Application of Ion Mobility Spectrometry and the Derived Collision Cross Section in the Analysis of Environmental Organic Micropollutants.

Ion mobility spectrometry (IMS) is a rapid gas-phase separation technique, which can distinguish ions on the basis of their size, shape, and charge. The IMS-derived collision cross section (CCS) can serve as additional identification evidence for the screening of environmental organic micropollutants (OMPs). In this work, we summarize the published experimental CCS values of environmental OMPs, introduce the current CCS prediction tools, summarize the use of IMS and CCS in the analysis of environmental OMPs, and finally discussed the benefits of IMS and CCS in environmental analysis. An up-to-date CCS compendium for environmental contaminants was produced by combining CCS databases and data sets of particular types of environmental OMPs, including pesticides, drugs, mycotoxins, steroids, plastic additives, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), as well as their well-known transformation products. A total of 9407 experimental CCS values from 4170 OMPs were retrieved from 23 publications, which contain both drift tube CCS in nitrogen (DTCCSN2) and traveling wave CCS in nitrogen (TWCCSN2). A selection of publicly accessible and in-house CCS prediction tools were also investigated; the chemical space covered by the training set and the quality of CCS measurements seem to be vital factors affecting the CCS prediction accuracy. Then, the applications of IMS and the derived CCS in the screening of various OMPs were summarized, and the benefits of IMS and CCS, including increased peak capacity, the elimination of interfering ions, the separation of isomers, and the reduction of false positives and false negatives, were discussed in detail. With the improvement of the resolving power of IMS and enhancements of experimental CCS databases, the practicability of IMS in the analysis of environmental OMPs will continue to improve.

Migration of contaminants from printed masks for children to saliva simulant using liquid chromatography coupled to ion mobility-time of flight-mass spectrometry and gas chromatography-mass spectrometry.

The COVID-19 pandemic has led to children using polymeric FFP2 and polymeric surgical masks on a daily basis. Children often bite and suck on such masks as they wear them closed to their mouths. In this work, the migration of contaminants from printed and unprinted children`s masks to a saliva simulant has been studied. Liquid chromatography coupled to ion-mobility quadrupole time-of-flight mass spectrometry has been used for the detection and identification of non-volatile migrants. An orthogonal projection to latent structures - discriminant analysis (OPLS-DA) was applied to compare the data from the printed masks against the data from the unprinted ones. Headspace solid phase microextraction coupled to gas chromatography mass spectrometry was used to assess the migration of volatile compounds. Thirteen compounds were found in the masks with concentrations ranging from 5 ng/g to 254 ng/g. Toluene, chlorobenzene, irganox 1076 and 2-(2-butoxyethoxy)ethyl acetate were all found to migrate from the masks studied. Moreover, differences between the migrants from printed and unprinted FFP2 masks were found. Octocrylene, 4-(dimethylamine)benzoate, methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and tris(3-methylphenyl)phosphate were found to migrate only from printed masks. Toluene that migrated from all the masks studied and tris(3-methylphenyl)phosphate, that migrated only from printed masks, have been listed as hazardous priority substances.

Prediction of Collision Cross-Section Values for Extractables and Leachables from Plastic Products.

The use of ion mobility separation (IMS) in conjunction with high-resolution mass spectrometry has proved to be a reliable and useful technique for the characterization of small molecules from plastic products. Collision cross-section (CCS) values derived from IMS can be used as a structural descriptor to aid compound identification. One limitation of the application of IMS to the identification of chemicals from plastics is the lack of published empirical CCS values. As such, machine learning techniques can provide an alternative approach by generating predicted CCS values. Herein, experimental CCS values for over a thousand chemicals associated with plastics were collected from the literature and used to develop an accurate CCS prediction model for extractables and leachables from plastic products. The effect of different molecular descriptors and machine learning algorithms on the model performance were assessed. A support vector machine (SVM) model, based on Chemistry Development Kit (CDK) descriptors, provided the most accurate prediction with 93.3% of CCS values for [M + H]+ adducts and 95.0% of CCS values for [M + Na]+ adducts in testing sets predicted with <5% error. Median relative errors for the CCS values of the [M + H]+ and [M + Na]+ adducts were 1.42 and 1.76%, respectively. Subsequently, CCS values for the compounds in the Chemicals associated with Plastic Packaging Database and the Food Contact Chemicals Database were predicted using the SVM model developed herein. These values were integrated in our structural elucidation workflow and applied to the identification of plastic-related chemicals in river water. False positives were reduced, and the identification confidence level was improved by the incorporation of predicted CCS values in the suspect screening workflow.

Ion-Mobility Quadrupole Time-of-Flight Mass Spectrometry: A Novel Technique Applied to Migration of Nonintentionally Added Substances from Polyethylene Films Intended for Use as Food Packaging.

Nontarget analysis of nonvolatile substances in complex samples is a very challenging task that requires powerful analytical techniques and experience of analyzing such samples. An extensive study was conducted in order to identify nonintentionally added substances (NIAS) migrating from 18 polyethylene (PE) samples intended to be in contact with food. The migration assays were performed in five simulants and analyzed by ultrahigh-performance liquid chromatography (UPLC) coupled to an ion-mobility separation (IMS) quadrupole-time-of-flight (QTOF) mass spectrometer. This experimental setup provides a novel and powerful tool for this type of nonvolatile and nontargeted analysis. Thirty-five compounds were identified, 17 of which were NIAS. Methyl and ethyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate were found to be degradation products of either Irganox 1010 or Irganox 1076. Additionally, breakdown products including hexa-heptadecanamide, N,N'-1,2-ethanediylbis- and 11-eicosenamide were identified together with impurity reaction products, e.g., dibutyl amine or compounds of unknown origin like phosphine oxide, tributyl-. Forty-five percent of the detected compounds are in the positive list contained in Regulation 10/2011/EU, and their migration values were below their specific migration limits. The risk assessment for the rest of the compounds was carried out by comparing their migration values to the maximum concentration recommended by Cramer, e.g., ethyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate and benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 1,1'-[2,2-bis(hydroxymethyl)-1,3-propanediyl] ester (both class II toxicity), heptadecanamide, N,N'-1,2-ethanediylbis-, and phosphine oxide, tributyl- (both class III toxicity) were above the maximum concentration values for three samples that were migrated to ethanol 95%, and therefore, these samples are not suitable for food contact. The analytical tools and procedures used in this study are presented and discussed in detail.

Nano selenium as antioxidant agent in a multilayer food packaging material.

Selenium nanoparticles (SeNPs) were incorporated in a flexible multilayer plastic material using a water-base adhesive as vehicle for SeNPs. The antioxidant performance of the original solutions containing spherical SeNPs of 50-60 nm diameter, the adhesive containing these SeNPs, and the final multilayer plastic material to be used as food packaging were quantitatively measured. The radical scavenging capacity due to SeNPs was quantified by a free radical assay developed in the laboratory and by the diphenyl-1-picrylhydrazyl (DPPH) method. DPPH was not efficient to measure the scavenging capacity in the multilayer when the free radical scavenger is not in the surface in contact with it. Several multilayer laminated structures composed by [PET (20 m)-adhesive-LDPE (with variable thickness from 35 to 90 µm)] were prepared and measured, demonstrating for the first time that free radicals derived from oxygen (OH·, O2·, and O2H) cross the PE layer and arrive at the adhesive. SeNPs remain as such after manufacture and the final laminate is stable after 3 months of storage. The antioxidant multilayer is a non-migrating efficient free radical scavenger, able to protect the packaged product versus oxidation and extending the shelf life without being in direct contact with the product. Migration tests of both Se and SeNPs to simulants and hazelnuts demonstrated the non-migrating performance of this new active packaging. Graphical abstract ᅟ.

UPLC-ESI-Q-TOF-MS(E) and GC-MS identification and quantification of non-intentionally added substances coming from biodegradable food packaging.

Biodegradable packagings are made by combination of several materials creating a multilayer with the properties needed. Each material, including the adhesive, could contain substances that could migrate to the food. In this work, gas chromatography coupled with mass spectrometry and ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used to identify the biodegradable adhesive compounds. Five of the 13 compounds identified were nonintentionally added substances; they were neoformed compounds created by the reaction of added compounds in the adhesive. Moreover, the migration of the compounds through four different biodegradable materials-paper, polylactic acid, ecovio®, and polyvinyl alcohol-was studied for the first time. Three of the 13 compounds identified in the adhesive migrated from the adhesive to Tenax®, which was used as a solid food simulant. One of them, 2,4,7,9-tetramethyl-5-decyne-4,7-diol, was an intentionally added substance, and the other two were 1,6-dioxacyclododecane-7,12-dione and 1,6,13,18-tetraoxacyclotetracosane-7,12,19,24-tetraone, which were nonintentionally added substances identified in this work. Higher migration values (ranging from 0.81 to 2.07 mg/kg) were observed for migration through ecovio® than through the multilayer made by combination of ecovio® and polyvinyl alcohol (0.07-0.39 mg/kg) owing to the barrier effect provided by polyvinyl alcohol. The migration values for migration through paper and polylactic acid were below the limits of detection.

Three-phase hollow-fiber liquid-phase microextraction combined with HPLC-UV for the determination of isothiazolinone biocides in adhesives used for food packaging materials.

The present study deals with the development of a liquid microextraction procedure for enhancing the sensitivity of the determination of 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one in adhesives. The procedure involves a three-phase hollow-fiber liquid-phase microextraction using a semipermeable polypropylene membrane, which contained 1-octanol as the organic phase in the pores of the membrane. The donor and acceptor phases are aqueous acidic and alkaline media, respectively, and the final liquid phase (acceptor) is analyzed by HPLC coupled with diode array detection. The most appropriate conditions were extraction time 20 min, stirring speed 1400 rpm, extraction temperature 50°C. The quantification limits of the method were 0.123 and 0.490 µg/g for 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one, respectively. Three different adhesive samples were successfully analyzed. The procedure was compared to direct analysis using ultra high pressure liquid chromatography coupled with TOF-MS, where the identification of the compounds and the quantification values were confirmed.

Identification of non-volatile compounds and their migration from hot melt adhesives used in food packaging materials characterized by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The identification of unknown non-volatile migrant compounds from adhesives used in food contact materials is a very challenging task because of the number of possible compounds involved, given that adhesives are complex mixtures of chemicals. The use of ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-MS/QTOF) is shown to be a successful tool for identifying non-targeted migrant compounds from two hot melt adhesives used in food packaging laminates. Out of the seven migrants identified and quantified, five were amides and one was a compound classified in Class II of the Cramer toxicity. None of the migration values exceeded the recommended Cramer exposure values.

Identification of Nonvolatile Migrates from Food Contact Materials Using Ion Mobility-High-Resolution Mass Spectrometry and in Silico Prediction Tools.

The identification of migrates from food contact materials (FCMs) is challenging due to the complex matrices and limited availability of commercial standards. The use of machine-learning-based prediction tools can help in the identification of such compounds. This study presents a workflow to identify nonvolatile migrates from FCMs based on liquid chromatography-ion mobility-high-resolution mass spectrometry together with in silico retention time (RT) and collision cross section (CCS) prediction tools. The applicability of this workflow was evaluated by screening the chemicals that migrated from polyamide (PA) spatulas. The number of candidate compounds was reduced by approximately 75% and 29% on applying RT and CCS prediction filters, respectively. A total of 95 compounds were identified in the PA spatulas of which 54 compounds were confirmed using reference standards. The development of a database containing predicted RT and CCS values of compounds related to FCMs can aid in the identification of chemicals in FCMs.

Prediction of Collision Cross Section Values: Application to Non-Intentionally Added Substance Identification in Food Contact Materials.

The synthetic chemicals in food contact materials can migrate into food and endanger human health. In this study, the traveling wave collision cross section in nitrogen values of more than 400 chemicals in food contact materials were experimentally derived by traveling wave ion mobility spectrometry. A support vector machine-based collision cross section (CCS) prediction model was developed based on CCS values of food contact chemicals and a series of molecular descriptors. More than 92% of protonated and 81% of sodiated adducts showed a relative deviation below 5%. Median relative errors for protonated and sodiated molecules were 1.50 and 1.82%, respectively. The model was then applied to the structural annotation of oligomers migrating from polyamide adhesives. The identification confidence of 11 oligomers was improved by the direct comparison of the experimental data with the predicted CCS values. Finally, the challenges and opportunities of current machine-learning models on CCS prediction were also discussed.

A Collision Cross Section Database for Extractables and Leachables from Food Contact Materials.

The chemicals in food contact materials (FCMs) can migrate into food and endanger human health. In this study, we developed a database of traveling wave collision cross section in nitrogen (TWCCSN2) values for extractables and leachables from FCMs. The database contains a total of 1038 TWCCSN2 values from 675 standards including those commonly used additives and nonintentionally added substances in FCMs. The TWCCSN2 values in the database were compared to previously published values, and 85.7, 87.7, and 64.9% [M + H]+, [M + Na]+, and [M - H]- adducts showed deviations <2%, with the presence of protomers, post-ion mobility spectrometry dissociation of noncovalent clusters and inconsistent calibration are possible sources of CCS deviations. Our experimental TWCCSN2 values were also compared to CCS values from three prediction tools. Of the three, CCSondemand gave the most accurate predictions. The TWCCSN2 database developed will aid the identification and differentiation of chemicals from FCMs in targeted and untargeted analysis.

The migration of NIAS from ethylene-vinyl acetate corks and their identification using gas chromatography mass spectrometry and liquid chromatography ion mobility quadrupole time-of-flight mass spectrometry.

An exhaustive migration study of eight corks, made of ethylene-vinyl acetate, was carried out to identify any non-volatile and volatile compounds using an untargeted approach. The challenge associated with the structural elucidation of unknowns was undertaken using both ultra-high-performance liquid chromatography coupled to an ion-mobility separation quadrupole-time of flight mass spectrometer and gas chromatography mass spectrometry. A total of fifty compounds were observed to migrate from the corks, and among these additives such as antioxidants (Butyl 4-hydroxybenzoate, Irganox 1010, Irganox 1075, Irgafos 168 and BHT) or lubricants (EBO and octadecanamide, N,N'-1,2-ethanediylbis-) were identified. A high proportion (84%) of the detected compounds was non-intentionally added substances (NIAS), and included several cyclic oligomers with different chain sequences. NIAS, such as 2,6-bis(1,1-dimethylethyl)-4-ethyl and 7,9-ditert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione, break-down products, including hexa-, hepta- and nonadecanamide, N,N'-1,2-ethanediylbis-, and oxidation products were also identified. One cork was found to be unsuitable for use as a food contact material.

The detection and elucidation of oligomers migrating from biodegradable multilayer teacups using liquid chromatography coupled to ion mobility time-of-flight mass spectrometry and gas chromatography-mass spectrometry.

Biodegradable materials are increasingly being used in manufacturing processes due to their environmental benefits. In this work, a study has been performed to assess the migration of compounds from biodegradable multilayer teacups to a tea solution. Liquid chromatography in conjunction with ion-mobility quadrupole time-of-flight mass spectrometry has been used for the elucidation of non-volatile compounds. An orthogonal projection to latent structures-discriminant analysis has been carried out to compare the tea after migration against untreated tea used as blank. Headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry has been optimised to analyse the migration of volatile compounds. Eight migrants were identified in the tea, six of which were non-intentionally added oligomers. The degree of migration for hot tea ranged from 0.05 and 4.68 mg/kg, exceeding the specific migration limit. Nevertheless, the migration to cold tea was an order of magnitude lower (between 0.003 and 0.56 mg/kg).

Screening of volatile decay markers of minced pork by headspace-solid phase microextraction-gas chromatography-mass spectrometry and chemometrics.

Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to analyze the volatile compounds of minced pork meat during storage. The origin of aromatic hydrocarbons in pork was verified by migration test. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to characterize the profile of volatile compounds in pork meat and identify the potential volatile markers associated with the spoilage of pork. A total of 41 compounds were identified. Migration test showed that the aromatic hydrocarbons in raw pork are from packaging. Three compounds: ethanol, 2,3-butanediol and 2-ethyl-1-hexanol were selected based on the loading plot and their variables importance in the projection (VIP) values, since they contribute mainly to the discrimination of pork with different storage times. These compounds can be used as additional indicators for quality control of pork.

The application of ion mobility time of flight mass spectrometry to elucidate neo-formed compounds derived from polyurethane adhesives used in champagne cork stoppers.

Polyurethane adhesives are used to bond agglomerated cork and natural disk cork to produce cork stoppers that are used in champagne bottles. These adhesives are manufactured by reacting polyols with an excess of diisocyanates. Isocyanates are highly reactive compounds that have a propensity to form non-intentionally added substances (NIAS) in the end product. In this work, ion mobility-time of flight-mass spectrometry was used to elucidate such NIAS, through the comparison of accurate mass spectra with the fragmentation patterns of proposed candidates. Twelve neo-formed compounds, including amines, amides and urethanes, resulting from the reaction of isocyanates with acetic acid and ethanol used as food simulants, were identified. Additionally, markers from champagne vs. champagne after its exposure to the adhesive were investigated using the supervised multivariate analysis method of Orthogonal Projection to Latent Structures - Discriminant Analysis. Four neo-formed compounds, resulting from the reaction of diisocyanates with malic acid or tartaric acid contained in the champagne, were identified for the first time in this work. All of the compounds identified were subsequently quantified using ultra-high pressure liquid chromatography coupled to a triple quadrupole mass spectrometer. Limits of detection were below 5 µg/kg in the food simulants and below 30 µg/kg in champagne samples. Migration levels ranged from 70 to 721 µg/kg, with most of them exceeding the specific migration limit established for Cramer class III compound (90 µg/kg).

Discovery and Characterization of Phenolic Compounds in Bearberry (Arctostaphylos uva-ursi) Leaves Using Liquid Chromatography-Ion Mobility-High-Resolution Mass Spectrometry.

The characterization and quantification of phenolic compounds in bearberry leaves were performed using hyphenated ion mobility spectroscopy (IMS) and a quadrupole time-of-flight mass spectrometer. A higher identification confidence level was obtained by comparing the measured collision cross section (TWCCSN2) with predicted values using a machine learning algorithm. A total of 88 compounds were identified, including 14 arbutin derivatives, 33 hydrolyzable tannins, 6 flavanols, 26 flavonols, 9 saccharide derivatives, and glycosidic compounds. Those most reliably reproduced in all samples were quantified against respective standards. Arbutin (47-107 mg/g), 1,2,3,4,6-pentagalloylglucose (6.6-12.9 mg/g), and quercetin 3-galactoside/quercetin 3-glucoside (2.7-5.7 mg/g) were the most abundant phenolic components in the leaves. Quinic acid and ellagic acid were also detected at relatively high concentrations. The antioxidant activity of the most abundant compounds was evaluated. A critical view of the advantages and limitations of traveling wave IMS and CCS for the discovery of natural products is given.

The use of ion mobility time-of-flight mass spectrometry to assess the migration of polyamide 6 and polyamide 66 oligomers from kitchenware utensils to food.

Oligomers, are, in general, unknown components of the polymer. These oligomers can migrate from the polymer into the food and become a non-intentionally added substance to the food. In this work, ion mobility time-of-flight mass spectrometry has been used to identify oligomers migrating from kitchenware. The structure elucidation of oligomers from polyamide 6 and polyamide 66 was achieved through the analysis of accurate m/z values of adducts and collision cross section values of precursor ions together with high-energy fragmentation patterns. Additionally, a method to extract oligomers from sunflower oil, cooked beans, soup and whole milk has been developed. Extraction recoveries ranged from 87 to 102% and limits of detection were from 0.03 to 0.11 mg/kg. It was observed that the migration from kitchenware to real food was below the specified migration limit of 5 mg/kg. However, this limit was exceeded for food simulants, which therefore overestimated the oligomer migration.

Compounds responsible for off-odors in several samples composed by polypropylene, polyethylene, paper and cardboard used as food packaging materials.

Seven commercial samples, consisted of plastic bags, tetrabrik and box, were evaluated by gas chromatography-olfactometry-mass spectrometry (GC-O-MS) to find the compounds responsible for off-odors in different PP, PE, multilayer cardboard and paper materials used for food contact. Migration assays were carried out with Tenax as food simulant to analyze the food safety as well as to evaluate the odor intensity after migration assay. Forty six compounds with characteristic odors were directly found in the materials studied. The strongest odors identified were acetic, propanoic and butyric with vinegar and rancid odors and octanal, nonanal and decanal with fat/soup odors, all of them found in PP and PE samples. Trimethylbenzenes with solvent and oily odors as well as terpenes with weakly woody odors were found in cardboard and paper materials. After migration, all compounds were below the European Legislation limits and maximum migration values recommended by Cramer. However propanoic, acetic and butyric acid as well as aldehydes compounds, phenol and 1-octanol were detected by sniffers, after migration assay, with high modified frequency (between 50 and 78%), what could change the organoleptic properties of packaged food.

Predicting the antioxidant capacity and total phenolic content of bearberry leaves by data fusion of UV-Vis spectroscopy and UHPLC/Q-TOF-MS.

The total phenolic content (TPC) and antioxidant capacity have been considered as important quality parameters for plant extracts. In this study, bearberry leaves were regarded as studied subject and a reliable method was established to predict the TPC and antioxidant capacity of bearberry leaves. Ultraviolet-visible spectrometry (UV-Vis) and ultra high pressure liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) were used to provide spectral fingerprinting and metabolomic profiling. The data obtained (separately and merged) were used to build partial least squares (PLS) regression model. The PLS model built by using ultraviolet-visible spectra provided a satisfactory prediction result. Mid-level data fusion using the scores significantly improved the performance of PLS regression model, the residual predictive deviations (RPDs) for TPC and α, α-diphenyl-ß-picrylhydrazyl (DPPH) were 6.258 and 6.699, respectively, showing an excellent predictive ability. This study proved the potential of combination of UV-Vis spectrometry and UHPLC/Q-TOF-MS in the prediction of TPC and antioxidant capacity of plant extracts.

Ion mobility quadrupole time-of-flight high resolution mass spectrometry coupled to ultra-high pressure liquid chromatography for identification of non-intentionally added substances migrating from food cans.

Sealants, incorporated in the lids of food cans to ensure the can is hermetically sealed, are formulated from a wide variety of compounds. These compounds and associated non-intentionally added substances (NIAS) could migrate to the food contained in the can. In this work, ion mobility quadrupole time-of-flight mass spectrometry coupled to ultra-high performance liquid chromatography (UHPLC-IM-QTOF-MS) has been used to obtain ion mobility filtered extracted ion chromatograms. Subsequently, accurate mass precursor ions and their fragments have been used to identify the compounds migrating from the sealant to the content of the cans. Moreover, the correlation between the collision cross-section (CCS) values and m/z of the compounds was used to increase the level of confidence of the identification. Seven compounds were found to have migrated to the food simulants. The compounds bis(2-hydroxy-3-tert-butyl-5-methylphenyl)dicyclopentane,1-tetradecanesulfonic acid, 1-pentadecanesulfonic acid, 1-hexadecanesulfonic acid and naphthalene-2-sulfonic acid (whose migration was over the specific migration limit established by the European Regulation 10/2011/EU) were identified as NIAS in the food simulants studied.