous environment.

Getting in control of persistent, mobile and toxic (PMT) and very persistent and very mobile (vPvM) substances to protect water resources: strategies from diverse perspectives

“…With such HRMS/MS systems non-targeted screening (NTS) analysis of 'unknown' PMT/vPvM molecules can be conducted. There are several openly accessible platforms such as XCMS [43], MZmine [44], FOR-IDENT [45] and patRoon [46], which cover parts of or the entire NTS data evaluation and prioritization [48] adapted with polarity extended chromatography [49] process. Using polarity extended chromatography, HRMS, FOR-IDENT and compound databases, several vPvM substances (in the log D ow range from − 9 to + 9) such as N,N′-ethylenedi(diacetamide) [12] or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-ethanol [47] could be identified in surface waters and other aqueous samples [12,40,[42][43][44].…”

Achiral SFC separations: Gold standard for the next generation of nontarget screening

“…In RPLC and HILIC there is a good correlation of retention time and hydrophobicity (or polarity). In the serial LC coupling, the retention time of molecules can be used to estimate the polarity of unknown compounds and thus to support their identification 10 . Unfortunately, there is currently no such estimation available based on retention time in SFC so far.…”

Spotlight on mass spectrometric non‐target screening analysis: Advanced data processing methods recently communicated for extracting, prioritizing and quantifying features

“…Chromatographic parameters such as RT can be connected to the physicochemical properties of an analyte. Our group demonstrated the benefits of this relationship by filtering for polar compound candidates 51,52 . NTS measurements were carried out on a chromatographic setup comprising reversed‐phase LC (RPLC) coupled in series to hydrophilic interaction liquid chromatography (HILIC) for the separation of analytes of an extended polarity range 53 .…”

“…Our group demonstrated the benefits of this relationship by filtering for polar compound candidates. 51,52 NTS measurements were carried out on a chromatographic setup comprising reversed-phase LC (RPLC) coupled in series to hydrophilic interaction liquid chromatography (HILIC)…”