Overview of legislation, methods and examples of the use of mass spectrometry to test food and beverage products for migrants from food packaging.

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Food Contact Materials: Migration testing

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 Food manufacturing equipment
– Belts, gaskets, lubricants, etc.
 Food packaging
– Paper, plastic, cartonboard, glass, etc.
 Food preparation wares
– Crockery and utensils (e.g. chopping boards, whisks)
– Gloves, apron, etc.
 Dining wares
– Cutlery
– Bowl, plate, etc.
Food Contact Materials/ Substances

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 Migration involves the mass transfer from an external source into
food by sub microscopic processes impacting food safety and quality
 Migration can occur by
1. Diffusion
– Classified as direct contact migration as it’s physicochemical dependant
– Packaging components penetrate and diffuse across packaging material
layers due to chemical interactions
2. Gas phase
– Indirect contact migration where molecules travel through gas phase
– Volatile components can migrate or “jump” from material into foods
3. Set off
– Migration due to set off of components during manufacture or storage
Migration

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 Isopropylthioxanthone (ITX)
– 2005: Ink curing agent detected in cardboard packaged milk
 Epoxydised soy bean oil (ESBO)
– 2005: Swiss survey of jarred foods identified concentrations
exceeding the TDI allowance
 Diethylhexyl phthalate (DEHP)
– 2011: Clouding agent in probiotics substituted by probable
carcinogenic compound in order to cut costs
 Primary aromatic amines (PAAs)
– 2007: Poorly manufactured polyamide utensils leach carcinogenic
amines
 Bisphenol A (BPA)
– Recent concern involving infant feeding bottles
International Migration Alerts

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International Regulations
 European Union
– Framework: 1935/2004/EC
 United States
– Code of Federal Regulation Chapter 21
– Component specific approach
 Japan
– Framework based on Food Sanitation Act, 1947
 China
– Food Safety Law, 2009
 South America
– MERCOSUR Resolution GMC 3/92
 Australasia (New Zealand and Australia)
– Limited regulations in place; refer to EU and FDA for regulatory guidance

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 Migration modelling software
– Diffusion theory and partitioning effects
– Free and commercial softwares available
– Models provide overestimation of migration
 Migration into food simulants
– Mimic food types
– Foreseeable worst case scenario
– Minimise matrix effects
 Migration into foods
– Migration under real conditions
– Various sample cleanup required
Migration Testing

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 Complex formulation of materials
– Food packaging: monolayer/ multilayer
– Use of recycled materials
 Consider food type to be packaged in final product or intended
purpose
 Set- off migration
– Incomplete curing resulting in transfer into foods
– ITX case
 Non intentionally added substances
– Impurities within raw materials
– Polymer, additive degradation or reaction products
– Contaminants
Challenges associated with FCMs

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 “Materials and articles, including active and intelligent materials and
articles, shall be manufactured in compliance with good
manufacturing practice so that, under normal or foreseeable
conditions of use, they do not transfer their constituents to food in
quantities which could:
(a) endanger human health;
(b) bring about an unacceptable change in the composition of the food;
(c) bring about a deterioration in the organoleptic characteristics thereof.”
Directive 1935/2004/EC
 All materials and articles intended to come in contact with food
should be manufactured in accordance with good practices
Foundation of FCM legislation

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 Amount of a specified component that migrates from the food contact
material or article to the food during contact permitted by regulations:
Specific Migration Limit (SML)
 Regulations and testing ensures safety limit based on toxicological
data and risk of exposure
 Regulated limits set on permitted migrates
– For example Pb from ceramics; BADGE from can coatings
– Positive list associated in EU (for plastics) and China
Specific Migration

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 Challenges associated with non- targeted analysis
– Optimisation of sample prep, analytical instrumentation, ionisation mode,
etc. is a compromise
 Requires prior knowledge of formulation of food contact materials
 Method workflow under development among research groups
– Nerin, et al. DOI: 10.1016/j.aca.2013.02.028
– Koster, et al. DOI: 10.1080/19440049.2013.866718
– Cabovska, Waters application note 720005326en
Non intentionally added substances

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XEVO Universal source:
Compatibility Options

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 Known to migrate from poorly manufactured polyamide kitchen utensils
(black)
 Carcinogenic compounds
 EU SML (T): not detectable i.e. < 0.01 mg.kg-1 of food or food simulant
– Sum of PAAs; no definitive list, however specific compounds included in Annex
I of 10/2011/EU
 Repeat article tested at worse case scenario for foreseeable use
– e.g. spoon: in simulant B (3 % aq. acetic acid) at 100 °C for 2 hrs x 3
Primary aromatic amines (PAAs)

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 Push button
 Quick start up
 Pre optimised conditions
AcQuity QDa Detector:
An accessible mass detector

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PAAs in dyes by AcQuity QDa
Increased
Sensitivity
Selectivity
Decreased
Sample preparation

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Phthalates in distilled spirits
 Phthalates cover a large group of compounds, esters of phthalic acid
 Known toxic effects
− Considered endocrine disruptors, related to reproduction in animal studies
 Migration can occur during production and storage, from packaging materials,
coatings, equipment coatings, sealants, etc.

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Challenges in phthalate analysis
Background ~7e4
DBP at 100 ppb
 Traditionally, analysed by gas chromatography
– Derivatisation and/ or extraction required
– Non selective m/z 149 monitored for multiple compounds
 Growing interest liquid chromatography method
– Reduced sample preparation: dilute and shoot
– Improved selectivity on m/z transitions
 Ubiquitous contaminants
– Significant background impacts accurate
quantification

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Isolator column: Overview
 Ubiquitous contaminants
 AcQuity C18 isolator column
− Part number: 186004476
 Isolator separates background
contaminants from analytes of
interest
Isolator column
Sample injector
Solvent mixer

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Isolator column:
Contaminant separation
BBP
Background BBP
contaminant

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Sample Analysis
+
 Dilute 1:1 with water and place in vial for LC-MS/MS analysis
Sample Name Spirit type
1. Sample A Brandy (brand A)
2. Sample B Gin
3. Sample C
Whiskey (brand
A)
4. Sample D Brandy (brand B)
5. Sample E Tequila
6. Sample F
Whiskey (brand
B)

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Sample F spiked at 100 µg.l-1
DINP
DNOP
DEHP
BBP
DBP
DEP
DMP

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Compound name: DMP
Correlation coefficient: r = 0.997256, r^2 = 0.994520
Calibration curve: 2819.84 * x + 19543.6
Response type: External Std, Area
Curve type: Linear, Origin: Exclude, Weighting: 1/x, Axis trans: None
ppb
-0 10 20 30 40 50 60 70 80 90 100
Response
-0
100000
200000
300000
Compound name: BBP
Correlation coefficient: r = 0.997755, r^2 = 0.995515
Calibration curve: 839.103 * x + 1264.79
Response type: External Std, Area
Curve type: Linear, Origin: Exclude, Weighting: 1/x, Axis trans: None
ppb
-0 10 20 30 40 50 60 70 80 90 100
Response
-0
20000
40000
60000
80000
Matrix matched calibration curve
BBP
R2: 0.996
DMP
R2: 0.995
Compound name: DNOP
Correlation coefficient: r = 0.998477, r^2 = 0.996957
Calibration curve: 763.204 * x + 168.408
Response type: External Std, Area
Curve type: Linear, Origin: Exclude, Weighting: 1/x, Axis trans: None
ppb
-0 10 20 30 40 50 60 70 80 90 100
Response
-0
20000
40000
60000
DNOP
R2: 0.997
Phthalate
LOD
(S/N > 3)
LOQ
(S/N > 10)
DMP < 1 ppb < 1 ppb
DEP < 1 ppb < 1 ppb
DBP < 1 ppb < 1 ppb
BBP < 1 ppb < 1 ppb
DEHP < 1 ppb < 1 ppb
DNOP < 1 ppb < 1 ppb
DINP 5 ppb < 10 ppb

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System Specificity: Matrix Blanks
Blank
Spiked at 100 µg.l-1
Blank Blank
Sample A Sample C Sample E
Spiked at 100 µg.l-1 Spiked at 100 µg.l-1

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System robustness:
100 replicate injections
Name RSD %
Relative Precision
(CV)
DMP 4.55 0.05
DEP 1.87 0.02
DBP 2.05 0.02
BBP 1.95 0.02
DEHP 3.82 0.04
DNOP 5.90 0.06
DINP 4.98 0.05

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 Restricted use of BPA in
– Polycarbonate infant bottles
– Epoxy resin for sealing packaging
 BPA and family are suspected
estrogenic activity and endocrine
disruptor
Bisphenols from resins

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The advantage of RADAR
Full scan and MRM in one analysis
1. Protein precipitation
2. SPE – OASIS HLB
1. Protein precipitation
2. DisQUE (QuEChERS)
3. SPE – OASIS HLB

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Spiked Compounds
1 pg/μL in Samples
S/N > 3

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NIAS in adhesives
 Non targeted analysis of migrants from adhesives
 Headspace GC coupled with single quadrupole MS
 APGC coupled with QToF

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Atmospheric Pressure Gas Chromatography

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Source and Ion Chamber

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Charge Transfer
Dry Source
M+. produced
Plasma
Corona Pin
Sample Cone
Make-up gas (N2)

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Proton Transfer
Wet Source
M+H+ produced
Plasma
Corona Pin
Sample Cone
Make-up gas (N2)

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Xevo Tof MSE
Acquisition of the complete MS Dataset
 Low energy
Simultaneous acquisition
 Elevated energy
CE ramp applied

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Identification of Unknowns
Reproduced with thanks to Prof. Christina Nerin & group, University of Zaragoza
5-chloro-2-methyl-1,2-thiazol-3(2H)-one

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APGC-ToF vs HS-GC-EI-Q
Reproduced with thanks to Prof. Christina Nerin & group, University of Zaragoza

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Conclusions
 Vast and varied area of analysis with international interest increasing
 Extensive legislation in place
– Providing solid base for safety and analytical approach
– Exporting to different countries/ states
 Analytical challenges faced by food industry
– Important to maintain good communication between suppliers for efficient proof
of compliance
 Accessible and robust applications available for routine analysis of FCMs
– Specific migration and non-targeted (or NIAS) workflow
 Improves consumer confidence and ensures compliance for export with
high throughput

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