Formation of metal ion adducts in mass spectrometry, particularly in electrospray ionization liquid chromatography mass spectrometry (ESI-LC-MS), is a nightmare scenario for an analyst dealing with quantitative analysis. We have studied in detail the metal adduct formation and concluded that the use of fluorinated alkanoic acids along with formic acid and volatile ammonium salts was extremely useful in suppressing metal adduct formation in positive ion mode of ESI-LC-MS. The extremely high electronegativity of fluorine atom and unique electrostatic nature of C—F bond coupled with stereo-electronic interactions with neighboring bonds or lone pairs enables the polyfluorinated alkanoic acids in trapping highly electropositive ions (Na+, K+) thereby letting proton do its job efficiently. Addition of formic acid, trifluoroacetic acid, heptafluorobutyric acid and ammonium acetate was found to be extremely effective in controlling metal ion adducts and producing [M+H]+ ions almost exclusively resulting in significant increase in the sensitivity. This technique has been successfully used in our laboratory for the estimation of targeted and nontargeted analysis of pesticides, marine toxins, drugs and pharmaceuticals etc. in various matrices including environmental waters using liquid chromatography-time of flight mass spectrometer operated in all ion acquisition mode and triple quadruples (QQQ) in multiple reaction monitoring (MRM) mode.
Ammonium acetate, Electrospray ionization (ESI), Forensic sciences, Formic acid, Heptafluorobutyric acid (HFBA), Liquid chromatography-Mass spectrometry (LC-MS);, Metal ion adducts, Sensitivity, TOF
Becker, T. (2011). Methods for reducing adduct formation for mass spectrometry analysis. US patent, 7,888,127 B2.
Bester-Rogac, M. (2014). Ageing of Water or Dissolution of Glass: An Electrical Conductivity Study. Acta Chimica Slovenica, 61: 875-881.
Bohrer, D., Bortoluzzi, F., Nascimento P.V., Carvalho, M.L. and Ramirez, A.G. (2008) Silicate release from glass for pharmaceutical preparations. Int. J. Pharmaceutics 355: 174–183. doi:10.1016/j.ijpharm.2007.12.025.
Dowling, G. (2017). Analysis of Bitterness Compounds by Mass Spectrometry. In: Bitterness: Perception, Chemistry and Food Processing (Aliani, M. and Eskin, M.N.A., eds). Wiley Online Library. https://doi.org/10.1002/9781118590263.ch8.
Dunitz, J.D. and Taylor, R (1997). Organic Fluorine Hardly Ever Accepts Hydrogen Bonds. Chem. A Eur. Journal, 3: 89-98. https://doi.org/10.1002/chem.19970030115.
Erngren, I., Haglöf, J., Engskog, M.K.R., Nestor, M., Hedeland, M., Arvidsson, T. and Pettersson, C. (2019). Adduct formation in electrospray ionization-mass spectrometry with hydrophilic interaction liquid chromatography is strongly affected by the inorganic ion concentration of the samples. J. Chromatog. A, 1600: 174–182. doi: 10.1016/j.chroma.2019.04.049.
Escott, R.E.A. and Chandle, D.W. (1989). The Use of Ammonium Acetate as an Ion-Pairing Electrolyte for Ethoxylated Surfactant Analysis by Thermospray LC/MS. J. Chromatog. Sci., 27: 134–138, https://doi.org/10.1093/chromsci/27.3.134.
Gao, S., Zhan, Q., Li, J., Yang, Q., Li, X., Chen, W. and Sun, L. (2010)LC–MS/MS method for the simultaneous determination of ethyl gallate and its major metabolite in rat plasma. Biomed. Chromatog. 24: 472-78. https://doi.org/10.1002/bmc.1314.
Holcapek, M. and Byrdwell, W.C. (2017) Eds. Handbook of Advanced Chromatography/Mass Spectrometry Techniques. Academic Press London, UK
Hua, W., Lerardi, T., Lesslie, M., Hoffman, B.T. and Mulvana, D. (2014). Development and validation of a HILIC–MS/MS method for quantification of decitabine in human plasma by using lithium adduct detection. J. Chromatog. B, 969: 117–122. doi: 10.1016/j.jchromb.2014.08.012.
Jaikwang, P., Junkuy, A., Ratana Sapbamrer, R., Seesen, M., Khacha-ananda, S., Mueangkhiao, P. and Wunnapuk, K. (2020). A Dilute-and-Shoot LC–MS/MS Method for Urinary Glyphosate and AMPA. Chromatographia Pub Date: 2020-01-08, DOI: 10.1007/s10337-019-03853-3.
Konermann, L. (2017). Addressing a Common Misconception: Ammonium Acetate as Neutral pH “Buffer” for Native Electrospray Mass Spectrometry. J. Am. Soc. Mass Spectrom. 28(9): 1827-1835. DOI: 10.1021/jasms.8b0565
Kruve, A., Kaupmees, K., Liigand, J., Oss, M. and Leito, I. (2013). Sodium adduct formation efficiency in ESI source. J. Mass Spectrom., 48: 695-702. DOI 10.1002/jms.3218.
Kruve, A. and Kaupmees, K. (2017) Adduct Formation in ESI/MS by Mobile Phase Additives. J. Am. Soc. Mass Spectrom., 28: 887-894. https://doi.org/10.1007/s13361-017-1626-y.
Lambert, W. (2004). Pitfalls in LC-MS(-MS) Analysis. T + K, 71 (2): 64-68.
Leitner, A., Emmert, J., Boerner, K. and Lindner, W. (2007). Influence of Solvent: Additive Composition on Chromatographic Separation and Sodium Adduct Formation of Peptides in HPLC–ESI MS. Chromatographia, 65: 649-653. DOI: 10.1365/s10337-007-0219-50009-5893/07/06
Lemal, D.M. (2004) Perspective in fluorocarbon chemistry. J. Org. Chem. 69 (1): 1-11 https://doi.org/10.1021/jo0302556.
Marwah, A., Marwah, P., & Lardy, H. (2001). Liquid chromatography–electrospray ionization mass spectrometric analysis of corticosterone in rat plasma using selected ion monitoring. J. Chromatog. B: 757(2): 333–342. doi:10.1016/s0378-4347(01)00171-2.
Marwah, A., Marwah, P., Lardy, H.A. (2002). Analysis of ergosteroids VIII: Enhancement of signal response of natural steroidal compounds in liquid chromatographic-electrospray ionization mass spectrometric analysis by mobile phase additives. J. Chromatography A, 964: 137-51. DOI: 10.1016/s0021-9673(02)00650-7.
Mortier, K.A., Zhang, G.F., Van Peteghem, C.H. and Lambert, W.E (2004). Adduct formation in quantitative bioanalysis: Effect of ionization conditions on paclitaxel. J. Am. Soc. Mass Spectrom., 15: 585. DOI: 10.1016/j.jasms.2003.12.013.
Murtada, K., Andrés, F. de, Galván, I., Ríos, A., Zougagh, M. LC-MS determination of catecholamines and related metabolites in red deer urine and hair extracted using magnetic multi-walled carbon nanotube poly(styrene-co-divinylbenzene) composite, J. Chromatog. B (2019), doi: https://doi.org/10.1016/j.jchromb.2019.121878.
O'Hagan D (2008). "Understanding organofluorine chemistry. An introduction to the C–F bond". Chem Soc Rev. 37 (2): 308–19. doi:10.1039/b711844a. PMID 18197347.
Schugu, K. and McNair, H.M. (2002). Adduct formation in electrospray ionization. Part 1: Common acidic pharmaceuticals, J. Sep. Sci., 25:760-766. DOI: 10.1016/s0021-9673(02)01732-6.
Shou, W.Z. and Naidong, W. “Simple means to alleviate sensitivity loss by trifluoroacetic acid (TFA) mobile phases in the hydrophilic interaction chromatography-electrospray tandem mass spectrometric (HILIC-ESI/MS/MS) bioanalysis of basic compounds,” J. Chromatog. B, 825: 186–192. https://doi.org/10.1016/j.jchromb.2005.01.011–766.
Siuzdak, G. (2003). The Expanding role of mass spectrometry in Biotechnology. MCC Press, San Diego USA.
Thompson, M.J. (2018). Mass Spectrometry. Pan Stanford Publishing, Singapore.
Turkmen, Z., Kuloglu, M., Tekin, T., Mercan, S. and Bavunoglu, I. (2020). A GC-MS method for illegal stimulant drugs from serum by a multi-drug use sample in Turkey. J. Chem. Metrol. 13:2 (2019) 61-67. DOI: http://doi.org/10.25135/jcm.18.104.22.1689.
Vijlder, D.T, Valkenborg, D., Lemière, F., Romijn, E.P., Laukens K. and Cuyckens, F. (2018) A tutorial in small molecule identification via electrospray ionization-mass spectrometry: The practical art of structural elucidation. Mass Spectrom. Rev. 37(5):607-629. doi: 10.1002/mas.21551. Epub 2017 Nov 9.
Vogesser, M. and Seger, C. (2010) Pitfalls associated with the use of liquid chromatography-tandem mass spectrometry in the clinical laboratory. Clin Chem. 56(8):1234-44. doi: 10.1373/clinchem.2009.138602.
Yogi, K., Oshiro, N., Inafuku, Y., Hirama, M. and Yasumoto, T. (2011). Detailed LC-MS/MS Analysis of Ciguatoxins Revealing Distinct Regional and Species Characteristics in Fish and Causative Alga from the Pacific. Anal. Chem., 83: 8886-8891. doi.org/10.1021/ac200799j.
Yamin, T.S., Prihed, H., Madmon, M., Shifrovitch, A., Baratz, A. and Weissberg, A. (2019). Structural elucidation of phenidate analogues via the ESI-MS/MS spectra of their sodium adduct ions. Forensic Sci. Int. 306, 110044. doi:10.1016/j.forsciint.2019.110044.
Zhang, J-Z., Fischer, C.J. and Ortner, P.B. (1999) Laboratory glassware as a contaminant in silicate analysis of natural water samples. Wat. Res. 33: 2879-2883. https://doi.org/10.1016/S0043-1354(98)00508-9.
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