Abstract
Where does flow injection analysis mass spectrometry (FIA-MS) stand relative to ambient mass spectrometry (MS) and chromatography-MS? Improvements in FIA-MS methods have resulted in fast-expanding uses of this technique. Key advantages of FIA-MS over chromatography-MS are fast analysis (typical run time <60 s) and method simplicity, and FIA-MS offers high-throughput without compromising sensitivity, precision and accuracy as much as ambient MS techniques. Consequently, FIA-MS is increasingly becoming recognized as a suitable technique for applications where quantitative screening of chemicals needs to be performed rapidly and reliably. The FIA-MS methods discussed herein have demonstrated quantitation of diverse analytes, including pharmaceuticals, pesticides, environmental contaminants, and endogenous compounds, at levels ranging from parts-per-billion (ppb) to parts-per-million (ppm) in very complex matrices (such as blood, urine, and a variety of foods of plant and animal origin), allowing successful applications of the technique in clinical diagnostics, metabolomics, environmental sciences, toxicology, and detection of adulterated/counterfeited goods. The recent boom in applications of FIA-MS for high-throughput quantitative analysis has been driven in part by (1) the continuous improvements in sensitivity and selectivity of MS instrumentation, (2) the introduction of novel sample preparation procedures compatible with standalone mass spectrometric analysis such as salting out assisted liquid–liquid extraction (SALLE) with volatile solutes and NH4 + QuEChERS, and (3) the need to improve efficiency of laboratories to satisfy increasing analytical demand while lowering operational cost. The advantages and drawbacks of quantitative analysis by FIA-MS are discussed in comparison to chromatography-MS and ambient MS (e.g., DESI, LAESI, DART). Generally, FIA-MS sits ‘in the middle’ between ambient MS and chromatography-MS, offering a balance between analytical capability and sample analysis throughput suitable for broad applications in life sciences, agricultural chemistry, consumer safety, and beyond.
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Abbreviations
- APCI:
-
Atmospheric pressure chemical ionization
- API:
-
Active pharmaceutical ingredient
- ASAP:
-
Atmospheric solids analysis probe
- DART:
-
Direct analysis in real time
- DESI:
-
Desorption electrospray ionization
- ESI:
-
Electrospray ionization
- FIA:
-
Flow injection analysis
- FI-MS:
-
Flow injection mass spectrometry
- GC-MS:
-
Gas chromatography-mass spectrometry
- GC-MS/MS:
-
Gas chromatography-mass spectrometry/mass spectrometry
- GPC:
-
Gel permeation chromatography
- HPLC-MS:
-
High performance liquid chromatography-mass spectrometry
- HPLC-MS/MS:
-
High performance liquid chromatography-mass spectrometry/mass spectrometry
- LAESI:
-
Laser ablation electrospray ionization
- LOD:
-
Limit of detection
- LOQ:
-
Limit of quantitation
- MALDI:
-
Matrix-assisted laser desorption ionization
- MS:
-
Mass spectrometry (MS is used in this paper as a general abbreviation for mass spectrometry using all types of mass analyzers, including single-stage mass spectrometry, tandem mass spectrometry, etc.)
- MS/MS:
-
Mass spectrometry/mass spectrometry or tandem mass spectrometry (MS/MS is used in this paper specifically for two stages of mass analysis)
- QuEChERS:
-
Quick easy cheap effective rugged and safe (a sample preparation method)
- SALLE:
-
Salting out assisted liquid-liquid extraction
- SPE:
-
Solid-phase extraction
- Standalone MS:
-
Mass spectrometry techniques without chromatography, including DESI-MS, DART-MS, FIA-MS, LAESI-MS, MALDI-MS, etc.
References
Thomson JJ (1913) Positive rays of electricity. Nature 91:362
Aston FW (1920) Isotopes and atomic weights. Nature 105:617–619
Grayson MA (2002) Measuring Mass: From Positive Rays to Proteins. Chemical Heritage Press, Philadelphia
McLafferty FW, Gohlke RS (1993) Early gas chromatography/mass spectrometry. J Am Soc Mass Spectrom 4:367–371
Horning EC, Horning MG, Carroll DI, Dzidic I, Stillwell RN (1973) New picogram detection system based on a mass spectrometer with an external ionization source at atmospheric pressure. Anal Chem 45:936–943
Thomson B (2012) Driving high sensitivity in biomolecular MS. Genet Eng Biotechn 32:20
Bui HA, Cooks RG (1998) Windows version of the ion trap simulation program ITSIM: a powerful heuristic and predictive tool in ion trap mass spectrometry. J Mass Spectrom 33:297–304
Van Oudenhove L, Devreese B (2013) A review on recent developments in mass spectrometry instrumentation and quantitative tools advancing bacterial proteomics. Appl Microbiol Biotechnol 97:4749–4762
Anastassiades M, Lehotay SJ, Stajnbaher D, Schenck FJ (2003) Fast and easy multiresidue method employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in produce. J AOAC Int 86:412–431
Lehotay SJ, De Kok A, Hiemstra M, Van Bodegraven P (2005) Validation of a fast and easy method for the determination of residues from 229 pesticides in fruits and vegetables using gas and liquid chromatography and mass spectrometric detection. J AOAC Int 88:595–614
Bruzzoniti MC, Checchini L, De Carlo RM, Orlandini S, Rivoira L, Del Bubba M (2015) QuEChERS sample preparation for the determination of pesticides and other organic residues in environmental matrices: a critical review. Anal Bioanal Chem 406:4089–4116
Wu H, Zhang J, Norem K, El-Shourbagy TA (2008) Simultaneous determination of a hydrophobic drug candidate and its metabolite in human plasma with salting-out assisted liquid/liquid extraction using a mass spectrometry friendly salt. J Pharm Biomed Anal 48:1243–1248
Zhang J, Rodila R, Gage E, Hautman M, Fan L, King LL, Wu H, El-Shourbagy TA (2010) High-throughput salting-out assisted liquid/liquid extraction with acetonitrile for the simultaneous determination of simvastatin and simvastatin acid in human plasma with liquid chromatography. Anal Chim Acta 661:167–172
Yang Y, Xu Q, Zhou L, Zhong D, Chen X (2015) High-throughput salting-out-assisted liquid-liquid extraction for the simultaneous determination of atorvastatin, ortho-hydroxyatorvastatin, and para-hydroxyatorvastatin in human plasma using ultrafast liquid chromatography with tandem mass spectrometry. J Sep Sci 38:1026–1034
Mol HGJ, Plaza-Bolaños P, Zomer P, de Rijk TC, Stolker AAM, Mulder PPJ (2008) Toward a generic extraction method for simultaneous determination of pesticides, mycotoxins, plant toxins, and veterinary drugs in feed and food matrixes. Anal Chem 80:9450–9459
Stahnke H, Kittlaus S, Kempe G, Alder L (2012) Reduction of matrix effects in liquid chromatography-electrospray ionization-mass spectrometry by dilution of the sample extracts: How much dilution is needed? Anal Chem 84:1474–1482
Deventer K, Pozo OJ, Verstraete AG, Van Eenoo P (2014) Dilute-and-shoot-liquid chromatography-mass spectrometry for urine analysis in doping control and analytical toxicology. TrAC-Trends Anal Chem 55:1–13
Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473
Cody RB, Laramée JA, Durst HD (2005) Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal Chem 77:2297–2302
McEwen CN, McKay RG, Larsen BS (2005) Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments. Anal Chem 77:7826–7831
Monge ME, Fernandez FM (2015) An introduction to ambient ionization mass spectrometry. New Dev Mass Spectrom 2:1–22
Espy RD, Wleklinski M, Yan X, Cooks RG (2014) Beyond the flask: reactions on the fly in ambient mass spectrometry. TrAC-Trends Anal Chem 57:135–146
Schug K (2013) The LCGC blog: flow injection analysis can be used to create temporal compositional analyte gradients for mass spectrometry-based quantitative analysis. Available at: http://www.chromatographyonline.com. Accessed 30 Septembrer 2015
Niessen WMA (1998) Advances in instrumentation in liquid chromatography-mass spectrometry and related liquid-introduction techniques. J Chromatogr A 794:407–435
Goto T, Ito Y, Oka H, Saito I, Matsumoto H, Nakazawa H (2003) Simple and rapid determination of N-methylcarbamate pesticides in citrus fruit by electrospray ionization tandem mass spectrometry. Anal Chim Acta 487:201–209
Ito Y, Goto T, Oka H, Matsumoto H, Miyazaki Y (2003) Simple and rapid determination of thiabendazole, imazalil, and o-phenylphenol in citrus fruit using flow-injection electrospray ionization tandem mass spectrometry. J Agric Food Chem 51:861–866
Geerdink RB, Kienhuis PGM, Brinkman UAT (1993) Fast screening method for eight phenoxyacid herbicides and bentazone in water optimization procedures for flow-injection analysis-thermospray tandem mass spectrometry. J Chromatogr A 647:329–339
Santos IC, Waybright VB, Fan H, Ramirez S, Mesquita RBR, Rangel AOSS, Fryčák P, Schug KA (2015) Determination of noncovalent binding using a continuous stirred tank reactor as a flow injection device coupled to electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 26:1204–1212
Schug KA, Serrano C, Fryčák P (2010) Controlled band dispersion for quantitative binding determination and analysis with electrospray ionization-mass spectrometry. Mass Spectrom Rev 29:806–829
Nanita SC (2013) Quantitative mass spectrometry independence from matrix effects and detector saturation achieved by flow injection analysis with real-time infinite dilution. Anal Chem 85:11866–11875
Nanita SC, Pentz AM, Bramble FQ (2009) High-throughput pesticide residue quantitative analysis achieved by tandem mass spectrometry with automated flow injection. Anal Chem 81:3134–3142
Mol HGJ, van Dam RCJ (2014) Rapid detection of pesticides not amenable to multi-residue methods by flow injection-tandem mass spectrometry. Anal Bioanal Chem 406:6817–6825
Nanita SC (2011) High-throughput chemical residue analysis by fast extraction and dilution flow injection mass spectrometry. Analyst 136:285–287
Nanita SC, Stry JJ, Pentz AM, McClory JP, May JH (2011) Fast extraction and dilution flow injection mass spectrometry method for quantitative chemical residue screening in food. J Agric Food Chem 59:7557–7568
Kostiainen R, Kauppila TJ (2009) Effect of eluent on the ionization process in liquid chromatography-mass spectrometry. J Chromatogr A 1216:685–699
Mallet CR, Lu Z, Mazzeo JR (2004) A study of ion suppression effects in electrospray ionization from mobile phase additives and solid phase extracts. Rapid Commun Mass Spectrom 18:49–58
Song F, El-Demerdash A, Lee SJ, Smith RE (2012) Fast screening of lovastatin in red yeast rice products by flow injection tandem mass spectrometry. J Pharm Biomed 57:76–81
Song F, El-Demerdash A, Lee SJ (2012) Screening for multiple phosphodiesterase type 5 inhibitor drugs in dietary supplement materials by flow injection mass spectrometry and their quantification by liquid chromatography tandem mass spectrometry. J Pharm Biomed 70:40–46
Song F, Monroe D, El-Demerdash A, Palmer C (2014) Screening for multiple weight loss and related drugs in dietary supplement materials by flow injection tandem mass spectrometry and their confirmation by liquid chromatography tandem mass spectrometry. J Pharm Biomed 88:136–143
Lehotay SJ, Lightfield AR, Schneider MJ, Winkler PC (2014) High throughput analysis using guard-column UHPLC-DMS-MS/MS to screen veterinary drug residues in animal tissues. Proceedings of the 62nd ASMS Conference on Mass Spectrometry and Allied Topics (ThOC am 9:50), Baltimore, Maryland, USA
García-Reyes JF, Jackson AU, Molina-Díaz A, Cooks RG (2009) Desorption electrospray ionization mass spectrometry for trace analysis of agrochemicals in food. Anal Chem 81:820–829
Nanita SC, Padivitage NLT (2013) Ammonium chloride salting out extraction/cleanup for trace-level quantitative analysis in food and biological matrices by flow injection tandem mass spectrometry. Anal Chim Acta 768:1–11
Nanita SC, Kaldon LG (2015) Ammonium salting out extraction with analyte preconcentration for sub-part per billion quantitative analysis in surface, ground and drinking water by flow injection tandem mass spectrometry. Anal Methods 7:2300–2312
Han L, Sapozhnikova Y, Lehotay SJ (2014) Streamlined sample cleanup using combined dispersive solid-phase extraction and in-vial filtration for analysis of pesticides and environmental pollutants in shrimp. Anal Chim Acta 827:40–46
Gonzalez-Curbelo MA, Lehotay SJ, Borges JH, Rodriguez-Delgado MA (2014) Use of ammonium formate in QuEChERS for high-throughput analysis of pesticides in food by fast, low-pressure gas chromatography and liquid chromatography tandem mass spectrometry. J Chromatogr A 1358:75–84
Johnson DW (2010) An acid hydrolysis method for quantification of plasma free and total carnitine by flow injection tandem mass spectrometry. Clin Biochem 43:1362–1367
Sander M, Becker S, Thiery J, Ceglarek U (2015) Simultaneous identification and quantitation of triacyglycerol species in human plasma by flow-injection electrospray ionization tandem mass spectrometry. Chromatographia 78:435–443
Niesser M, Koletzko B, Peisser W (2012) Determination of creatinine in human urine with flow injection tandem mass spectrometry. Ann Nutr Metab 61:314–321
Jaffé M (1886) Ueber den niederschlag, welchen pikrinsäure im normalen harn erzeugt, und über eine neue reaction des kreatinins. Z Physiol Chem 10:391–400
Wu L, Vogt FG, Liu DQ (2013) Flow-injection MS/MS for gas-phase chiral recognition and enantiomeric quantitation of a novel boron-containing antibiotic (GSK2251052A) by the mass spectrometric kinetic method. Anal Chem 85:4869–4874
Wu L, Meurer EC, Cooks RG (2004) Chiral morphing and enantiomeric quantification in mixtures by mass spectrometry. Anal Chem 76:663–671
Young BL, Cooks RG, Madden MC, Bair M, Jia J, Aubry AF, Miller SA (2007) Chiral purity assay for Flindokalner using tandem mass spectrometry: method development, validation, and benchmarking. J Pharm Biomed 43:1602–1608
Miguel-Framil M, Moreda- Piñeiro A, Bermejo-Barrera P, Cocho JA, Yabernero MJ, Bermejo AM (2011) Electrospray ionization tandem mass spectrometry for the simultaneous determination of opiates and cocaine in human hair. Anal Chim Acta 704:123–132
Michel D, Gaunt MC, Arnason T, El-Aneed A (2015) Development and validation of fast and simple flow injection analysis-tandem mass spectrometry (FIA-MS/MS) for the determination of metformin in dog serum. J Pharm Biomed 107:229–235
John H, Eddleston M, Clutton RE, Worek F, Thiermann H (2010) Simultaneous quantification of the organophosphorus pesticides dimethoate and omethoate in porcine plasma and urine by LC-ESI-MS/MS and flow-injection-ESI-MS/MS. J Chromatogr B 878:1234–1245
Oellig C, Schwack W (2014) Planar solid phase extraction clean-up and microliter-flow injection analysis-time-of-flight mass spectrometry for multi-residue screening of pesticides in food. J Chromatogr A 1351:1–11
Bhandari D, Kertesz V, Van Berkel GJ (2013) Rapid quantitation of ascorbic and folic acids in SRM 3280 multivitamin/multi-element tablets using flow-injection tandem mass spectrometry. Rapid Commun Mass Spectrom 27:163–168
Bhandari D, Van Berkel GJ (2012) Evaluation of flow-injection tandem mass spectrometry for rapid and high-throughput quantitative determination of b vitamins in nutritional supplements. J Agric Food Chem 60:8356–8362
Sun J, Chen P (2011) A flow-injection mass spectrometry fingerprinting method for authentication and quality assessment of Scutellaria lateriflora-based dietary supplements. Anal Bioanal Chem 401:1581–1588
Hostetler DM, Dwivedi P, Green MD, Fernandez F (2012) High throughput quantitation of artesunate and its degradation products by flow injection gradient ratio standard addition mass spectrometry (FI-GRSA-MS). Anal Methods 4:3392–3398
Culzoni MJ, Dwivedi P, Green MD, Newton PN, Fernandez F (2014) Ambient mass spectrometry technologies for the detection of falsified drugs. Med Chem Commun 5:9–19
Tabernero P, Fernandez FM, Green M, Guerin PJ, Newton PN (2014) Mind the gaps—the epidemiology of poor-quality anti-malarials in the malarious world—analysis of the Worldwide Antimalarial Resistance Network database. Malar J 13:139
Gonzalez-Dominguez R, Garcia-Barrera T, Gomez-Ariza JL (2015) Application of a novel metabolomic approach based on atmospheric pressure photoionization mass spectrometry using flow injection analysis for the study of Alzheimer’s disease. Talanta 131:480–489
Enot DP, Lin W, Beckmann M, Parker D, Overy DP, Draper J (2008) Preprocessing, classification modeling, and feature selection using flow injection electrospray mass spectrometry metabolite fingerprint data. Nat Protoc 3:446–470
Heux S, Fuchs TJ, Buhmann J, Zamboni N, Sauer U (2012) A high-throughput metabolomics method to predict high concentration cytotoxicity of drugs from low concentration profiles. Metabolomics 8:433–443
Oliveira AP, Dimopoulos S, Busetto AG, Christen S, Dechant R, Falter L, Haghir Chehreghani M, Jozefczuk S, Ludwig C, Rudroff F, Schulz JC, González A, Soulard A, Stracka D, Aebersold R, Buhmann JM, Hall MN, Peter M, Sauer U, Stelling J (2015) Inferring causal metabolic signals that regulate the dynamic TORC 1-dependent transcriptome. Mol Syst Biol 11:1–15
Palma P, Famiglini G, Trufelli H, Pierini E, Termopoli V, Cappiello A (2011) Electron ionization in LC-MS: recent developments and applications of the direct-EI LC-MS interface. Anal Bioanal Chem 399:2683–2693
Seemann B, Alon T, Tsizin S, Fialkov AB, Amirav A (2015) Electron ionization LC-MS with supersonic molecular beams – the new concept, benefits and applications. J Mass Spectrom 50:1252–1263
Lehotay SJ, Sapozhnikova Y, Mol HGJ (2015) Current issues involving screening and identification of chemical contaminants in foods by mass spectrometry. TrAC-Trends Anal Chem 69:62–75
Alechaga E, Moyano E, Galceran MT (2015) Wide-range screening of psychoactive substances by FIA-HRMS: identification strategies. Anal Bioanal Chem 407:4567–4580
Paglia G, Kliman M, Claude E, Geromanos S, Astarita G (2015) Applications of ion-mobility mass spectrometry for lipid analysis. Anal Bioanal Chem 407:4995–5007
May JC, Goodwin CR, McLean JA (2015) Ion mobility-mass spectrometry strategies for untargeted systems, synthetic, and chemical biology. Curr Opin Biotechnol 31:117–121
McCooeye M, Kolakowski B, Boison J, Mester Z (2008) Evaluation of high-field asymmetric waveform ion mobility spectrometry mass spectrometry for the analysis of the mycotoxin zearalenone. Anal Chim Acta 627:112–116
Nanita SC (2014) The future of pesticide residue analysis forecasted by advances in mass spectrometry. Proceedings of the 10th European Pesticide Residues Workshop (EPRW) (O-002), 30 June–3 July 2014, Dublin, Ireland
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The authors thank Barbara Larsen (DuPont Co.) for helpful discussions and comments.
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Nanita, S.C., Kaldon, L.G. Emerging flow injection mass spectrometry methods for high-throughput quantitative analysis. Anal Bioanal Chem 408, 23–33 (2016). https://doi.org/10.1007/s00216-015-9193-1
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DOI: https://doi.org/10.1007/s00216-015-9193-1