Login | Register

Development of LC-HRMS Assay for the Measurement of 12 Mycotoxins in Urine

Title:

Development of LC-HRMS Assay for the Measurement of 12 Mycotoxins in Urine

Mirabi, Melika (2022) Development of LC-HRMS Assay for the Measurement of 12 Mycotoxins in Urine. Masters thesis, Concordia University.

[thumbnail of Mirabi_MSc_S2022.pdf]
Text (application/pdf)
Mirabi_MSc_S2022.pdf - Accepted Version
Restricted to Repository staff only until 1 May 2024.
Available under License Spectrum Terms of Access.
6MB

Abstract

Mycotoxins are the secondary metabolites of certain molds. These toxic compounds naturally contaminate food products and beverages and can cause severe health effects in humans and animals. Environmental changes and industrialization are currently promoting the spread of these mycotoxins worldwide. Health Canada regularly monitors the levels of specific mycotoxins in various food products. Complementarily to food monitoring, periodic biomonitoring is especially important to determine the exposure to mycotoxins in the Canadian population considering the variability of individual diets and metabolism. Urine biomonitoring is a non-invasive approach and sample collection is easy. The purpose of this study is to develop a sensitive and accurate LC-HRMS method for the detection in urine of 12 mycotoxins that impact human health. These mycotoxins are enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), alternariol (AOH), alternariol monomethyl ether (AME), beauvericin (BEA), citrinin (CIT), fumonisin B1 (FB1), fumonisin B2 (FB2), ochratoxin A (OTA) and ochratoxin alpha (OTα). The final 24-min LC-HRMS method used CORTECS T3 reversed-phase separation and employed time-segmented polarity switching to cover the 12 analytes of interest in a single analysis. To allow high-throughput for large-scale monitoring, two sample preparation procedures were evaluated: "dilute-and-shoot" and solid-phase extraction with hydrophilic and lipophilic sorbent (HLB SPE). Evaluation of solubility and non-specific adsorption with the dilute-and-shoot method revealed that enniatins (ENNs) and BEA have low solubility in a highly aqueous solvent (H2O/ACN/FA 94/5/1 v/v) with a 70-98% decrease in signal intensity compared to a highly organic solvent (MeOH/ H2O/ FA 60/39/1 v/v). This issue also caused loss of ENNs and BEA during storage of urine samples in plastic containers. Rinsing the containers with MeOH allowed the recovery of 17, 30, 57, 44 and 67% of ENNB, ENNB1, ENNA, ENNA1, and BEA, respectively. Use of 20x dilution in the dilute-and-shoot method resulted in LOQs > 2 ng/mL for almost all mycotoxins, which are present at < 1 ng/mL in real samples. Thus, dilute-and-shoot is not sensitive enough for the intended application, so HLB SPE was used for sample clean-up and enrichment. This sample preparation method recovered 68 - 88% of all the mycotoxins tested with 10x enrichment, which led to significant ionization suppression of CIT, OTα, OTA, AOH, AME and FB1. Reducing their enrichment decreased the matrix effects for all the mycotoxins (77% - 150%) except for AOH (22%) and AME (66%), which was compensated for by the addition of an internal standard (AMEd3). An optimized HLB SPE LC-HRMS method is proposed for validation and further application to real samples in the biomonitoring of mycotoxins in urine.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Mirabi, Melika
Institution:Concordia University
Degree Name:M. Sc.
Program:Chemistry
Date:24 April 2022
Thesis Supervisor(s):Vuckovic, Dajana
Keywords:Mycotoxin, LC-MS, LCHRMS, QTOF, Polarity-switching, Urine biomonitoring, HLB SPE, Dilute-and-shoot
ID Code:990588
Deposited By: Melika Mirabi
Deposited On:16 Jun 2022 14:53
Last Modified:16 Jun 2022 14:53
Additional Information:The copyright licenses of the figures are available.

References:

1. Bennett, J.; Klich, M., Mycotoxins, 16 Clin. Microbiol. Rev 2003, 497, 498.
2. Bennett, J., Mycotoxins, mycotoxicoses, mycotoxicology andMycopathologia. Springer: 1987; Vol. 100, pp 3-5.
3. Zain, M. E., Impact of mycotoxins on humans and animals. Journal of Saudi chemical society 2011, 15 (2), 129-144.
4. Capriotti, A. L.; Caruso, G.; Cavaliere, C.; Foglia, P.; Samperi, R.; Laganà, A., Multiclass mycotoxin analysis in food, environmental and biological matrices with chromatography/mass spectrometry. Mass spectrometry reviews 2012, 31 (4), 466-503.
5. Stępień, Ł.; Waśkiewicz, A., Sequence divergence of the enniatin synthase gene in relation to production of beauvericin and enniatins in Fusarium species. Toxins 2013, 5 (3), 537-555.
6. Brase, S.; Encinas, A.; Keck, J.; Nising, C. F., Chemistry and biology of mycotoxins and related fungal metabolites. Chemical reviews 2009, 109 (9), 3903-3990.
7. Yang, Y.; Li, G.; Wu, D.; Liu, J.; Li, X.; Luo, P.; Hu, N.; Wang, H.; Wu, Y., Recent advances on toxicity and determination methods of mycotoxins in foodstuffs. Trends in food science & Technology 2020, 96, 233-252.
8. Alshannaq, A.; Yu, J.-H., Occurrence, toxicity, and analysis of major mycotoxins in food. International journal of environmental research and public health 2017, 14 (6), 632.
9. Ostry, V.; Malir, F.; Toman, J.; Grosse, Y., Mycotoxins as human carcinogens—the IARC Monographs classification. Mycotoxin research 2017, 33 (1), 65-73.
10. Coppa, C. F. S. C.; Khaneghah, A. M.; Alvito, P.; Assunção, R.; Martins, C.; Eş, I.; Gonçalves, B. L.; de Neeff, D. V.; Sant'Ana, A. S.; Corassin, C. H., The occurrence of mycotoxins in breast milk, fruit products and cereal-based infant formula: A review. Trends in Food Science & Technology 2019, 92, 81-93.
11. Khodaei, D.; Javanmardi, F.; Khaneghah, A. M., The global overview of the occurrence of mycotoxins in cereals: a three-year survey. Current Opinion in Food Science 2021, 39, 36-42.
12. Murphy, P. A.; Hendrich, S.; Landgren, C.; Bryant, C. M., Food mycotoxins: an update. Journal of food science 2006, 71 (5), R51-R65.
13. Jestoi, M., Emerging Fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin—A review. Critical reviews in food science and nutrition 2008, 48 (1), 21-49.
14. Sá, S. V. d.; Monteiro, C.; Fernandes, J. O.; Pinto, E.; Faria, M. A.; Cunha, S. C., Emerging mycotoxins in infant and children foods: A review. Critical Reviews in Food Science and Nutrition 2021, 1-15.
15. Ostry, V.; Malir, F.; Ruprich, J., Producers and important dietary sources of ochratoxin A and citrinin. Toxins 2013, 5 (9), 1574-1586.
16. Logrieco, A.; Rizzo, A.; Ferracane, R.; Ritieni, A., Occurrence of beauvericin and enniatins in wheat affected by Fusarium avenaceum head blight. Applied and Environmental Microbiology 2002, 68 (1), 82-85.
17. Morrison, E.; Kosiak, B.; Ritieni, A.; Aastveit, A. H.; Uhlig, S.; Bernhoft, A., Mycotoxin production by Fusarium avenaceum strains isolated from Norwegian grain and the cytotoxicity of rice culture extracts to porcine kidney epithelial cells. Journal of Agricultural and Food Chemistry 2002, 50 (10), 3070-3075.
18. Logrieco, A.; Moretti, A.; Castella, G.; Kostecki, M.; Golinski, P.; Ritieni, A.; Chelkowski, J., Beauvericin production by Fusarium species. Applied and Environmental Microbiology 1998, 64 (8), 3084-3088.
19. Ross, P.; Nelson, P.; Richard, J.; Osweiler, G.; Rice, L.; Plattner, R.; Wilson, T. M., Production of fumonisins by Fusarium moniliforme and Fusarium proliferatum isolates associated with equine leukoencephalomalacia and a pulmonary edema syndrome in swine. Applied and Environmental Microbiology 1990, 56 (10), 3225-3226.
20. Ross, P. F.; Rice, L. G.; Osweiler, G. D.; Nelson, P. E.; Richard, J. L.; Wilson, T. M., A review and update of animal toxicoses associated with fumonisin-contaminated feeds and production of fumonisins by Fusarium isolates. Mycopathologia 1992, 117 (1), 109-114.
21. Rheeder, J. P.; Marasas, W. F.; Vismer, H. F., Production of fumonisin analogs by Fusarium species. Applied and environmental microbiology 2002, 68 (5), 2101-2105.
22. Ostry, V., Alternaria mycotoxins: an overview of chemical characterization, producers, toxicity, analysis and occurrence in foodstuffs. World Mycotoxin Journal 2008, 1 (2), 175-188.
23. Bullerman, L. B.; Bianchini, A., Stability of mycotoxins during food processing. International journal of food microbiology 2007, 119 (1-2), 140-146.
24. Richard, J. L., Some major mycotoxins and their mycotoxicoses—An overview. International journal of food microbiology 2007, 119 (1-2), 3-10.
25. (FDA), F. a. D. A. Mycotoxins in domestic and imported foods https://www.fda.gov/media/140749/download.
26. Commission, E., Setting maximum levels for certain contaminants in foodstuffs. Official Journal of the European Union 2006.
27. Wielogorska, E.; Mooney, M.; Eskola, M.; Ezekiel, C. N.; Stranska, M.; Krska, R.; Elliott, C., Occurrence and human-health impacts of mycotoxins in Somalia. Journal of agricultural and food chemistry 2019, 67 (7), 2052-2060.
28. Canada, H. Information Document on Health Canada’s Proposed Maximum Limits (Standards) for the Presence of the Mycotoxin Ochratoxin A in Foods. https://www.canada.ca/en/health-canada/services/food-nutrition/public-involvement-partnerships/information-document-proposed-maximum-limits-standards-presence-mycotoxin-ochratoxin-foods.html (accessed February 28, 2022).
29. Do, T. H.; Tran, S. C.; Le, C. D.; Nguyen, H.-B. T.; Le, P.-T. T.; Le, H.-H. T.; Le, T. D.; Thai-Nguyen, H.-T., Dietary exposure and health risk characterization of aflatoxin B1, ochratoxin A, fumonisin B1, and zearalenone in food from different provinces in Northern Vietnam. Food Control 2020, 112, 107108.
30. Pfohl‐Leszkowicz, A.; Manderville, R. A., Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans. Molecular nutrition & food research 2007, 51 (1), 61-99.
31. Shephard, G. S.; Thiel, P.; Sydenham, E. W., Initial studies on the toxicokinetics of fumonisin B1 in rats. Food and Chemical Toxicology 1992, 30 (4), 277-279.
32. Turksoy, S.; Kabak, B., Determination of aflatoxins and ochratoxin A in wheat from different regions of Turkey by HPLC with fluorescence detection. Acta Alimentaria 2020, 49 (1), 118-124.
33. Hassan, Z. U.; Al-Thani, R. F.; Migheli, Q.; Jaoua, S., Detection of toxigenic mycobiota and mycotoxins in cereal feed market. Food Control 2018, 84, 389-394.
34. Shi, H.; Schwab, W.; Yu, P., Natural occurrence and co-contamination of twelve mycotoxins in industry-submitted cool-season cereal grains grown under a low heat unit climate condition. Toxins 2019, 11 (3), 160.
35. Silva, L. J.; Pereira, A. M.; Pena, A.; Lino, C. M., Citrinin in foods and supplements: a review of occurrence and analytical methodologies. Foods 2021, 10 (1), 14.
36. Silva, L. J.; Pereira, A. M.; Pena, A.; Lino, C. M., Citrinin in foods and supplements: A review of occurrence and analytical methodologies. Foods 2020, 10 (1), 14.
37. Jeswal, P.; Kumar, D., Mycobiota and natural incidence of aflatoxins, ochratoxin A, and citrinin in Indian spices confirmed by LC-MS/MS. International journal of microbiology 2015, 2015.
38. Zhang, H.; Ahima, J.; Yang, Q.; Zhao, L.; Zhang, X.; Zheng, X., A review on citrinin: Its occurrence, risk implications, analytical techniques, biosynthesis, physiochemical properties and control. Food Research International 2021, 141, 110075.
39. Santini, A.; Meca, G.; Uhlig, S.; Ritieni, A., Fusaproliferin, beauvericin and enniatins: occurrence in food–a review. World Mycotoxin Journal 2012, 5 (1), 71-81.
40. Gautier, C.; Pinson-Gadais, L.; Richard-Forget, F., Fusarium mycotoxins enniatins: An updated review of their occurrence, the producing Fusarium species, and the abiotic determinants of their accumulation in crop harvests. Journal of Agricultural and Food Chemistry 2020, 68 (17), 4788-4798.
41. Luz, C.; Saladino, F.; Luciano, F.; Mañes, J.; Meca, G., Occurrence, toxicity, bioaccessibility and mitigation strategies of beauvericin, a minor Fusarium mycotoxin. Food and Chemical Toxicology 2017, 107, 430-439.
42. Reddy, L.; Bhoola, K., Ochratoxins—Food contaminants: Impact on human health. Toxins 2010, 2 (4), 771-779.
43. Di Paolo, N.; Guarnieri, A.; Loi, F.; Sacchi, G.; Mangiarotti, A.; Di Paolo, M., Acute renal failure from inhalation of mycotoxins. Nephron 1993, 64 (4), 621-625.
44. Pfohl-Leszkowicz, A.; Grosse, Y.; Castegnaro, M.; Nicolov, I.; Chernozemsky, I.; Bartsch, H.; Betbeder, A.; Creppy, E.; Dirheimer, G., Ochratoxin A-related DNA adducts in urinary tract tumours of Bulgarian subjects. IARC scientific publications 1993, (124), 141-148.
45. Peraica, M.; Domijan, A.-M.; Miletić-Medved, M.; Fuchs, R., The involvement of mycotoxins in the development of endemic nephropathy. Wiener Klinische Wochenschrift 2008, 120 (13), 402-407.
46. Reddy, B.; Raghavender, C., Outbreaks of fusarial-toxicoses in India. Cereal research communications 2008, 36 (Supplement-6), 321-325.
47. Voss, K.; Smith, G.; Haschek, W., Fumonisins: Toxicokinetics, mechanism of action and toxicity. Animal feed science and technology 2007, 137 (3-4), 299-325.
48. Riley, R. T.; Voss, K. A., Differential sensitivity of rat kidney and liver to fumonisin toxicity: organ-specific differences in toxin accumulation and sphingoid base metabolism. Toxicological Sciences 2006, 92 (1), 335-345.
49. Flajs, D.; Peraica, M., Toxicological properties of citrinin. Archives of Industrial Hygiene and Toxicology 2009, 60 (4), 457-464.
50. Speijers, G. J. A.; Speijers, M. H. M., Combined toxic effects of mycotoxins. Toxicology letters 2004, 153 (1), 91-98.
51. Liu, G.; Qian, Y.; Zhang, P.; Dong, W.; Qi, Y.; Guo, H., Etiological role of Alternaria alternata in human esophageal cancer. Chinese medical journal 1992, 105 (5), 394-400.
52. https://www.lookchem.com/Chempedia/Chemical-Resource/Chemical-DataBase/13857.html (accessed April 24, 2022).
53. https://www.chemsrc.com/ (accessed April 24).
54. Ren, Y.; Zhang, Y.; Han, S.; Han, Z.; Wu, Y., Simultaneous determination of fumonisins B1, B2 and B3 contaminants in maize by ultra high-performance liquid chromatography tandem mass spectrometry. Analytica chimica acta 2011, 692 (1-2), 138-145.
55. https://www.caymanchem.com/ (accessed January 24).
56. https://pubchem.ncbi.nlm.nih.gov/ https://pubchem.ncbi.nlm.nih.gov/ (accessed August 20, 2021).
57. Arce-López, B.; Lizarraga, E.; Vettorazzi, A.; González-Peñas, E., Human biomonitoring of mycotoxins in blood, plasma and serum in recent years: a review. Toxins 2020, 12 (3), 147.
58. Baig, A., Biochemical composition of normal urine. Nature Precedings 2011, 1-1.
59. Robinson-Cohen, C.; Ix, J. H.; Smits, G.; Persky, M.; Chertow, G. M.; Block, G. A.; Kestenbaum, B. R., Estimation of 24-hour urine phosphate excretion from spot urine collection: development of a predictive equation. Journal of Renal Nutrition 2014, 24 (3), 194-199.
60. Taylor, E. N.; Curhan, G. C., Differences in 24-hour urine composition between black and white women. Journal of the American Society of Nephrology 2007, 18 (2), 654-659.
61. Boeniger, M. F.; Lowry, L. K.; Rosenberg, J., Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. American Industrial Hygiene Association journal 1993, 54 (10), 615-627.
62. Cocchetto, D. M.; Tschanz, C.; Bjornsson, T. D., Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance. Therapeutic drug monitoring 1983, 5 (2), 161-168.
63. Narayanan, S.; Appleton, H., Creatinine: a review. Clinical chemistry 1980, 26 (8), 1119-1126.
64. Adedeji, A. O.; Pourmohamad, T.; Chen, Y.; Burkey, J.; Betts, C. J.; Bickerton, S. J.; Sonee, M.; McDuffie, J. E., Investigating the value of urine volume, creatinine, and cystatin C for urinary biomarkers normalization for drug development studies. International journal of toxicology 2019, 38 (1), 12-22.
65. Singh, J.; Mehta, A., Rapid and sensitive detection of mycotoxins by advanced and emerging analytical methods: A review. Food science & nutrition 2020, 8 (5), 2183-2204.
66. Pallarés, N.; Carballo, D.; Ferrer, E.; Rodríguez-Carrasco, Y.; Berrada, H., High-Throughput Determination of Major Mycotoxins with Human Health Concerns in Urine by LC-Q TOF MS and Its Application to an Exposure Study. Toxins 2022, 14 (1), 42.
67. Šarkanj, B.; Ezekiel, C. N.; Turner, P. C.; Abia, W. A.; Rychlik, M.; Krska, R.; Sulyok, M.; Warth, B., Ultra-sensitive, stable isotope assisted quantification of multiple urinary mycotoxin exposure biomarkers. Analytica chimica acta 2018, 1019, 84-92.
68. Ediage, E. N.; Di Mavungu, J. D.; Song, S.; Wu, A.; Van Peteghem, C.; De Saeger, S., A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry. Analytica chimica acta 2012, 741, 58-69.
69. Escrivá, L.; Manyes, L.; Font, G.; Berrada, H., Mycotoxin analysis of human urine by LC-MS/MS: A comparative extraction study. Toxins 2017, 9 (10), 330.
70. Silva, L. J.; Pena, A.; Lino, C. M.; Fernández, M. F.; Mañes, J., Fumonisins determination in urine by LC-MS-MS. Analytical and bioanalytical chemistry 2010, 396 (2), 809-816.
71. Fan, K.; Xu, J.; Jiang, K.; Liu, X.; Meng, J.; Di Mavungu, J. D.; Guo, W.; Zhang, Z.; Jing, J.; Li, H., Determination of multiple mycotoxins in paired plasma and urine samples to assess human exposure in Nanjing, China. Environmental pollution 2019, 248, 865-873.
72. Huybrechts, B.; Martins, J.; Debongnie, P.; Uhlig, S.; Callebaut, A., Fast and sensitive LC–MS/MS method measuring human mycotoxin exposure using biomarkers in urine. Archives of toxicology 2015, 89 (11), 1993-2005.
73. Gerding, J.; Cramer, B.; Humpf, H. U., Determination of mycotoxin exposure in Germany using an LC‐MS/MS multibiomarker approach. Molecular nutrition & food research 2014, 58 (12), 2358-2368.
74. Warth, B.; Petchkongkaew, A.; Sulyok, M.; Krska, R., Utilising an LC-MS/MS-based multi-biomarker approach to assess mycotoxin exposure in the Bangkok metropolitan area and surrounding provinces. Food Additives & Contaminants: Part A 2014, 31 (12), 2040-2046.
75. Slobodchikova, I. Multi-Class Liquid Chromatography-High Resolution Mass Spectrometry Methods for Monitoring of Mycotoxins and Metabolites in Human Plasma for Exposure Studies. Concordia University, 2020.
76. Viegas, S.; Assunção, R.; Martins, C.; Nunes, C.; Osteresch, B.; Twarużek, M.; Kosicki, R.; Grajewski, J.; Ribeiro, E.; Viegas, C., Occupational exposure to mycotoxins in swine production: Environmental and biological monitoring approaches. Toxins 2019, 11 (2), 78.
77. Pena, A.; Seifrtová, M.; Lino, C.; Silveira, I.; Solich, P., Estimation of ochratoxin A in portuguese population: New data on the occurrence in human urine by high performance liquid chromatography with fluorescence detection. Food and Chemical Toxicology 2006, 44 (9), 1449-1454.
78. Ahn, J.; Kim, D.; Kim, H.; Jahng, K.-Y., Quantitative determination of mycotoxins in urine by LC-MS/MS. Food Additives & Contaminants: Part A 2010, 27 (12), 1674-1682.
79. Rubert, J.; Soriano, J. M.; Mañes, J.; Soler, C., Rapid mycotoxin analysis in human urine: a pilot study. Food and Chemical Toxicology 2011, 49 (9), 2299-2304.
80. Desalegn, B.; Nanayakkara, S.; Harada, K. H.; Hitomi, T.; Chandrajith, R.; Karunaratne, U.; Abeysekera, T.; Koizumi, A., Mycotoxin detection in urine samples from patients with chronic kidney disease of uncertain etiology in Sri Lanka. Bulletin of Environmental Contamination and Toxicology 2011, 87 (1), 6-10.
81. Klapec, T.; Šarkanj, B.; Banjari, I.; Strelec, I., Urinary ochratoxin A and ochratoxin alpha in pregnant women. Food and chemical toxicology 2012, 50 (12), 4487-4492.
82. Abia, W. A.; Warth, B.; Sulyok, M.; Krska, R.; Tchana, A.; Njobeh, P. B.; Turner, P. C.; Kouanfack, C.; Eyongetah, M.; Dutton, M., Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach. Food and chemical toxicology 2013, 62, 927-934.
83. Solfrizzo, M.; Gambacorta, L.; Visconti, A., Assessment of multi-mycotoxin exposure in southern Italy by urinary multi-biomarker determination. Toxins 2014, 6 (2), 523-538.
84. Franco, L. T.; Petta, T.; Rottinghaus, G. E.; Bordin, K.; Gomes, G. A.; Alvito, P.; Assunção, R.; Oliveira, C. A., Assessment of mycotoxin exposure and risk characterization using occurrence data in foods and urinary biomarkers in Brazil. Food and chemical toxicology 2019, 128, 21-34.
85. Qiao, X.; Zhang, J.; Yang, Y.; Yin, J.; Li, H.; Xing, Y.; Shao, B., Development of a simple and rapid LC-MS/MS method for the simultaneous quantification of five Alternaria mycotoxins in human urine. Journal of Chromatography B 2020, 1144, 122096.
86. Silva, L. J.; Macedo, L.; Pereira, A. M.; Duarte, S.; Lino, C. M.; Pena, A., Ochratoxin A and Portuguese children: Urine biomonitoring, intake estimation and risk assessment. Food and Chemical Toxicology 2020, 135, 110883.
87. Ouhibi, S.; Vidal, A.; Martins, C.; Gali, R.; Hedhili, A.; De Saeger, S.; De Boevre, M., LC-MS/MS methodology for simultaneous determination of patulin and citrinin in urine and plasma applied to a pilot study in colorectal cancer patients. Food and Chemical Toxicology 2020, 136, 110994.
88. Arroyo-Manzanares, N.; Peñalver-Soler, R.; Campillo, N.; Viñas, P., Dispersive solid-phase extraction using magnetic carbon nanotube composite for the determination of emergent mycotoxins in urine samples. Toxins 2020, 12 (1), 51.
89. Liu, Z.; Zhao, X.; Wu, L.; Zhou, S.; Gong, Z.; Zhao, Y.; Wu, Y., Development of a Sensitive and Reliable UHPLC-MS/MS Method for the Determination of Multiple Urinary Biomarkers of Mycotoxin Exposure. Toxins 2020, 12 (3), 193.
90. Coronel, M. B.; Marin, S.; Tarragó, M.; Cano-Sancho, G.; Ramos, A.; Sanchis, V., Ochratoxin A and its metabolite ochratoxin alpha in urine and assessment of the exposure of inhabitants of Lleida, Spain. Food and chemical toxicology 2011, 49 (6), 1436-1442.
91. Qiao, X.; Li, G.; Zhang, J.; Du, J.; Yang, Y.; Yin, J.; Li, H.; Xie, J.; Jiang, Y.; Fang, X., Urinary analysis reveals high Alternaria mycotoxins exposure in the general population from Beijing, China. Journal of Environmental Sciences 2022, 118, 122-129.
92. Gerding, J.; Ali, N.; Schwartzbord, J.; Cramer, B.; Brown, D. L.; Degen, G. H.; Humpf, H.-U., A comparative study of the human urinary mycotoxin excretion patterns in Bangladesh, Germany, and Haiti using a rapid and sensitive LC-MS/MS approach. Mycotoxin research 2015, 31 (3), 127-136.
93. Ezekiel, C. N.; Warth, B.; Ogara, I. M.; Abia, W. A.; Ezekiel, V. C.; Atehnkeng, J.; Sulyok, M.; Turner, P. C.; Tayo, G. O.; Krska, R., Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers. Environment international 2014, 66, 138-145.
94. Solfrizzo, M.; Gambacorta, L.; Lattanzio, V. M.; Powers, S.; Visconti, A., Simultaneous LC–MS/MS determination of aflatoxin M 1, ochratoxin A, deoxynivalenol, de-epoxydeoxynivalenol, α and β-zearalenols and fumonisin B 1 in urine as a multi-biomarker method to assess exposure to mycotoxins. Analytical and bioanalytical chemistry 2011, 401 (9), 2831-2841.
95. Snyder, L. R.; Kirkland, J. J.; Glajch, J. L., Practical HPLC method development. John Wiley & Sons: 2012, Chapter 6.
96. Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B., Molecular beams of macroions. The Journal of chemical physics 1968, 49 (5), 2240-2249.
97. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M., Electrospray ionization for mass spectrometry of large biomolecules. Science 1989, 246 (4926), 64-71.
98. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M., Electrospray ionization–principles and practice. Mass Spectrometry Reviews 1990, 9 (1), 37-70.
99. Kebarle, P., A brief overview of the present status of the mechanisms involved in electrospray mass spectrometry. Journal of mass spectrometry 2000, 35 (7), 804-817.
100. Mora, J. F. d. l.; Van Berkel, G. J.; Enke, C. G.; Cole, R. B.; Martinez‐Sanchez, M.; Fenn, J. B., Electrochemical processes in electrospray ionization mass spectrometry. Journal of Mass Spectrometry 2000, 35 (8), 939-952.
101. Dass, C., Fundamentals of contemporary mass spectrometry. John Wiley & Sons: 2007; Vol. 16.
102. Duft, D.; Achtzehn, T.; Müller, R.; Huber, B. A.; Leisner, T., Rayleigh jets from levitated microdroplets. Nature 2003, 421 (6919), 128-128.
103. De Hoffmann, E.; Stroobant, V., Mass spectrometry: principles and applications. John Wiley & Sons: 2007.
104. Iribarne, J.; Thomson, B., On the evaporation of small ions from charged droplets. The Journal of chemical physics 1976, 64 (6), 2287-2294.
105. Fenn, J.; Rosell, J.; Nohmi, T.; Shen, S.; Banks Jr, F., Electrospray ion formation: desorption versus desertion. ACS Publications: 1996.
106. Konermann, L.; Ahadi, E.; Rodriguez, A. D.; Vahidi, S., Unraveling the mechanism of electrospray ionization. ACS Publications: 2013.
107. Matuszewski, B.; Constanzer, M.; Chavez-Eng, C., Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC− MS/MS. Analytical chemistry 2003, 75 (13), 3019-3030.
108. Agilent, Q-TOF LC/MS. www.creative-proteomics.com.
109. Vestal, M.; Juhasz, P.; Martin, S., Delayed extraction matrix‐assisted laser desorption time‐of‐flight mass spectrometry. Rapid Communications in Mass Spectrometry 1995, 9 (11), 1044-1050.
110. Mamyrin, B., Laser assisted reflectron time-of-flight mass spectrometry. International Journal of Mass Spectrometry and Ion Processes 1994, 131, 1-19.
111. O’Halloran, D.; Wolf, A.; Choset, H., Design of a high-impact survivable robot. Mechanism and machine theory 2005, 40 (12), 1345-1366.
112. Amiri, A.; Baghayeri, M.; Karimabadi, F.; Ghaemi, F.; Maleki, B., Graphene oxide/polydimethylsiloxane-coated stainless steel mesh for use in solid-phase extraction cartridges and extraction of polycyclic aromatic hydrocarbons. Microchimica Acta 2020, 187 (4), 1-8.
113. Tuanny Franco, L.; Mousavi Khaneghah, A.; In Lee, S. H.; Fernandes Oliveira, C. A., Biomonitoring of mycotoxin exposure using urinary biomarker approaches: a review. Toxin reviews 2019, 1-21.
114. McTaggart, M. P.; Price, C. P.; Pinnock, R. G.; Stevens, P. E.; Newall, R. G.; Lamb, E. J., The diagnostic accuracy of a urine albumin-creatinine ratio point-of-care test for detection of albuminuria in primary care. American journal of kidney diseases 2012, 60 (5), 787-794.
115. Toora, B.; Rajagopal, G., Measurement of creatinine by Jaffe's reaction-determination of concentration of sodium hydroxide required for maximum color development in standard, urine and protein free filtrate of serum. 2002.
116. Desharnais, B.; Camirand-Lemyre, F.; Mireault, P.; Skinner, C. D., Procedure for the selection and validation of a calibration model I—description and application. Journal of Analytical Toxicology 2017, 41 (4), 261-268.
117. Fjeldsted, J., Technical Overview.
118. Warth, B.; Sulyok, M.; Fruhmann, P.; Mikula, H.; Berthiller, F.; Schuhmacher, R.; Hametner, C.; Abia, W. A.; Adam, G.; Fröhlich, J., Development and validation of a rapid multi‐biomarker liquid chromatography/tandem mass spectrometry method to assess human exposure to mycotoxins. Rapid Communications in Mass Spectrometry 2012, 26 (13), 1533-1540.
119. Britannica The Editors of Encyclopaedia. "Urine". Encyclopedia Britannica, 15 Aug. https://www.britannica.com/science/urine (accessed 16 August 2021.).
120. Mazzachi, B. C.; Peake, M. J.; Ehrhardt, V., Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clinical laboratory 2000, 46 (1-2), 53-55.
121. Silva, A. S.; Brites, C.; Pouca, A. V.; Barbosa, J.; Freitas, A., UHPLC-ToF-MS method for determination of multi-mycotoxins in maize: Development and validation. Current Research in Food Science 2019, 1, 1-7.
122. Antignac, J.-P.; de Wasch, K.; Monteau, F.; De Brabander, H.; Andre, F.; Le Bizec, B., The ion suppression phenomenon in liquid chromatography–mass spectrometry and its consequences in the field of residue analysis. Analytica Chimica Acta 2005, 529 (1-2), 129-136.
123. Clarkson, M. R.; Brenner, B. M.; Magee, C., Pocket Companion to Brenner and Rector's the Kidney. Elsevier Health Sciences: 2010.
124. Zhang, Z.; Fan, Z.; Nie, D.; Zhao, Z.; Han, Z., Analysis of the carry-over of ochratoxin A from feed to milk, blood, urine, and different tissues of dairy cows based on the establishment of a reliable LC-MS/MS method. Molecules 2019, 24 (15), 2823.
125. Slobodchikova, I.; Vuckovic, D., Liquid chromatography–high resolution mass spectrometry method for monitoring of 17 mycotoxins in human plasma for exposure studies. Journal of Chromatography A 2018, 1548, 51-63.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.

Repository Staff Only: item control page

Downloads per month over past year

Research related to the current document (at the CORE website)
- Research related to the current document (at the CORE website)
Back to top Back to top