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APCI source with heated nebulizer LC inlet

The origins of atmospheric pressure chemical ionization sources combined with mass spectrometry can be found in the 1960s in studies of ions in flames[1] and of ion chemistry in corona discharges up to atmospheric pressure[2].The first application of APCI combined with mass spectrometry for trace chemical analysis was by the Franklin GNO Corporation who in 1971 developed an instrument combining APCI with ion mobility and mass spectrometry[3]. Horning, Carroll and their co-workers in the 1970s at the Baylor College of Medicine (Houston, TX) demonstrated the advantages of APCI for coupling gas chromatography (GC)[4] and liquid chromatography (LC)[5] to a mass spectrometer. High sensitivity and simple mass spectra were shown in these studies.[5] For LC-MS, the LC eluate was vaporized and ionized in a heated metal block. Initially, a 63Ni foil was used as a source of electrons to perform ionization. In 1975, a corona discharge electrode was developed, providing a larger dynamic response range.[6] APCI with the corona discharge electrode became the model for modern commercially available APCI interfaces.[7]

In the late 1970s an APCI mass spectrometer system (the TAGA, for Trace Atmospheric Gas Analyzer), mounted in a van for mobile operation, was introduced by SCIEX[8][9], providing high sensitivity for monitoring polar organics in ambient air in real time. In 1981 a triple quadrupole mass spectrometer version was produced, allowing real-time direct air monitoring by APCI-MS/MS. A similar platform was used for the SCIEX AROMIC system (part of the CONDOR contraband detection system developed together with British Aerospace) for the detection of drugs, explosives and alcohol in shipping containers at border crossings, by sampling the interior airspace[10][11].

In the mid-1980s and into the early 1990s , the advantages of performing LC/MS with APCI and with electrospray, both atmospheric pressure ionization techniques, began to capture the attention of the analytical community. Together they have dramatically expanded the role of mass spectrometry in the pharmaceutical industry for both drug development and drug discovery applications. The sensitivity of APCI combined with the specificity of LC-MS and LC-MS/MS often makes it the method of choice for the quantification of drugs and and drug metabolites.[12]


flames[1]

  1. ^ a b Knewstubb, PF; Sugden, TM (1960). "Mass-Spectrometric Studies of Ionization in Flames. I. The Spectrometer and its Application to Ionization in Hydrogen Flames". Proc. Roy. Soc. London. A255: 520–535.
  2. ^ Shahin, MM (1966). "Mass‐Spectrometric Studies of Corona Discharges in Air at Atmospheric Pressure". J. Chem. Phys. 45: 2600–2605.
  3. ^ Collins, DC; Lee, ML (2002). "Developments in Ion Mobility-Mass Spectrometry". Anal. Bioan. Chem. 372: 66–73. In early 1971, when IMS was referred to as plasma chromatography (PC), the Franklin GNO Corporation developed the first commercial ion mobility spectrometer–mass spectrometer (IMS–MS) and demonstrated its use as a detector for the identification and analysis of trace amounts of oxygenated compounds (i.e. 1-octanol and 1-nonanol).
  4. ^ Horning, E. C.; Horning, M. G.; Carroll, D. I.; Dzidic, I.; Stillwell, R. N. (1973-05-01). "New picogram detection system based on a mass spectrometer with an external ionization source at atmospheric pressure". Analytical Chemistry. 45 (6): 936–943. doi:10.1021/ac60328a035. ISSN 0003-2700.
  5. ^ a b Horning, E. C.; Carroll, D. I.; Dzidic, I.; Haegele, K. D.; Horning, M. G.; Stillwell, R. N. (1974-11-01). "Atmospheric pressure ionization (API) mass spectrometry. Solvent-mediated ionization of samples introduced in solution and in a liquid chromatograph effluent stream". Journal of Chromatographic Science. 12 (11): 725–729. doi:10.1093/chromsci/12.11.725. ISSN 0021-9665. PMID 4424244.
  6. ^ Carroll, D. I.; Dzidic, I.; Stillwell, R. N.; Haegele, K. D.; Horning, E. C. (1975-12-01). "Atmospheric pressure ionization mass spectrometry. Corona discharge ion source for use in a liquid chromatograph-mass spectrometer-computer analytical system". Analytical Chemistry. 47 (14): 2369–2373. doi:10.1021/ac60364a031. ISSN 0003-2700.
  7. ^ Byrdwell, William Craig (2001-04-01). "Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids". Lipids. 36 (4): 327–346. doi:10.1007/s11745-001-0725-5. ISSN 0024-4201. PMID 11383683.
  8. ^ Cappiello, Achille (2007). Advances in LC-MS Instrumentation. Netherlands: Elsevier. pp. 11–26. ISBN 9780444527738.
  9. ^ Thomson, BA; Davidson, WR; Lovett, AM (1980). "Applications of a Versatile Technique for Trace Analysis: Atmospheric Pressure Negative Chemical Ionization". Environmental Health Perspectives. 36: 77–84.
  10. ^ Pasilis, Sofie P.; Van Berkel, Gary J. (2010). "Modern Atmospheric Pressure Surface Sampling/Ionization Techniques". In Trantor, George E.; Koppenaal, David W. (eds.). Encyclopedia of Spectroscopy and Spectrometry. London: John Lindon. pp. 819–829.
  11. ^ Government of Canada, Public Services and Procurement Canada (1991). "On-Site Sampling and Detection of Drug Particles" (PDF). publications.gc.ca. Retrieved 2022-04-21.
  12. ^ Taylor, Lester C. E.; Johnson, Robert L.; Raso, Roberto (1995-05-01). "Open access atmospheric pressure chemical ionization Mass spectrometry for routine sample analysis". Journal of the American Society for Mass Spectrometry. 6 (5): 387–393. doi:10.1016/1044-0305(94)00124-1. ISSN 1044-0305. PMID 24214220.
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