Research Article
BibTex RIS Cite

The Effect of A High-Resolution Accurate Mass Spectrometer On Simultaneous Multiple Mushroom Toxin Detection

Year 2020, Volume: 10 Issue: 4, 878 - 886, 15.10.2020
https://doi.org/10.17714/gumusfenbil.680816

Abstract

Amatoxins are deadly wild mushroom toxins that
cause severe poisoning in humans, from diarrhea to organ dysfunction. Mortality
can be as high as 80% if no specific treatment is applied. In this study,
separation and determination methods were developed for the simultaneous
determination of 7 toxins belonging to Amanita
phalloides
. After extraction and purification of Amanita phalloides (death cap) wild mushrooms, toxins were detected
using HPLC-ESI MS and exact mass with time of flight MS (TOF-MS) in positive
ionization mode. In addition, it was observed that the toxins of α- and
β-amanitine could be differentiated from each other thanks to HR-MS detection
in case of their close retention (Rt) in LC. The presence of two toxins at the
same retention point in the chromatogram
was detected by differentiating the molecular
ion mass (920.3514 DA) of the α-amanitine with the HR-MS (920.3696 DA). By
comparing both optimized methods with each other, faster and broad-spectrum
toxin identification was achieved compared to existing methods. In this study,
the rapid and accurate identification of seven toxins simultaneously with the
same method is of great importance. It will make important contributions to the
treatment process, especially by determining that poisoning is caused by wild
mushrooms.

Supporting Institution

TUBITAK BIDEB-2219 (International Post-Doctoral Research Fellowship Programme) and Ghent University ,Belgium

Project Number

1059B191401045

Thanks

She is also deeply indebted to Frederic Lynen, who supervised this study, and to Ghent University, Belgium, for granting access to all available infrastructure. Many thanks also to Ertuğrul Kaya from Düzce University who provided the dried Amanita phalloides.

References

  • Barceloux, D.G., 2008. Medical Toxicology of Natural Substances Part 2: FUNGAL TOXINS/ Mushrooms/Chapter 37:Amatoxin - Containing Mushrooms, 265-284pages.
  • Beavis, R.C., 1993. Chemical Mass of Carbon in Proteins. Analytical Chemistry 65 (4): 496–97. https://doi.org/10.1021/ac00052a030.
  • Burlingame, A. L., Whitney, J.O. ve Russell D.H.,1984. Mass Spectrometry. Analytical Chemistry. Vol. 56. https://doi.org/10.1021/ac00269a027.
  • Clarke, D.B., Lloyd, A.S. ve Robb, P., 2012. Application of Liquid Chromatography Coupled to Time-of-Flight Mass Spectrometry Separation for Rapid Assessment of Toxins in Amanita Mushrooms. Analytical Methods 4 (5): 1298. https://doi.org/10.1039/c2ay05575a.
  • Damme, T.V., Blancquaert, D., Couturon, P., V.D.S., Dominique, Sandra, P. ve Lynen, F., 2014. Wounding Stress Causes Rapid Increase in Concentration of the Naturally Occurring 2′,3′-Isomers of Cyclic Guanosine- and Cyclic Adenosine Monophosphate (CGMP and CAMP) in Plant Tissues. Phytochemistry. https://doi.org/10.1016/j.phytochem.2014.03.013.
  • Defendenti, C., Bonacina, E., Mauroni, M. ve Gelosa, L., 1998. Validation of a High Performance Liquid Chromatographic Method for Alpha Amanitin Determination in Urine. Forensic Science International 92 (1): 59–68. https://doi.org/10.1016/S0379-0738(98)00006-1.
  • Garcia, J., Vera, M.C., Baptista, P., Bastos, M.de L., ve Carvalho, F., 2015. Quantification of Alpha-Amanitin in Biological Samples by HPLC Using Simultaneous UV- Diode Array and Electrochemical Detection. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 997: 85–95. https://doi.org/10.1016/j.jchromb.2015.06.001.
  • Gicquel, T., Lepage, S., Fradin, M., Tribut, O., Duretz, B. ve Morel, I., 2014. Amatoxins (Amanitin) and Phallotoxin (Phalloidin) Analyses in Urines Using High-Resolution Accurate Mass LC-MS Technology. Journal of Analytical Toxicology 38 (6): 335–40. https://doi.org/10.1093/jat/bku035.
  • Gonmori, K., Fujita, H., Yokoyama, K., Watanabe, K. ve Suzuki, O., 2011. Mushroom Toxins: A Forensic Toxicological Review. Forensic Toxicology 29 (2): 85–94. https://doi.org/10.1007/s11419-011-0115-4.
  • Gonmori, K., Minakata, K., Suzuki, M., Yamagishi, I., Nozawa, H., Hasegawa, K., Wurita, A., Watanabe, K. ve Suzuki, O., 2012. MALDI-TOF Mass Spectrometric Analysis of α-Amanitin, β-Amanitin, and Phalloidin in Urine. Forensic Toxicology 30 (2): 179–84. https://doi.org/10.1007/s11419-012-0145-6.
  • ICH. 1996. Guidance for Industry: Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonisation of Technical Requirements for Registration Tripartite Guideline. https://doi.org/62 FR 27464.
  • Kaya, E., Karahan, S., Bayram, R., Yaykasli K.O., Colakoglu, S. ve Saritas, A., 2015. Amatoxin and Phallotoxin Concentration in Amanita Phalloides Spores and Tissues. Toxicology and Industrial Health 31 (12): 1172–77. https://doi.org/10.1177/0748233713491809.
  • Kaya, E., Yilmaz, I., Sinirlioglu, Z.A., Karahan, S., Bayram, R., Yaykasli, K.O., Colakoglu, S., Saritas, A. ve Severoglu, Z., 2013. Amanitin and Phallotoxin Concentration in Amanita Phalloides Var. Alba Mushroom. Toxicon 76 (December): 225–33. https://doi.org/10.1016/j.toxicon.2013.10.008.
  • Li, W., Gu, Z., Yang, Y., Zhou, S., Liu, Y. ve Zhang J., 2014. Non-Volatile Taste Components of Several Cultivated Mushrooms. Food Chemistry. https://doi.org/10.1016/j.foodchem.2013.08.006.
  • Maurer, H.H., Kraemer, T., Ledvinka, O., Schmitt, C.J. ve Weber, A.A., 1997. Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) in Toxicological Analysis. Studies on the Detection of Clobenzorex and Its Metabolites within a Systematic Toxicological Analysis Procedure by GC-MS and by immunoassay and studies on the detection of α- and β-amanitin in urine by atmospheric pressure ionization electrospray LC-MS. Journal of Chromatography. B, Biomedical Sciences and Applications 689 (1): 81–89.
  • Maurer, H.H., Schmitt, C.J., Weber, A.A. ve Kraemer, T., 2000. Validated Electrospray Liquid Chromatographic–Mass Spectrometric Assay for the Determination of the Mushroom Toxins a- and b-Amanitin in Urine after Immunoaffinity Extraction. Journal of Chromatography B 748: 125–35.
  • Mcknight, T.A, Mcknight, K. B. ve Skeels, M.C., 2015. Source Mycologia, No July August, and C Skeels.. Amatoxin and Phallotoxin Concentration in Amanita Bisporigera Spores Amatoxin Bispotigera. Mycological Society of America 102 (4): 763–65.
  • Nicolescu, T.O., 2017. Interpretation of Mass Spectra. In Mass Spectrometry. InTech. https://doi.org/10.5772/intechopen.68595.
  • Robinson-Fuentes, V. A., Jaime-Sânche , J. L., Garcia-Aguilar, L., Gômez-Peralta, M., Vâzquez-Garciduenas, M.S. ve Vazquez-Marrufo, G., 2008. Determination of Alpha- and Beta-Amanitin in Clinical Urine Samples by Capillary Zone Electrophoresis. Journal of Pharmaceutical and Biomedical Analysis 47 (4–5): 913–17.
  • Shintani, H., 2014. Toxic Compounds Analysis With High Performance Liquid Chromatography Detected By Electro Chemical Detector (Ecd). Int J Clin Pharmacol Toxicol. 3 (3): 121–27. https://doi.org/dx.doi.org/10.19070/2167-910X-1400022.
  • Unluoglu, I.ve Tayfur, M., 2003. Mantar Zehirlenmesi. European Journal of Emergency Medicine 10 (October): 23–26. https://doi.org/10.1097/01.mej.0000057022.75699.93.
  • Vargas, N., Bernal, A., Sarria,V., Franco-Molano, A. ve Restrepo, S., 2011. Amatoxin and Phallotoxin Composition in Species of the Genus Amanita in Colombia: A Taxonomic Perspective. Toxicon 58 (6–7): 583–90. https://doi.org/10.1016/j.toxicon.2011.09.005.
  • Ventura, S., Ruiz, C., Durán, E., Mosquera, M., Bandrés, F., Campos, F., Castanyer, B. et al., 2015. Amanitinas. Revista Del Laboratorio Clínico 8 (3): 109–26. https://doi.org/10.1016/j.labcli.2015.05.001.
  • Vetter, J., 1998. Toxins of Amanita Phalloides. Toxicon 36 (1): 13–24. https://doi.org/10.1016/S0041-0101(97)00074-3.
  • Wharf, C., ve United Kingdom. 2012. Guideline on Bioanalytical Method Validation Guideline on Bioanalytical Method Validation Table of Contents. 44 (July 2011): 1–23.
  • Yilmaz, I., Kaya, E., Sinirlioglu, Z.A., Bayram, R., Surmen, M.G. ve Colakoglu, S., 2014. Clinical Importance of Toxin Concentration in Amanita Verna Mushroom. Toxicon 87: 68–75. https://doi.org/10.1016/j.toxicon.2014.05.019.

Yüksek Çözünürlüklü Kütle Spektrometrenin Eşzamanlı Çoklu Mantar Toksin Tayinleri Üzerindeki Etkisi

Year 2020, Volume: 10 Issue: 4, 878 - 886, 15.10.2020
https://doi.org/10.17714/gumusfenbil.680816

Abstract

Amatoksinler, insanlarda
ishalden organ işlev bozukluğuna kadar ciddi zehirlenmelere neden olan ölümcül
yabani mantar toksinleridir. Spesifik bir tedavi uygulanmazsa mortalite %80
kadar yüksek olabilir. Bu çalışmada Amanita phalloides' e ait 7 tane toksinin
eş zamanda belirlenmesi için ayırma ve tayin yöntemleri geliştirildi. Amanita
phalloides (ölüm kapağı) yabani mantarının ekstraksiyonu ve saflaştırılmasının
ardından toksinler, HPLC-ESI MS ve LC-doğru kütle uçuş zamanlı MS (TOF-MS) pozitif
iyonizasyon modu kullanılarak tespit edildi. Ayrıca α- ve β-amanitin toksinlerinin
LC'de birbirlerine çok yakın alıkonmaları (Rt) durumunda HR-MS özellikteki
dedeksiyon sayesinde birbirlerinden ayırt edilmesinin mümkün olduğu görüldü. Kromatogramda
aynı alıkonma noktasında iki toksin varlığı HR-MS sayesinde α-amanitinin C13
izotop kütlesi (920.3696 DA) ile β-amanitinin moleküler iyon kütlesinin (
920.3514 DA) farklandırılması
yapılarak tespit edildi. Optimize edilmiş her iki yöntem birbirleriyle
karşılaştırılarak mevcut yöntemlere göre daha hızlı ve geniş spektrumlu toksin
tanımlaması geçekleştirildi. Bu çalışmada aynı yöntem ile eş zamanda yedi adet
toksinin hızlı ve doğru tanımlanması büyük önem taşımaktadır. Özellikle zehirlenmenin
yabani mantardan kaynaklı olduğunun belirlenmesi ile tedavi sürecinde önemli
katkılar sağlayacaktır.

Project Number

1059B191401045

References

  • Barceloux, D.G., 2008. Medical Toxicology of Natural Substances Part 2: FUNGAL TOXINS/ Mushrooms/Chapter 37:Amatoxin - Containing Mushrooms, 265-284pages.
  • Beavis, R.C., 1993. Chemical Mass of Carbon in Proteins. Analytical Chemistry 65 (4): 496–97. https://doi.org/10.1021/ac00052a030.
  • Burlingame, A. L., Whitney, J.O. ve Russell D.H.,1984. Mass Spectrometry. Analytical Chemistry. Vol. 56. https://doi.org/10.1021/ac00269a027.
  • Clarke, D.B., Lloyd, A.S. ve Robb, P., 2012. Application of Liquid Chromatography Coupled to Time-of-Flight Mass Spectrometry Separation for Rapid Assessment of Toxins in Amanita Mushrooms. Analytical Methods 4 (5): 1298. https://doi.org/10.1039/c2ay05575a.
  • Damme, T.V., Blancquaert, D., Couturon, P., V.D.S., Dominique, Sandra, P. ve Lynen, F., 2014. Wounding Stress Causes Rapid Increase in Concentration of the Naturally Occurring 2′,3′-Isomers of Cyclic Guanosine- and Cyclic Adenosine Monophosphate (CGMP and CAMP) in Plant Tissues. Phytochemistry. https://doi.org/10.1016/j.phytochem.2014.03.013.
  • Defendenti, C., Bonacina, E., Mauroni, M. ve Gelosa, L., 1998. Validation of a High Performance Liquid Chromatographic Method for Alpha Amanitin Determination in Urine. Forensic Science International 92 (1): 59–68. https://doi.org/10.1016/S0379-0738(98)00006-1.
  • Garcia, J., Vera, M.C., Baptista, P., Bastos, M.de L., ve Carvalho, F., 2015. Quantification of Alpha-Amanitin in Biological Samples by HPLC Using Simultaneous UV- Diode Array and Electrochemical Detection. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 997: 85–95. https://doi.org/10.1016/j.jchromb.2015.06.001.
  • Gicquel, T., Lepage, S., Fradin, M., Tribut, O., Duretz, B. ve Morel, I., 2014. Amatoxins (Amanitin) and Phallotoxin (Phalloidin) Analyses in Urines Using High-Resolution Accurate Mass LC-MS Technology. Journal of Analytical Toxicology 38 (6): 335–40. https://doi.org/10.1093/jat/bku035.
  • Gonmori, K., Fujita, H., Yokoyama, K., Watanabe, K. ve Suzuki, O., 2011. Mushroom Toxins: A Forensic Toxicological Review. Forensic Toxicology 29 (2): 85–94. https://doi.org/10.1007/s11419-011-0115-4.
  • Gonmori, K., Minakata, K., Suzuki, M., Yamagishi, I., Nozawa, H., Hasegawa, K., Wurita, A., Watanabe, K. ve Suzuki, O., 2012. MALDI-TOF Mass Spectrometric Analysis of α-Amanitin, β-Amanitin, and Phalloidin in Urine. Forensic Toxicology 30 (2): 179–84. https://doi.org/10.1007/s11419-012-0145-6.
  • ICH. 1996. Guidance for Industry: Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonisation of Technical Requirements for Registration Tripartite Guideline. https://doi.org/62 FR 27464.
  • Kaya, E., Karahan, S., Bayram, R., Yaykasli K.O., Colakoglu, S. ve Saritas, A., 2015. Amatoxin and Phallotoxin Concentration in Amanita Phalloides Spores and Tissues. Toxicology and Industrial Health 31 (12): 1172–77. https://doi.org/10.1177/0748233713491809.
  • Kaya, E., Yilmaz, I., Sinirlioglu, Z.A., Karahan, S., Bayram, R., Yaykasli, K.O., Colakoglu, S., Saritas, A. ve Severoglu, Z., 2013. Amanitin and Phallotoxin Concentration in Amanita Phalloides Var. Alba Mushroom. Toxicon 76 (December): 225–33. https://doi.org/10.1016/j.toxicon.2013.10.008.
  • Li, W., Gu, Z., Yang, Y., Zhou, S., Liu, Y. ve Zhang J., 2014. Non-Volatile Taste Components of Several Cultivated Mushrooms. Food Chemistry. https://doi.org/10.1016/j.foodchem.2013.08.006.
  • Maurer, H.H., Kraemer, T., Ledvinka, O., Schmitt, C.J. ve Weber, A.A., 1997. Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) in Toxicological Analysis. Studies on the Detection of Clobenzorex and Its Metabolites within a Systematic Toxicological Analysis Procedure by GC-MS and by immunoassay and studies on the detection of α- and β-amanitin in urine by atmospheric pressure ionization electrospray LC-MS. Journal of Chromatography. B, Biomedical Sciences and Applications 689 (1): 81–89.
  • Maurer, H.H., Schmitt, C.J., Weber, A.A. ve Kraemer, T., 2000. Validated Electrospray Liquid Chromatographic–Mass Spectrometric Assay for the Determination of the Mushroom Toxins a- and b-Amanitin in Urine after Immunoaffinity Extraction. Journal of Chromatography B 748: 125–35.
  • Mcknight, T.A, Mcknight, K. B. ve Skeels, M.C., 2015. Source Mycologia, No July August, and C Skeels.. Amatoxin and Phallotoxin Concentration in Amanita Bisporigera Spores Amatoxin Bispotigera. Mycological Society of America 102 (4): 763–65.
  • Nicolescu, T.O., 2017. Interpretation of Mass Spectra. In Mass Spectrometry. InTech. https://doi.org/10.5772/intechopen.68595.
  • Robinson-Fuentes, V. A., Jaime-Sânche , J. L., Garcia-Aguilar, L., Gômez-Peralta, M., Vâzquez-Garciduenas, M.S. ve Vazquez-Marrufo, G., 2008. Determination of Alpha- and Beta-Amanitin in Clinical Urine Samples by Capillary Zone Electrophoresis. Journal of Pharmaceutical and Biomedical Analysis 47 (4–5): 913–17.
  • Shintani, H., 2014. Toxic Compounds Analysis With High Performance Liquid Chromatography Detected By Electro Chemical Detector (Ecd). Int J Clin Pharmacol Toxicol. 3 (3): 121–27. https://doi.org/dx.doi.org/10.19070/2167-910X-1400022.
  • Unluoglu, I.ve Tayfur, M., 2003. Mantar Zehirlenmesi. European Journal of Emergency Medicine 10 (October): 23–26. https://doi.org/10.1097/01.mej.0000057022.75699.93.
  • Vargas, N., Bernal, A., Sarria,V., Franco-Molano, A. ve Restrepo, S., 2011. Amatoxin and Phallotoxin Composition in Species of the Genus Amanita in Colombia: A Taxonomic Perspective. Toxicon 58 (6–7): 583–90. https://doi.org/10.1016/j.toxicon.2011.09.005.
  • Ventura, S., Ruiz, C., Durán, E., Mosquera, M., Bandrés, F., Campos, F., Castanyer, B. et al., 2015. Amanitinas. Revista Del Laboratorio Clínico 8 (3): 109–26. https://doi.org/10.1016/j.labcli.2015.05.001.
  • Vetter, J., 1998. Toxins of Amanita Phalloides. Toxicon 36 (1): 13–24. https://doi.org/10.1016/S0041-0101(97)00074-3.
  • Wharf, C., ve United Kingdom. 2012. Guideline on Bioanalytical Method Validation Guideline on Bioanalytical Method Validation Table of Contents. 44 (July 2011): 1–23.
  • Yilmaz, I., Kaya, E., Sinirlioglu, Z.A., Bayram, R., Surmen, M.G. ve Colakoglu, S., 2014. Clinical Importance of Toxin Concentration in Amanita Verna Mushroom. Toxicon 87: 68–75. https://doi.org/10.1016/j.toxicon.2014.05.019.
There are 26 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Yasemin Numanoğlu Çevik 0000-0001-5818-7881

Project Number 1059B191401045
Publication Date October 15, 2020
Submission Date January 29, 2020
Acceptance Date July 2, 2020
Published in Issue Year 2020 Volume: 10 Issue: 4

Cite

APA Numanoğlu Çevik, Y. (2020). Yüksek Çözünürlüklü Kütle Spektrometrenin Eşzamanlı Çoklu Mantar Toksin Tayinleri Üzerindeki Etkisi. Gümüşhane Üniversitesi Fen Bilimleri Dergisi, 10(4), 878-886. https://doi.org/10.17714/gumusfenbil.680816