Ashley Sage

Modern eating habits have led to the further diversification of an already complex food supply chain. The public confidence in the food supply is not only impacted by publicized crises involving contaminations, but also through the misreporting of nutritional information. Food analysis is integral to the whole supply chain, be it through a rapid response to a food crisis, such as the fipronil egg scandal, the continued monitoring of pesticides that could harm an unsuspecting public, or accurately reporting nutritional information to provide the information the public needs to make an informed decision about the food they eat. Each event is fraught with difficulties, but by developing new methods of analysis, crises in the food industry can be avoided, or their effects mitigated. This article highlights three events that require new method development to meet various detection needs, ranging from the detection of pesticides (such as fipronil and glyphosate), to the detection and quantification of fat-soluble vitamins.

	Modern diets have resulted in unprecedented growth and diversification of the food supply chain. The necessity of a continual supply of food means crops are commonly being treated with pesticides that are essential to reduce the risk of failed harvests. These chemicals are toxic to both insects and humans, and as such the public must be protected from unsafe concentrations of pesticides. Regulations imposed by food standard agencies dictate pesticide maximum residue limits (MRLs), which ensure the food on supermarket shelves is safe for consumption. In addition to ensuring food is free from contaminants, it is also essential to provide the public with accurate nutritional information to help enable the healthy growth of the global population.

	To meet these goals, emphasis is placed on food content analysis to ensure quality and consistency between batches. Characterization and detection techniques, such as mass spectrometry (MS), offer manufacturers and producers the ability to screen large quantities of samples in a timely fashion, while guaranteeing reliable, repeatable measurements. Approaches to analysis are generally twofold-proactive monitoring of essential nutrients and possible contaminants, and crisis response, where widespread contamination requires the rapid development and deployment of analytical methods and equipment.

Rapid Response: Fipronil Egg Contamination

	One recent example highlighting the need for a crisis response is the fipronil contamination of eggs, which resulted in the recall of millions of eggs. Fipronil is an insecticide, belonging to the phenylpyrazole family of chemicals, developed in the 1980s (1). Its high toxicity makes fipronil useful for controlling levels of insects including fleas, mites, and cockroaches, and is even useful against pests resistant to various insecticides (2). However, in July 2017, fipronil made news headlines after it was found to be present in eggs across Europe. This crisis was so widespread that, by the end of August, fipronil-contaminated eggs were detected in 15 European countries and as far afield as Hong Kong and China.

	Fipronil treatment for crops used in the food chain is prohibited, and the US Environmental Protection Agency (EPA) has labeled fipronil as possibly carcinogenic, prohibiting its presence in the food chain (3). Furthermore, the European Food Safety Authority (EFSA) dictates fipronil concentrations of under 5 µg/kg to be safe for human consumption (4). Complying with concentrations dictated by regulation is therefore vital for manufacturers and producers to ensure the continued safety and confidence in food supplied to the public. Detection methods form one essential part of this process, identifying and quantifying potential contaminations prior to distribution in the food chain. There are several plausible methods of detecting contaminants such as fipronil in samples of food. The most common detection methods include liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS), with both requiring different methods of sample preparation prior to analysis.

	The challenge arises in detecting fipronil concentrations at the low level stipulated by government regulation, but novel methods capable of detecting fipronil and its associated metabolite, fipronil sulfone, have been developed. Since the fipronil contamination scandal began, demand for a fast, sensitive detection method has only continued to grow. One such detection method involves a modified Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) sample preparation technique prior to detection, using a triple quadrupole instrument and electrospray ionization (ESI). The high sensitivity of detection and ability to analyze two compounds in the same run enable regulation-compliant detection in a timely manner. This developed method can detect fipronil, as well as its major metabolite fipronil sulfone, to the MRL level of 5 µg/kg, as demonstrated in Figure 1 (5).


	Figure 1: A chromatogram showing the clear separation of analytes, identifying fipronil and amitraz (another insecticide) and their related metabolites. 1. DPMF, 2. DMA, 3. DMF, 4. fipronil, 5. fipronil sulfone, 6. amitraz.

	In responding to a food contamination crises, it is also prudent to develop methods that can screen for multiple contaminants at once, potentially preventing contamination from other, unexpected sources. Using nontargeted approaches, such as sequential window acquisition of all theoretical mass spectra (SWATH-MS) acquisition, contaminant detection is not limited to the chosen molecule, in this case enabling the analysis of fipronil and other contaminants such as pesticides and polyaromatic hydrocarbons (6). Combining instrumentation that provides linear, reproducible contaminant detection to regulation-specific concentrations, with novel sample preparation methods, is essential to avoid repeated events, and helps improve public confidence in the integrity of the food supply chain.

Continual Monitoring: Glyphosate Pesticide

	While fipronil is known to be hazardous for health, regulatory advice on other pesticides, such as glyphosate, is conflicted. Glyphosate is a widely used broad-spectrum systemic herbicide and crop desiccant. While it has recently made headlines for its potentially hazardous nature to humans as a possible carcinogen, its impact on human health is contested, and, therefore, the use of glyphosate as a farming pesticide is still permitted (7). In cases where potentially harmful pesticides are being used, continual monitoring is required to ensure chemical concentrations in foods are safe. Glyphosate is used globally and has been detected at trace levels, along with related metabolites, in 45% of European topsoils (8), and in samples of milk (9).

	The controversy surrounding the use and potential contamination of glyphosate has placed greater emphasis on data collection and analysis methods to ensure levels of glyphosate in food samples fall below the safe maximum residue level (MRL) (reported by the EFSA as 50 µg/kg) (10). However, while the analysis of glyphosate and its associated metabolites is essential, its detection presents different sample preparation and analysis challenges that must be overcome. The high polarity of glyphosate and its related metabolites previously made sample extraction and LC analysis difficult. To overcome retention issues, derivatization is employed using a method with fluorenylmethyloxycarbonyl chloride (FMOC-Cl) as the derivatization reagent to convert glyphosate into an analogue that can then be analyzed. However, while this approach enables detection, it is both complicated and time-consuming, and fails to detect pure glyphosate and its metabolites.

	Currently, the detection of underivatized glyphosate can be achieved using new methods of extraction coupled with instrumentation. One such underivatized method of detection starts by using the Quick Pesticide Preparation (QuPPe) extraction method to prepare samples (11). Using a combination of this approach with sensitive MS instruments, accurate quantification of glyphosate and its metabolites can be achieved. By combining the LC–MS/MS method with differential mobility separation (DMS) technology, interferences can be removed from analyses to improve the signal-to-noise ratio and, consequently, increase confidence in quantification results. These samples are then analyzed using LC–DMS–MS/MS to quantify and identify those contaminants present, as shown in Figure 2.


	Figure 2: MS spectra provide the ability to clearly identify and distinguish glyphosate and its metabolite AMPA and other pesticides, such as glufosinate.

	General food composition monitoring is not limited to the detection of harmful contaminants. It also forms an essential component of the accurate reporting of nutritional information for packaging labels. Vitamins are vital nutrients that are essential for an individual's growth and development. Deficiency in any vitamin is detrimental to health, and is linked to a multitude of health issues. For instance, deficiency in vitamin D leads to the bone disorder known as rickets, and has been associated with other health problems, including heart disease and cancer (12). While most vitamins can be obtained through natural means-exposure to sunlight is the best source of vitamin D-this is not always possible for some. Vitamin supplements are one option, and are commonly incorporated into food (for example, infant formula). It is therefore imperative to report accurate nutritional information on food packages to ensure an individual's vitamin needs are met, and for manufacturers to correctly advertise the benefits of their products.

	Vitamins broadly separate into two categories: water-soluble (vitamins B and C), and fat-soluble (vitamins A, D, E, and K). Detection of water-soluble vitamins is relatively easy, with analysis possible using MS. Conversely, analysis of fat-soluble vitamins is difficult, owing to the challenges associated with MS detection. These problems originate from the presence of lipids in fat-soluble vitamin samples that cause an effect known as 

 (13), negatively affecting the detection, precision, and capability of a mass spectrometer. The ease in the detection of water-soluble vitamin samples is a direct result of the absence of lipids, enabling clean detection of vitamin B and C in samples (14). No uniform solution to ion-suppression exists, but its effects can be circumvented by the removal of lipids.

	The detection of vitamins provides a specific detection challenge and, until recently, it was difficult to detect fat-soluble vitamins using LC–MS methods. Food samples contain various concentrations of vitamins, ranging from parts per billion to parts per million. To obtain clean, analyzable detection of fat-soluble vitamins, the lipid content should be removed from food samples. This reduces the ion suppression, and enables robust MS analysis within a single chromatogram that identifies multiple vitamins (see Figure 3). Combining sensitive MS methods with associated expertise in methodology allows universal application of the sample preparation and a simple analysis of vitamin concentrations in various food samples, meeting the specific requirements of the customer.


	Figure 3: A single chromatogram identifying the various vitamins that can be identified within a single mass spectrum run.

	Identification and quantification of potential contaminants and nutrients are essential to maintaining the integrity of the food supply chain. By avoiding unnecessary contamination of pesticides and providing clear labeling information, food manufacturers can be confident that food is safe for public consumption, while also delivering accurate nutritional information. Continual methodological and instrumentation development will enable more sensitive and timely detection to continue for years to come.

	(1) C.C. Tingle, J.A. Rother, C.F. Dewhurst, S. Lauer, and W.J. King, 

 (Royal Society of Chemistry, Information Services, Cambridge, United Kingdom, 3rd ed., 1991).

	(3) U.S. Environmental Protection Agency, New Pesticide Fact Sheet - Fipronil; EPA 737-F-96-005 (U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances (Office of Pesticide Programs, U.S. Government Printing Office Washington, DC, USA, 1996), pp 1–10.

	(4) European Commission Pesticide Database, 

ec.europa.eu/food/plant/pesticides/eu-pesticides-database/public/?event=pesticide.residue.selection&language=EN

	(5) Analysis of fipronil and amitraz insecticides, 

sciex.com/Documents/tech%20notes/Rapid-LC-MS-MS-Method-for-the-Analysis-of-Fipronil-and-Amitraz-Insecticides.pdf

	(6) Screening residual pesticides in fruit and vegetables, 

https://sciex.com/Documents/tech%20notes/X500R-QTOF-System-with-SWATH-Acquisition-for-Pesticide-Residue-Screening-in-Fruits-and-Vegetables.pdf

	(7) EFSA: Conclusion on the peer review of pesticide risk assessment of the active substance 

glyphosate,https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2015.4302

	(8) V. Silva, L. Montanarella, A. Jones, O. Fernández-Ugalde, H.G. Mol, C.J. Ritsema, and V. Geissen, 

	(9) N. Chamkasem, C. Morris, and T. Harmon, 

	(11) LC–MS/MS Analysis of Emerging Food Contaminants, 

https://sciex.com/Documents/tech%20notes/food_contaminants6500_QuPPe.pdf

	(12) D. Feldman, A.V. Krishnan, S. Swami, E. Giovannucci, and B.J. Feldman, 

	(14) Analysis of Vitamin B complex in infant formula samples, 

https://sciex.com/Documents/brochures/vitB_infant_formula_QTRAP6500_09340214.pdf

 is the Senior Manager, Applied Markets Development at Sciex, in Warrington, UK. 

 is the Applications Manager and Global Technical Leader, Food & Environmental at Sciex, in Darmstadt, Germany. 

 is the Global Marketing Manager, Food, Environment & Forensics at Sciex, in Warrington, UK. Direct correspondence to: 

Articles

In the human food supply, public confidence is affected by contaminants and misreporting of nutritional information. This article
highlights three events that required development of new mass spectrometry methods, including the detection of pesticides (such as fipronil and glyphosate), and the detection and quantification of fat-soluble vitamins.

Novel Methods Using Mass Spectrometry for Food Safety—From Contamination to Nutrition

In order to ensure the continued use of plastic packaging in food, the packaging used must be safe for contact with food products, and not cause contact contamination. Of rising concern is the role of non-intentionally added substances (NIAS). Therefore, this study assesses whether two commonly used plastic packaging materials, polyethylene and low-density polyethylene plus nylon, are safe for use. Their potential migrants are analyzed using data-independent acquisition and liquid chromatography coupled with high-resolution accurate mass spectrometry (HRAMS). Using automatic detection capabilities and filtering procedures, MS and tandem mass spectrometry (MS/MS) data were processed to find chemical formulae, and structures and toxicity information for the most abundant analytes in a given sample. Through this method, 26 migrating compounds, mainly cyclic oligomers, were identified. Using the toxicity rules set out by Cramer, 19 of these 26 compounds were identified as having moderate or high toxicity.


	(PHOTO CREDIT: SYDA PRODUCTIONS/STOCK.ADOBE.COM)

	Food packaging is a major market segment in the global food industry, often compared in size to that of the pharmaceutical industry (1). Over one third of all food packaging comprises materials made from plastic (1,2), which over the past several decades has extended to different plastic materials, copolymers, and additional ingredients.

	Packaging itself is essential to our modern society. As our food supply chain has grown to become more global, plastic packaging has been instrumental in ensuring that the food reaching consumers is safe to eat. Packaging helps to preserve food by protecting it from light, humidity, oxygen, foreign compounds, mechanical influences, and microbial contamination, all of which help to improve shelf life (1). Two polymers used frequently in food packaging include polypropylene and polyethylene, with the latter being used in various forms including low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), and high-density polyethylene (HDPE) (3).

	However, while food packaging protects from external contaminant introduction, there is increasing concern about the potential of chemical contamination from the plastic packaging itself. In fact, food contact migration is reported as one of the largest sources of food contamination, and is approximately 100–1000 times higher than that caused by pesticide residues (3,4). This migration can occur from multiple sources, including from contact with the internal face of the packaging, from diffusion and partition processes within multi-layered plastics, or even from adhesives.

	The potential health implications that plastic contamination poses to the consumer have resulted in the control and supervision of plastic materials in multiple countries. For instance, the European Union has imposed Regulation EU 10/2011, which has established specific rules for what plastic materials can be applied safely to food packaging, and lists specific compounds that are authorized for use in plastic formulations and manufacturing (5). But, this regulation does not take into account unintentional substances, often referred to as 

 (NIAS), meaning they frequently do not appear in lists of permitted ingredients. NIAS may be introduced through a variety of processes: a result of interaction between ingredients, degradation of material components, or from impurities within the raw material (6). As a result, the migration of non-authorized substances must not exceed a level of 0.01 mg/kg of food or simulant.

	To meet these strict criteria, highly sensitive and advanced analytical instruments and techniques are needed to test samples for the presence of NIAS. For nonvolatile chemicals in particular, liquid chromatography coupled to high-resolution accurate mass spectrometry (LC–HRAMS) has a proven history identifying nontarget compounds (7). In addition, non-targeted screening approaches assist in identifying potentially unknown contaminants compared to other acquisition methods. This technology has already been successfully applied to proteomics and metabolomics (8), as well as clinical and forensic toxicology (9).

	The present study investigates the migration of compounds from two different multilayer plastic packaging materials commonly used in fruit puree and juices. Using an LC–QTOF instrument, coupled with data-independent acquisition, non-targeted peaks were identified and concentrations were compared against those dictated by EU regulation. Following the successful identification of molecular formulae and structures, the toxicity of these structures was assessed to determine the potential harm such NIAS pose to consumers.

	Two commercially available multilayer plastic materials, used for the packaging of purees and juices from fruits and vegetables, were purchased over the internet for testing. The two multilayered materials used were: a polyethylene based material, and an LDPE plus nylon material.

	The migration test was performed according to the procedures established by EU Regulation 10/2011. The standardized test conditions, that simulate the long-term storage of food at or below room temperature, involve subjecting the material to 10 days of contact time with a contact temperature of 40 °C. Migration tests were performed using 1 dm

 surface area. This surface area was chosen as the regulation has previously established that materials can now be manufactured in such a way that the material is not releasing more than 10 mg per 1 dm

	Two simulants were used to measure the impact of material contact: simulant B, which consists of a solution of 3% acetic acid in water (w/v), and simulant C, which is a solution of 20% ethanol in water (v/v). For each material, 10 × 10 cm of plastic material was added to a 50 mL PTFE tube with 35 mL of the relevant simulant, in which carbendazim-d3 and malathion-d10 were added to the simulants as internal standards for quality control purposes. Three replicates and one control were performed. Each tube was placed in an incubator for 10 d at 40 °C. Afterwards, one aliquot of each sample was directly injected and analyzed by LC-HRAMS along with a calibration curve of ε-caprolactam.

	The liquid chromatography separation was carried out using an Exion LC (Sciex). Mobile phase A was made up from 98% water and 2% methanol, and mobile phase B was made up from 98% methanol and 2% water. Both phases contained 5 mM of ammonium formate and 0.1% formic acid. Separation was carried out using a Zorbax Eclipse Plus C8 column (Agilent) with a length, diameter and particle size of 100 mm, 2.1 mm and 1.8 µm, respectively. The column was thermostatted at 35 °C. The mobile phase gradient started from 80% of mobile phase A, which was maintained for 2 min. From 2 to 15 min, the amount of mobile phase B increased linearly to 100%, which was then maintained for 2 min. The mobile phase was then changed to 80% A, maintained for 3 min for re-equilibration, leading to a total running time of 20 min. An X500R (SCIEX) mass spectrometer equipped with Turbo V Source with a Twin Sprayer probe was used for acquisition. The data-independent acquisition tool SWATH Acquisition was used to analyze the data. A mixture containing 10 compounds with masses in the range of 132.9049–2034.6255 g/mol was used for calibration. SCIEX OS 1.3 was used for qualitative and quantitative analysis. The source parameters for the mass spectrometer are reported in Tables I–III.

	Control samples were run in similar conditions, which are left to stand for 10 days at 40 °C in the PTFE tube. Control samples were then compared with the three samples and used to filter out chemical peaks where the difference in intensity of the peaks was deemed to be negligible.

	A data-independent non-targeted acquisition mode was used to analyze the analytes. This approach segments the full scanned mass range into smaller segments for simpler MS/MS analysis, reducing the complexity of the fragmentation spectra. This allows for a retrospective analysis of the data, while ensuring that overlapping analyte peaks are not missed. This analysis proved vital in this study, owing to the complex overlap of spectra.

	Using the strategy outlined in the experimental section, a total of 3149 spectral features were identified in the polyethylene-based material. Using the filtering strategy, the number of elucidating ions decreased from 3149 to 57 (which is characteristic of polyethylene packaging material), which then further decreased to only 21 ions after focusing on the most abundant compounds (those with a signal intensity above 1 × 10

). However, to date, there is no library of NIAS substances to screen against the identified compounds, and none of the relevant ions were present in the commercial MS/MS spectral library used (SCIEX). MS/MS libraries are constantly evolving but still only cover a limited number of analytes. For those compounds whose MS and MS/MS had the lowest associated error, probable structures were constructed using ChemSpider and then modelled in silico to compare fragmentation patterns against those observed. Owing to the numerous possible structures, chemical intuition and prior knowledge of the substance was essential to rule out many database structures.


	Figure 1: Spectra of the two materials obtained using simulant C. The most abundant peaks are identified using compound ID numbers, the identities of which are reported in Table IV.

	From the two packaging materials, a total of 26 migrating compounds were identified from the screening method. Of these, 21 were assigned a plausible structure, which was later confirmed by fragmentation and bibliography agreement. A further 3 migrants were assigned a plausible structure based on fragmentation data, but these could not be confirmed. The final two structures could only be assigned molecular formulae, with not enough information collected to accurately assign structures. Spectra for the two materials using simulant C are reported in Figure 1. The summarized identity of those compounds identified is summarized in Table IV.

	Most migrants were identified in both materials. The only compound listed in Regulation EU 10/2011 was caprolactam, a monomer of nylon (compound 2). It was found that caprolactam was present at 42 mg/kg in the polyethylene material and 9.33 mg/kg in the LDPE + nylon material. As European legislation permits concentrations of only 15 mg/kg, the migrant compound caprolactam is present at more than two-fold higher concentrations in the polyethylene-based material (5). In addition, four cyclic oligomers of caprolactam were detected in both materials corresponding to the dimer, trimer, tetramer, and pentamer (compounds 4, 3, 5, and 6 respectively). This phenomenon is not surprising as oligomers up to the octamer have previously been identified in other migration studies (3, 9, 10).

	Two other substances were identified: the plasticizer bis (2-methoxyethyl) adipate (compound 9) and diethyl 5-({[(2,4,5-trimethoxybenzoyl)oxy]acetyl}amino) isophthalate (compound 15). These were the results of the best matches based on identified chemical structures and fragmentation patterns.

	All other compounds identified were classified as NIAS, with the majority being oligomers. The main migrants were oligomers from polyurethane adhesives. Cyclic ester oligomers were found to be made up of the monomers adipic acid (AA), phthalic acid (PA), diethylene glycol (DEG), monoethylene glycol (MEG) and neopentilglycol (NPG) in the combination 1:1 (AA-DEG, PA-DEG), 1:2 (PA-DEG-DEG), 2:2 (AA-MEG-AA-MEG, AA-DEG-AA-DEG, PA-DEG-PA-DEG), 1:1:2 (AA-MEG-AA-DEG, AA-DEG-PA-DEG) or 1:1:1:1 (PA-MEG-AA-DEG, PA-DEG-AA-NPG). However, once again most of the oligomers were not present in any library database consulted, and therefore identification was made based on a bibliographic search of their molecular masses. All oligomers were identified in the literature except for 3,6,9,12,15-Pentaoxabicyclo(15.3.1)henicosa-1(21),17,19-triene-2,16-dione, an ester whose appearance was attributed to the conceivable combination of monomers present in the materials.

	Only four substances were present only in the LDPE and nylon material. These are labelled as peaks 20–24 in Figure 1. Compounds 21, 22 and 24 had not been fully described in the literature, and there is currently no thorough hypothesis or explanation for the formation of these compounds in the present study. However, the peaks displayed similar characteristics to other oligomers already identified in the simulants. Peak 20 was identified as 1/6-dioxacyclodecane-7,12-dione and is attributed in the literature to the presence of polyurethane adhesives used to laminate packaging multilayer materials (11). Compound 23 was identified as 1,6,13,18-tetraoxacyclotetracosane-2,5,14,17-tetrone, also found in compostable adhesives (12).

	The two peaks that were not identified are those labelled as 17 and 19 in Figure 1. It was only possible to assign the most probable chemical formula, identified as C

. Due to the number of potential structures in the databases (22 and 83 possibilities respectively), it was not possible to identify a specific structure.

	The chromatographs for the migration of compounds for simulants B and C are overall very similar. The overlapping chromatographs are shown in Figure 2. Only two peaks were identified as exclusively present in simulant B, labelled as compounds 25 and 26. Based on individual masses, these molecules were identified as the cyclic oligomers AA-DEG and AA-DEG-PA-DEG with a molecule of water.


	Figure 2: Overlapping spectra of the two materials using simulants B and C. Compounds 20–24 are only observed in simulant B and are identified in Table IV. 

	The toxicity of individual NIAS was then assessed to determine whether those compounds identified in the analysis are hazardous to public health. A bibliographic search for their toxicity found that the majority have not been registered in EU regulation. Thus, a theoretical assessment was performed using the Threshold of Toxicological Concern (TTC) approach (13–15). TTC is based on Cramer rules, which assigns the toxicity of compounds based on the molecular structure into the following categories: low (class I), moderate (class II), and high (class III). Cramer has also devised a maximum recommended intake value for each compound class of 1.8, 0.54, and 0.09 mg/person/day, respectively. Using these rules, only 7 of the identified compounds were identified as low toxicity, with the results for all compounds summarized in Table IV.

	Due to the potential toxicity these compounds pose, their presence in plastic materials intended for food could generate a risk for consumers. Given the peak intensity, and the high presence of caprolactam, the polyethylene-based material could pose a higher risk to consumers compared to the LDPE material.

	This study sought to identify the potential migrating substances from food packaging contact. Two packaging materials were tested, polyethylene and low-density polyethylene plus nylon. A total of 26 substances were identified in this study, combining those identified in the LDPE and polyethylene materials: 21 have been assigned a confirmed structure, three have a tentative assigned structure and the final two only have assigned molecular formulae. The majority of the compounds are considered by Cramer's rules to be of moderate or high toxicity meaning their presence should be restricted to low concentrations. Only one compound identified is listed in the Regulation (EU) 10/2011: caprolactam, which was found to be above suggested concentrations in the sample of polyethylene tested. This work has shown the relevance and importance of evaluating NIAS in food contact materials to ensure consumer and food safety.

https://doi.org/10.1016/j.scitotenv.2009.05.006

	(2) B. Athenstädt, M. Fünfrocken, and T.C. Schmidt, 

	(3) M. Hoppe, P. de Voogt, and R. Franz, 

https://doi.org/10.1016/j.tifs.2016.01.018

https://doi.org/10.1016/j.foodcont.2014.05.044

	(5) Commission Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food, European Commission, The Official Journal of the European Union, 2011, 15.1.2011. 

https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32011R0010&from=EN

	(6) C. Bignardi, A. Cavazza, C. Laganà, P. Salvadeo, and C. Corradini, 

https://doi.org/10.1016/j.foodcont.2016.07.013

	(7) A.E. Lewandowska K. Macur, P. Czaplewska, J. Liss, K. Lukaszuk, and S. Oldziej, 

https://doi.org/10.1021/acs.jproteome.7b00366

	(8) M.P. Elmiger, M. Poetzsch, A.E. Steuer, and T. Kraemer, 

https://doi.org/10.1007/s00216-017-0594-1

	(9) D. Jenke, M. Poss, S. Sadain, J. Story, W. Smith, and D. Reiber, 

	(10) S. Úbeda, M. Aznar, P. Vera, C. Nerín, L. Henríquez, L. Taborda, and C. Restrepo, 

https://doi.org/10.1080/19440049.2017.1346390

	(11) J.S. Félix, F. Isella, O. Bosetti, and C. Nerín, 

https://doi.org/10.1007/s00216-012-5965-z

	(12) E. Canellas, P. Vera , and C. Nerín, 

https://doi.org/10.1007/s00216-015-8848-2

	(13) G.M. Cramer, R.A. Ford, and R.L. Hall, 

https://doi.org/10.1016/S0015-6264(76)80522-6

	(14) I.C. Munro, A.G. Renwick, and B. Danielewska-Nikiel, 

https://doi.org/10.1016/j.toxlet.2008.05.006

	(15) C. Nerin, P. Alfaro, M. Aznar, and C. Domeño, 

https://doi.org/10.1016/j.aca.2013.02.028

is the Senior Manager of Applied Markets Development at Sciex, in Warrington, UK. 

is the Applications Manager and Global Technical Leader for Food & Environmental at Sciex, in Darmstadt, Germany. 

 is a Professor of Analytical Chemistry at the University of Almeria, Spain. 

 is a postdoctoral researcher at the University of Almeria, Spain. 

 is a postdoctoral researcher at the University of Almeria, Spain. Direct correspondence to: 

This study assesses whether two commonly used plastic packaging materials are safe for use. Their potential migrants are analyzed using data-independent acquisition and liquid chromatography coupled with high-resolution, accurate-mass mass spectrometry.

Ashley Sage

Articles

Novel Methods Using Mass Spectrometry for Food Safety—From Contamination to Nutrition

Comprehensive Identification of Migrating Compounds from Plastic Food Packaging Materials Using High-Resolution Mass Spectrometry