Combination of Standard Addition and Isotope Dilution Mass Spectrometry for the Accurate Determination of Melamine and Cyanuric Acid in Infant Formula
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reference Materials
2.2. Preparation of MEL and CYA in Infant Formula as an In–House Matrix Reference Material
2.3. Sample Preparation for LC–MS Analysis
2.4. 2D–HILIC–ESI–MS/MS Analysis
2.5. Method Validation
3. Results
3.1. Exact Matching Double IDMS (EMD–IDMS)
3.2. Matched Standard Addition–IDMS (MSA–IDMS)
3.3. Uncertainty Estimation of EMD–IDMS and MSA–IDMS
3.4. Uncertainty of EMD–IDMS of MEL/13C3–MEL of the PT Sample
3.5. Uncertainty Determination of MSA–IDMS of Neat MEL/13C3–MEL Solution in Reference Matrix
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Martin, R.E.; Hizo, C.B.; Ong, A.M.; Alba, O.M.; Ishiwata, H. Release of formaldehyde and melamine from melamine tableware manufactured in Philippines. J. Food Prot. 1992, 55, 632–635. [Google Scholar] [CrossRef] [PubMed]
- Cantú, R.; Evans, O.; Kawahara, F.K.; Wymer, L.J.; Dufour, A.P. HPLC Determination of Cyanuric Acid in Swimming Pool Waters Using Phenyl and Confirmatory Porous Graphitic Carbon Columns. Anal. Chem. 2001, 73, 3358–3364. [Google Scholar] [CrossRef] [PubMed]
- Chapman, R.P.; Averell, P.R.; Harris, R.R. Solubility of Melamine in Water. Ind. Eng. Chem. Res. 1943, 35, 137–138. [Google Scholar] [CrossRef]
- O’Malley, M. The Regulatory Evaluation of the Skin Effects of Pesticides. In Hayes’ Handbook of Pesticide Toxicology, 3rd ed.; Academic Press: Cambridge, MA, USA, 2010. [Google Scholar]
- Huq, S.W.; Bierman, J.; Koerner, P.J.; Campognone, M. Simultaneous Extraction of Melamine and Cyanuric Acid from Food Products Using Strata® Melamine SPE and Ultra–fast LC/MS/MS Analysis Using Kinetex™ HILIC, Rapid LC/MS/MS Analysis on Luna® HILIC, or Rapid GC/MS Analysis on Zebron™ ZB–XLB HT. In Rapid LC/MS/MS Analysis on Luna; TN–0021 Applications; Phenomenex Inc.: Torrance, CA, USA, 2009. [Google Scholar]
- World Health Organization. Melamine and Cyanuric acid: Toxicity, Preliminary Risk Assessment and Guidance on Levels in Food. Agric. Food Sci. Chem. Environ. Sci. 2008, 17086052. [Google Scholar]
- Sathyanarayana, S.; Flynn, J.T.; Messito, M.J.; Gross, R.; Whitlock, K.B.; Kannan, K.; Karthikraj, R.; Morrison, D.; Huie, M.; Christakis, D.; et al. Melamine and cyanuric acid exposure and kidney injury in US children. Environ. Res. 2019, 171, 18–23. [Google Scholar] [CrossRef] [PubMed]
- Hon, P.Y.; Chu, P.W.; Cheng, C.-H.; Lee, T.C.; Chan, P.-K.; Cheung, S.T.; Wong, Y.-C. Development of melamine certified reference material in milk using two different isotope dilution mass spectrometry techniques. J. Chromatogr. A 2011, 1218, 6907–6913. [Google Scholar] [CrossRef] [PubMed]
- Zhu, H.; Kannan, K. Melamine and cyanuric acid in foodstuffs from the United States and their implications for human exposure. Environ. Int. 2019, 130, 104950. [Google Scholar] [CrossRef] [PubMed]
- Takazawa, M.; Suzuki, S.; Kannan, K. Leaching of melamine and cyanuric acid from melamine–based tableware at different temperatures and water–based simulants. Environ. Chem. Ecotoxicol. 2020, 2, 91–96. [Google Scholar] [CrossRef]
- Miao, H.; Fan, S.; Wu, Y.-N.; Zhang, L.; Zhou, P.-P.; Chen, H.-J.; Zhao, Y.-F.; Li, J.-G. Simultaneous determination of melamine, ammelide, ammeline, and cyanuric acid in milk and milk products by gas chromatography–tandem mass spectrometry. Biomed. Environ. Sci. 2009, 22, 87–94. [Google Scholar] [CrossRef]
- Garber, E.A.E.; Brewer, V.A. Enzyme–linked immunosorbent assay detection of melamine in infant formula and wheat food products. J. Food Prot. 2010, 73, 701–707. [Google Scholar] [CrossRef]
- Broszat, M.; Brämer, M.; Spangenberg, B. Eine Neue Dünnschicht–Chromatographische Methode zur Bestimmung von Melamin und Cyanursaure in Milch. Analytik News 2009. Available online: https://www.researchgate.net/publication/235708518_Melamin_in_Milch_Eine_neue_dunnschicht-chromatographische_Methode_zur_Bestimmung_von_Melamin_und_Cyanursaure_in_Milch (accessed on 18 June 2024).
- Duong, V.-A.; Park, J.-M.; Lee, H. Review of Three–Dimensional Liquid Chromatography Platforms for Bottom–Up Proteomics. Int. J. Mol. Sci. 2020, 21, 1524. [Google Scholar] [CrossRef] [PubMed]
- Li, X.Q.; Zhang, Q.H.; Yang, Z.; Li, H.M.; Huang, D.F. The effects of isotope–labeled analogs on the LC–IDMS measurement by comparison of ESI responses and matrix effect of melamine, 13C3–melamine, 13C3+15N3–melamine, and 15N3–melamine. Anal. Bioanal. Chem. 2017, 409, 3233–3243. [Google Scholar] [CrossRef] [PubMed]
- Comité Consultatif pour la Quantité de Matiere. Rapport de la 1er Session; BIPM: Sèvre, France, 1995. [Google Scholar]
- Milton, M.J.T.; Quinn, T.J. Primary methods for the measurement of amount of substance. Metrologia 2001, 38, 289–296. [Google Scholar] [CrossRef]
- Sargent, M.; Harrington, C.; Harte, R. Guidelines for Achieving High Accuracy in Isotope Dilution Mass Spectrometry (IDMS); Laboratory of the Government Chemist by the Royal Society of Chemistry: Cambridge, UK, 2002; ISBN 0-85404-418-3. [Google Scholar]
- Rienitz, O.; Schiel, D.; Güttler, B.; Koch, M.; Borchers, U. A convenient and economic approach to achieve SI–traceable reference values to be used in drinking–water interlaboratory comparisons. Accredit. Qual. Assur. 2007, 12, 615–622. [Google Scholar] [CrossRef]
- Pagliano, E.; Meija, J. Reducing the matrix effects in chemical analysis: Fusion of isotope dilution and standard addition methods. Metrologia 2016, 53, 829–834. [Google Scholar] [CrossRef]
- Brauckmann, C.; Pramann, A.; Rienitz, O.; Schulze, A.; Phukphatthanachai, P.; Vogl, J. Combining Isotope Dilution and Standard Addition—Elemental Analysis in Complex Samples. Molecules 2021, 26, 2649. [Google Scholar] [CrossRef] [PubMed]
- Desmarchelier, A.; Cuadra, M.G.; Delatour, T.; Mottier, P. Simultaneous quantitative determination of melamine and cyanuric acid in cow’s milk and milk–based infant formula by liquid chromatography–electrospray ionization tandem mass spectrometry. J. Agric. Food Chem. 2009, 57, 7186–7193. [Google Scholar] [CrossRef] [PubMed]
- Koh, G.; Chia, R.S.C.; Lin, Q.; Cheow, P.; Teo, T.; Lee, T. Determination of melamine in milk powder using gas chromatography–high-resolution isotope dilution mass spectrometry. J. Sep. Sci. 2011, 34, 3043–3052. [Google Scholar] [CrossRef]
- Vogl, J.; Pritzkow, W. Isotope Dilution Mass Spectrometry—A Primary Method of Measurement and Its Role for RM Certification. J. Metrol. Soc. India 2010, 25, 135–164. [Google Scholar] [CrossRef]
- Vogl, J. Measurement uncertainty in single, double and triple isotope dilution mass spectrometry. Rapid Commun. Mass Spectrom. 2012, 26, 275–281. [Google Scholar] [CrossRef]
- Frank, C.; Rienitz, O.; Swart, C.; Schiel, D. Improving species–specific IDMS: The advantages of triple IDMS. Anal. Bioanal. Chem. 2012, 405, 1913–1919. [Google Scholar] [CrossRef] [PubMed]
- Ellison, S.L.R.; Roesslein, M.; Williams, A. EURACHEM/CITAC Guide Quantifying Uncertainty in Analytical Measurement, 3rd ed.; Eurachem/CITAC: Teddington, UK, 2012; ISBN 0948926155. [Google Scholar]
- De Bièvre, P.; Peiser, H.S. Basic equations and uncertainties in isotope–dilution mass spectrometry for traceability to SI of values obtained by this primary method. Fresenius J. Anal. Chem. 1997, 359, 523–525. [Google Scholar] [CrossRef]
- Henrion, A. Reduction of systematic errors in quantitative analysis by isotope dilution mass spectrometry (IDMS): An iterative method. Fresenius J. Anal. Chem. 1994, 350, 657–658. [Google Scholar] [CrossRef]
- Reichmuth, A.; Wunderli, S.; Weber, M.; Meyer, V.R. The uncertainty of weighing data obtained with electronic analytical balances. Microchim. Acta 2004, 148, 133–141. [Google Scholar] [CrossRef]
- Breidbach, A.; Ulberth, F. Two–dimensional heart–cut LC–LC improves accuracy of exact–matching double isotope dilution mass spectrometry measurements of aflatoxin B1 n cereal–based baby food, maize, and maize–based feed. Anal. Bioanal. Chem. 2015, 407, 3159–3167. [Google Scholar] [CrossRef]
- Koehling, R.; Hellriegel, C. Characterization of Stable Isotope Caffeine as Reference Material for Isotope Dilution Mass Spectrometry. Analytix 2015, 2. Available online: https://www.sigmaaldrich.com/CH/de/technical-documents/technical-article/analytical-chemistry/caffeine-tracecert-crm-mass-spectrometry (accessed on 18 June 2024).
- Mackay, L.G.; Taylor, C.P.; Myors, R.B.; Hearn, R.; King, B. High accuracy analysis by isotope dilution mass spectrometry using an iterative exact matching technique. Accredit. Qual. Assur. 2003, 8, 191–194. [Google Scholar] [CrossRef]
- BIPM; IEC; IFCC; ILAC; ISO; IUPAC; IUPAP; OIML. Evaluation of measurement data—Guide to the expression of uncertainty in measurement. Jt. Comm. Guides Metrol. 2008, 100. Available online: https://www.bipm.org/documents/20126/2071204/JCGM_100_2008_E.pdf/cb0ef43f-baa5-11cf-3f85-4dcd86f77bd6?version=1.10&t=1659082531978&download=true (accessed on 18 June 2024).
- R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2023; Available online: https://www.R-project.org/ (accessed on 14 January 2024).
- World Health Organization (WHO). Report of a WHO Expert Meeting in Collaboration with FAO Supported by Health Canada; Health Canada: Ottawa, ON, Canada, 2009; ISBN 978 92 4 159795 1.
Name | Precursor Ion [m/z] | Product Ion [m/z] | RT min | Ion Polarity | Collision Energy V | Fragmentor V |
---|---|---|---|---|---|---|
CYA | 128.0 | 42.0 | 2.7 | negative | 12 | 50 |
13C3–CYA | 131.0 | 43.1 | 2.7 | negative | 12 | 50 |
MEL | 127.0 | 85.0 | 6.7 | positive | 16 | 113 |
13C3–MEL | 130.1 | 86.9 | 6.7 | positive | 16 | 113 |
Measurand | Mean | u | Monte Carlo Simulation ANOVA (Relative Contributions in %) | GUM ci | GUM Index (ur2 in %) |
---|---|---|---|---|---|
mX/mg | 500 | 0.144 | 0.01 | −0.025 | 0.0047 |
mY/mg | 594 | 0.229 | 0.01 | 0.021 | 0.0085 |
mZc/mg | 595 | 0.172 | 0.01 | 0.021 | 0.0048 |
mYc/mg | 598 | 0.173 | 0.01 | −0.021 | 0.0048 |
RB | 1.02 | 0.025 | 34.31 | 12.000 | 34.0000 |
RBc | 0.97 | 0.030 | 54.37 | −13.000 | 55.0000 |
wZc/mg/kg | 10.0 | 0.14 | 11.13 | 1.2 | 11.0000 |
Residual | – | – | 0.16 | – | – |
MEL | CYA | |
---|---|---|
<Rb,i> | 1.221 ± 0.008 (0.6%) | 1.056 ± 0.008 (0.8%) |
urel (Rb,i) | 3.7% | 1.7% |
a0/a1 | 1.003 ± 0.034 (MCS) | 0.994 ± 0.017 |
Measurand | Mean | u | ci | ci2·ur2/10−5 | Index |
---|---|---|---|---|---|
mx,1/mg | 48.510 | 0.049 | 1.00 | 0.10 | 0.2% |
my,1/mg | 49.002 | 0.049 | 1.00 | 0.10 | 0.2% |
mz,1/mg | 0.000 | – | – | – | – |
Rb,1 | 1.217 | 0.013 | 0.58 | 3.90 | 8.4% |
mx,2/mg | 49.523 | 0.050 | 1.00 | 0.10 | 0.2% |
my,2/mg | 99.193 | 0.099 | 1.00 | 0.10 | 0.2% |
mz,2/mg | 49.053 | 0.049 | 1.00 | 0.10 | 0.2% |
Rb,2 | 1.231 | 0.038 | 0.58 | 32.20 | 69.4% |
mx,3/mg | 48.851 | 0.049 | 1.00 | 0.10 | 0.2% |
my,3/mg | 147.450 | 0.147 | 1.00 | 0.10 | 0.2% |
mz,3/mg | 98.266 | 0.098 | 1.00 | 0.10 | 0.2% |
Rb,3 | 1.224 | 0.020 | 0.58 | 8.50 | 18.3% |
mx,4/mg | 47.388 | 0.047 | 1.00 | 0.10 | 0.2% |
my,4/mg | 198.577 | 0.199 | 1.00 | 0.10 | 0.2% |
mz,4/mg | 148.252 | 0.148 | 1.00 | 0.10 | 0.2% |
Rb,4 | 1.213 | 0.005 | 0.58 | 0.67 | 1.5% |
Measurand | Mean | u | ci | ci2·ur2/10−5 | Index |
---|---|---|---|---|---|
mx,1/mg | 48.695 | 0.049 | 1.00 | 0.10 | 1.0% |
my,1/mg | 48.943 | 0.049 | 1.00 | 0.10 | 1.0% |
mz,1/mg | 0.000 | – | – | – | – |
Rb,1 | 1.051 | 0.007 | 0.58 | 1.28 | 12.3% |
mx,2/mg | 48.218 | 0.048 | 1.00 | 0.10 | 1.0% |
my,2/mg | 98.725 | 0.099 | 1.00 | 0.10 | 1.0% |
mz,2/mg | 48.900 | 0.049 | 1.00 | 0.10 | 1.0% |
Rb,2 | 1.048 | 0.003 | 0.58 | 0.34 | 3.2% |
mx,3/mg | 49.055 | 0.049 | 1.00 | 0.10 | 1.0% |
my,3/mg | 147.418 | 0.147 | 1.00 | 0.10 | 1.0% |
mz,3/mg | 98.247 | 0.098 | 1.00 | 0.10 | 1.0% |
Rb,3 | 1.067 | 0.014 | 0.58 | 5.67 | 54.5% |
mx,4/mg | 48.991 | 0.049 | 1.00 | 0.10 | 1.0% |
my,4/mg | 197.813 | 0.198 | 1.00 | 0.10 | 1.0% |
mz,4/mg | 147.505 | 0.148 | 1.00 | 0.10 | 1.0% |
Rb,4 | 1.057 | 0.008 | 0.58 | 2.01 | 19.4% |
Measurand | Value | u | ci | ci2·ur2/10−5 | Index |
---|---|---|---|---|---|
mx1 | 500.770 | 0.501 | 1.00 | 0.10 | 0.12% |
my1 | 99.340 | 0.099 | 1.00 | 0.10 | 0.12% |
mz1 | 0.000 | 0.000 | – | 0.00 | – |
Rb,1 | 10.428 | 0.209 | 0.71 | 20.00 | 24.60% |
mx2 | 502.790 | 0.503 | 1.00 | 0.10 | 0.12% |
my2 | 101.460 | 0.101 | 1.00 | 0.10 | 0.12% |
mz2 | 49.430 | 0.049 | 1.00 | 0.10 | 0.12% |
Rb,2 | 10.877 | 0.218 | 0.71 | 20.00 | 24.60% |
mx3 | 500.760 | 0.501 | 1.00 | 0.10 | 0.12% |
my3 | 100.460 | 0.100 | 1.00 | 0.10 | 0.12% |
mz3 | 99.320 | 0.099 | 1.00 | 0.10 | 0.12% |
Rb,3 | 11.787 | 0.236 | 0.71 | 20.00 | 24.60% |
mx4 | 507.570 | 0.508 | 1.00 | 0.10 | 0.12% |
my4 | 100.670 | 0.101 | 1.00 | 0.10 | 0.12% |
mz4 | 149.410 | 0.149 | 1.00 | 0.10 | 0.12% |
Rb,4 | 12.822 | 0.256 | 0.71 | 20.00 | 24.60% |
wz | 10.080 | 0.020 | 0.71 | 0.20 | 0.25% |
MCS | GUM | |
---|---|---|
a0 | 2.0534 ± 0.0355 | 2.0541 ± 0.0359 |
a1 | 1.6202 ± 0.2101 | 1.617 ± 0.211 |
Index (Rb,1) | 24.7% | 41.0% |
Index (Rb,2) | 24.7% | 6.3% |
Index (Rb,3) | 24.7% | 3.8% |
Index (Rb,4) | 24.7% | 48.4% |
wX/mg/kg (95% confidence, k = 2) | 12.8 [+4.8, −2.9] | 12.8 ± 3.7 |
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Pedan, V.; Koehling, R.; Drexel, L.; Breitruck, K.; Rueck, A.; Rohn, S.; Rienitz, O.; Pramann, A.; Seidel, T.; Allenspach, E.; et al. Combination of Standard Addition and Isotope Dilution Mass Spectrometry for the Accurate Determination of Melamine and Cyanuric Acid in Infant Formula. Foods 2024, 13, 2377. https://doi.org/10.3390/foods13152377
Pedan V, Koehling R, Drexel L, Breitruck K, Rueck A, Rohn S, Rienitz O, Pramann A, Seidel T, Allenspach E, et al. Combination of Standard Addition and Isotope Dilution Mass Spectrometry for the Accurate Determination of Melamine and Cyanuric Acid in Infant Formula. Foods. 2024; 13(15):2377. https://doi.org/10.3390/foods13152377
Chicago/Turabian StylePedan, Vasilisa, Rudolf Koehling, Lukas Drexel, Kathrin Breitruck, Alexander Rueck, Sascha Rohn, Olaf Rienitz, Axel Pramann, Tim Seidel, Eric Allenspach, and et al. 2024. "Combination of Standard Addition and Isotope Dilution Mass Spectrometry for the Accurate Determination of Melamine and Cyanuric Acid in Infant Formula" Foods 13, no. 15: 2377. https://doi.org/10.3390/foods13152377