R. K. Mitchum W. A. Korfmacher
Instrumentation
Department of Health and Human Services Food and Drug Administration National Center for Toxicological Research Jefferson, Ark. 72079
Atmospheric Pressure Ionization Mass Spectrometry
Although it is still somewhat novel and not widely used, the technique of atmospheric pressure ionization mass spectrometry (APIMS) represents a highly valuable analytical tool in the growing assortment of ionization sources now available to the mass spectroscopist. The technique is dif ferent from other ionization methods because sample ionization occurs at atmospheric pressure and outside the vacuum system, while for other mass spectrometric sources sample ioniza tion occurs at a reduced pressure in side the vacuum envelope. In contrast to the low-pressure regime, chemical equilibrium is attained in an atmo spheric pressure ion source while all other sources provide mixtures of unequilibrated ions and neutrals. This unique feature is responsible for the method's high sensitivity of detection (subpicogram limits) and its selectivi ty. APIMS has been successfully ap plied to the determination of compo nents of biological samples, air sam ples, and environmental samples, and has been directly interfaced to both gas chromatographic (GC) and liquid chromatographic (LC) systems. This article summarizes the principles of the APIMS technique and lists many applications where it has been used. For a more lengthy recent review of APIMS see Carroll et al. (2). Principles Figure 1 shows a schematic diagram of an APIMS system. The ion soilrce, which is at atmospheric pressure, has This article not subject to U.S. Copyright Published 1983 American Chemical Society
an orifice (typically 20-50 μπι) through which ions enter the mass an alyzer. The MS system is differential ly pumped so the quadrupole rods and electron multiplier are in a high-vacu um (10~ 6 torr) region. The makeup gas (referred to as the carrier gas by some investigators) has several functions. First, it sweeps the active API source volume, providing for continuous cleaning. Second, ei ther the makeup gas or gases added to it can act as the chemical ionization reagent gas. Third, the makeup gas acts as a carrier gas to sweep the sam ple into the active ionization volume in a manner similar to the makeup gas used in an electron capture detector (ECD). The samples may be intro duced by evaporation from a platinum
Electrical Feedthrough
probe, as solutions, or as gas or liquid chromatographic effluents. Sample molecules are ionized by mechanisms that depend on the reagent gas. Pri mary ionization is accomplished either via the high energy β radiation emit ted from a 63 Ni foil or via a corona dis charge. The ions entrained in the car rier gas enter the mass analyzer via a free jet expansion through the source aperture. The Background Spectrum. The ion-molecule reactions observed at at mospheric pressure depend largely on the specific makeup gas and on gas phase reagents that may or may not
Quartz Vaporizer Carrier In Probe Sweep In
63
Probe Guide
Carrier In — Probe Sweep In
Field Shield 95% Transparent
Ni Foil
Quadrupole
50-μm Orifice
Carrier Out Source Carrier Out Source Diffusion Pump
L2
L1 L4 L3 L5
Analyzer Diffusion Pump
Figure 1. APIMS schematic ANALYTICAL CHEMISTRY, VOL. 55, NO. 14, DECEMBER 1983 · 1485 A
AH + B+ - • A+ + BH (hydride abstraction)
(5)
A" + BH — AH + B~ (proton transfer)
(6)
A+ + BC -> A + B + + C (dissocia tive charge transfer) (7) A+ + Β — AB+ (addition)
(8)
+/
A + B - + M — AB+/- + M (clustering)
(9)
AX + 0 2 ~ -* A 0 - + OX (sub stitution) (10)
m/z Figure 2. Typical positive ion background spectrum for APIMS showing various cluster ions Reprinted from Reference 10
have been intentionally added. Typi cally, prepurified nitrogen gas is em ployed and is further purified by pass ing it through 13X molecular sieves. The primary ionization process in volving the decay of 63 Ni yields ap proximately 30-40 ionization events along the ionization track and forms primarily N + and N 2 + ions (2). Alter natively, a corona discharge produces comparatively lower energy electrons, resulting in fewer ionization events. However, this is offset by the greater number of electrons produced and available for ionization of the neutral makeup gas. This primary reaction is followed by third-order ion-molecule clustering reactions yielding Ν2·Ν2+ and N 2 -N+ clusters (3-6). In addition, due to trace water contamination, third-order clustering reactions in volving the hydrated proton ( H 3 0 + ) are observed (4, 7). In addition to these reactions, the formation of clus ters of nitrogen molecules and hydronium ions are observed at atmospheric pressure. Often trace levels of O2 are present, leading to the production of C>2+ and N O + ions. A typical positive ion background mass spectrum is shown in Figure 2. In the negative ion mode, the condi tions in the API source are similar to those of an ECD (5, 8). Ionization oc curs by electron capture or ion-mole cule reactions involving a reagent ion such as O2 - . When the source is very clean, with N2 as the makeup gas and also as a third body to collisionally stabilize the product ions, and when trace levels of oxygen are present, the background spectrum contains three
major ions, m/z 32, 60, and 88. The first ion is 0 2 ~ formed by resonant electron capture. Two possible routes have been suggested for the formation of the other two ions. The first route involves nitrogen clustering reactions with 0 2 ~ (6, 9). A second series of re actions relies on the presence of small traces of C 0 2 and leads to the forma tion of the CO3- ion (10,11). At high er oxygen concentrations, O4 - and N 2 clusters with 0 4 ~ are observed. In the presence of trace amounts of H 2 0 , hy drates of 0 2 ~ and O4 - are observed. Typically, Cl~ ions will also be ob served in the background spectrum; these result from chlorinated impuri ties present at ultralow levels in the makeup gas. Positive and Negative Ion Reactions with Samples The addition of a trace component (sample) to the API source may give rise to either positive or negative ions, or both. These are referred to as "sec ondary ions." The major modes of sec ondary ion formation are shown in Re actions 1-10, where M is any third body: A + / - + Β — A + B+/- (charge transfer)
(1)
A + e~ + M ^ - A ~ + M (associative electron capture) (2) AX + e~ -*• A + X - (dissociative electron capture) (3) AH+ + Β — A + BH+ (protonation) (4)
1486 A · ANALYTICAL CHEMISTRY, VOL. 55, NO. 14, DECEMBER 1983
The reactions observed at atmo spheric pressure represent a system at thermodynamic equilibrium in which several reaction schemes may be in volved. Positive ion reactions in high pres sure (~1 torr) ion sources have been well documented (12). Research into negative chemical ionization (NCI) is very active, and interest in NCI tech niques and applications is growing rapidly (13). For example, it has been demonstrated that Reaction 10 plays an important role in the negative ion chemistry of polychlorinated aromatics and aliphatic and aromatic mole cules having a reactive site (14-17). Detection Limit. The main advan tages of the APIMS technique are the low detection limit and the inherent ease of GC interfacing. API has the ca pability of being much more sensitive than electron impact (EI) (6-8). The absolute ionization efficiency for EI is 0.01-0.1% of the sample molecules in troduced into the vacuum system, while for API the initial ionization ef ficiency is almost 100% (6, 8). Of course, not all the ions produced in the API source enter the mass analyz er (due to wall losses, lens transmis sion losses, etc.), but the large differ ence in the initial ionization efficiency is still a major advantage. It has been calculated (1, 6) that a detection limit of 1-4 Χ 1 0 - 1 4 g should be achieved using APIMS. The experi mental detection limit of the APIMS technique was demonstrated early in its development by Caroll et al. (18), who showed that this method could be used to detect compounds at the sub program level. Figure 3 shows the re sponse obtained for injections of 0.15 to 1.2 pg of 2,6-dimethyl-7-pyrone (18). For this work, the standards were injected in 1-/ÎL volumes of benzene through a cold septum mounted on the APIMS sample inlet. The protonated molecular ion, MH + , was monitored. Selectivity. The thermal nature of the ion-molecule reactions at high pressure in a 63 Ni API source dictates the terminal ions observed. Therefore, in the analysis of mixtures containing components of differing proton affini-
The Analytical Approach The Analytical Approach Edited by Jeanette G. Grasselli
6:,
ty, the dominant ion resulting from proton transfer is the component with the highest proton affinity. Similarly, for charge exchange processes, the component with the lowest ionization potential dominates the spectrum. Also, negative ion formation via associative electron capture creates terminal ions via subsequent charge transfer processes and is dependent upon the electron affinity of the molecules involved. The relative abundance of the response derived from the analysis of a mixture is dependent on the equilibrium constants for the ion-molecule reactions, and therefore depends on both the temperature and the concentration of reactants. These interactions constitute a critical limitation for the direct analysis of mixtures via
Ni APIMS. However, the analysis of mixtures via GC or capillary GC eliminates this factor since the mixture components are separated chromatographically. API vs. CI It is important to distinguish between APIMS and chemical ionization mass spectrometry (CIMS). The most obvious difference is the source pressure (760 torr for API; 10" 2 to 1 torr for CI). This difference in operating pressure has several effects. In APIMS, the ion-molecule or electronmolecule reactions occur at atmospheric pressure where long residence times and the field-free drift region govern the reaction dynamics. The long residence time, typically 2-5 s de1200
Jeanette G. Grasselli, Editor Brings together 52 papers from The Analytical Approach column in ANALYTICAL CHEMISTRY. Provides unique approaches to analytical science and focuses on real-world problems. Discusses topical and interesting subjects such as the analysis of the JFK assassination bullets, Mt. St. Helens ash, flavor changes in food, and failure mechanisms in spacecraft parts. Written in a "popular" style yet is highly informative. Will serve as a teaching aid in higher education or as a guide in corporate training programs on analytical capabilities.
20 s
600
300
150 Blank
Time Figure 3. Response observed for femtogram samples (benzene was the solvent) of 2,6-dimethyl-7-pyrone injected directly into the API source The MH + ion was monitored. Reprinted from Reference 18
CONTENTS
Sections include: • Production Processes • Products • Environmental
Total Ion Current
• Toxicity
Benzo[a]pyrene
• Forensic • Miscellaneous 240 pages. (1983) Clothbound LC 82-22618 ISBN 0-8412-0753-4 US & Canada $29.95 Export $35.95 A paperbound student edition is available in bulk quantity. For price and ordering information, call toll tree 800-424-6747. Order f r o m : American Chemical Society Distribution Office — 50 1155 Sixteenth St., N.W. Washington, DC 20036 or CALL T O L L FREE 800-424-6747 and use your credit card.
Benzanthracene
Anthracene m/z Figure 4. Results obtained for three PAHs analyzed by the LC/APIMS system Single-ion monitoring data are compared with the total ion current results. Reprinted from Reference 21
1488 A · ANALYTICAL CHEMISTRY, VOL. 55, NO. 14, DECEMBER 1983
At Magnetic Peripherals Inc. success has many directions for a ..
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ANALYTICAL CHEMISTRY, VOL. 55, NO. 14, DECEMBER
1983
pending on the aperture diameter and the physical design of the source, allows sufficient collisions with reagent molecules or electrons to ionize completely all the trace organic molecules introduced into the source. Due to the high neutral molecular density at atmospheric pressure, ions attain thermal equilibrium in a relatively short period, typically after a few collisions with the carrier gas. Ion loss due to recombination and diffusive losses to the reaction chamber represent the predominant loss processes at atmospheric pressure. In contrast, CIMS represents a lower pressure regime. For thermal equilibrium to be reached at pressures approaching 1 torr, relatively long residence times are required, typically on the order of a few milliseconds. Typically, nonequilibrium conditions exist in analytical CI sources, resulting in ionization of only a portion of the sample introduced. Also, the lack of thermal equilibration in a CI source leads to product ions that are excited and may not be collisionally stabilized. These CI product ions are then more likely to fragment than similar API product ions would be. Instrumental Variations As with other techniques, APIMS has gone through various design changes and applications. Following the original 63 Ni ionization design (5), a corona discharge model was developed. APIMS sources have been interfaced with an LC and a GC. APIMS has also been used for real-time environmental monitoring. Recent advances include the development of an API source for a standard Finnigan 4000 quadrupole MS and a design to accept nonvolatile samples. These developments will be discussed in this section. Corona Discharge vs. 63 Ni Source. While the earliest work in APIMS was performed by Horning and co-workers (5,18) using a 63 Ni foil as an electron source, the corona discharge ion source followed shortly thereafter. Horning et al. developed the corona discharge API source specifically for the LC/APIMS system (19-21). The advantage of the corona discharge source is primarily that a much larger analytical dynamic range is achieved and that both equilibrated and nonequilibrated conditions may be used. The reactant ion concentration is about 100 times that of the 63 Ni source (2i).The disadvantages of the corona discharge ion source include continual erosion of the discharge tip and orifice clogging due to sputtered material (6). The 6 3 Ni source has the advantage of being a simple, reliable source of electrons that undergo ther-
Injector Glass Capillary Adapter
Heat-Shrink Tubing Source Volume
Quartz Injector Tube
50-μm
Aperture 20-m Capillary Column
63
Νi Foil
Pt-lr Capillary Makeup Gas Inlet
Overflow Gas Outlet
Vacuum Housing Oven Wall
Figure 5. Schematic diagram of a glass capillary GC/APIMS system Reprinted from Reference 25
mal reactions. In addition, use of the 63 Ni foil as the ion source for APIMS can provide useful information on the reactions that occur in an ECD (8, 22, 23). Dzidic et al. (24) have compared the positive ion response of 63 Ni and corona discharge API sources. A corona discharge API source can be used to study nonequilibrated pro cesses; the ionic products depend upon the ion source geometry. The distance of the discharge from the ion exit aperture will determine the domi nant ions in the spectrum. The advan tage this source has over a 63 Ni source is the large electron flux producing a greater dynamic range and the ability to analyze mixtures without observing a terminal ion spectrum. This advan tage has its greatest utility in real time monitoring of industrial emis sions, breath analysis, and workplace monitoring. The corona discharge source has a sensitivity similar to the 63 N i source.
LC/APIMS. Horning and co-work ers quickly realized the potential for interfacing an HPLC with an APIMS (19-21). For this work, isooctane was used as the HPLC solvent. Reagent ions (C4Hg+) in the source protonated polycyclic aromatic hydrocarbons (PAHs) to give MH+ ions (21). Figure 4 shows the results from an LC/ APIMS analysis of anthracene, benzanthracene, and benzo(a)pyrene. It can be seen that while the latter two PAHs were not separated chromatographically, they were selectively de tected using the multiple ion detection (MID) technique. GC/APIMS. The unique suitability for combined GC/APIMS was investi gated by Horning et al. (5,18). The in herent problem in interfacing conven tional MS sources to accept either the direct or split flow of a GC has been the pressure and volume gradient from the GC at atmospheric pressure to the source at subambient pressure
(a)
(
