apci/appi for synthetic polymer analysis -...

APCI/APPI FOR SYNTHETIC POLYMER ANALYSIS

P. Terrier,1 B. Desmazieres,2 J. Tortajada,2 and W. Buchmann2*1Department of Chemistry, University of British Columbia, 2036 Main Mall,V6T 1Z1 Vancouver, British Columbia, Canada2Laboratoire Analyse et Modelisation pour la Biologie et l’Environnement,Universite d’Evry val d’Essonne, CNRS UMR 8587/CEA,Batiment Maupertuis, Bd. Francois Mitterrand, 91025 Evry, France

Received 31 July 2009; received (revised) 10 February 2010; accepted 10 February 2010

Published online 18 January 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mas.20302

Modern mass spectrometry of synthetic polymers involves softionization techniques. Whereas matrix-assisted laser desorp-tion/ionization (MALDI) and electrospray (ESI) are employedroutinely, atmospheric pressure chemical ionization (APCI) andmore recently atmospheric pressure photoionization (APPI) areused to a lesser extent. However, these latter ionization methodscoupled to liquid-phase separation techniques create newopportunities for the characterization of polymers, especiallyfor low molecular weight compounds or for the polymers thatare poorly ionizable by the usual methods. After a part devotedto the description of classical MS methods employed forpolymer analysis (MALDI, ESI, and their use with chromatog-raphy), APCI and APPI techniques will be described,discussed, and selected examples will present the interest ofthese ionization sources (or interfaces for LC/MS) in the field ofpolymer analysis. # 2011 Wiley Periodicals, Inc., Mass SpecRev 30:854–874, 2011Keywords: APCI; APPI; polymers; atmospheric pressureionization; chemical ionization; photoionization; LC/MS

I. INTRODUCTION

Synthetic polymers are often complex mixtures, due to thesynthetic techniques employed (Flory, 1953). To gain a betterunderstanding and control of the polymerization mechanisms, aswell as the chemical and physical properties of the materials,powerful analytical methods are required. Conventional methodsof characterization include size exclusion chromatography(SEC), viscosity, light scattering, and nuclear magnetic reso-nance (NMR). The use of these analytical techniques is nowfrequently completed by structural studies by mass spectrometry(MS) (Hanton, 2001; Montaudo & Lattimer, 2002; Pasch &Shrepp, 2003). Combined with liquid chromatography (LC)separations, MS yields accurate structural information, whereasthe most common detectors such as ultraviolet (UV), refractiveindex (RI), and light-scattering (LS) provide only relatively poorstructural information (Nielen & Buijtenhuijs, 1999; Murgasova& Hercules, 2002).

The introduction and the development of soft ionizationmethods such as electrospray ionization (ESI) (Fenn et al., 1989),and matrix-assisted laser desorption/ionization (MALDI) (Karas

&Hillenkamp, 1988; Tanaka, 2003) have significantly improvedthe ability of MS analysis for polymer analysis. Thesetechniques, which allow the detection of intact polymer chains,are now routinely used. One of the most important particularitiesof modern MS resides in its ability to provide the molecularweight of individual chains of a polymer. From this measure ofmass, one can deduce the nature of the repeat units and that of theend-groups. The presence of side-products can be detected, andcompounds like cyclic species or chainswith alternative ends canbe identified (Montaudo et al., 1996; Jackson et al., 1997).Composition and sequence of copolymers (vanRooij et al., 1998;Terrier et al., 2005, 2006) or branching can also be studied(Lederer et al., 2006; Clark et al., 2007). Thus, MS studies canreadily provide qualitative information. In addition, molar massdistributions can be appreciated through the determination ofaverage molecular weights, polymerization degrees, and poly-dispersity indices. However, the quality of such information ismore questionable. Indeed, MS can yield incorrect quantitativedata, especially for wide polymer distributions (Montaudo et al.,1995a).

Atmospheric pressure chemical ionization (APCI) andmorerecently atmospheric pressure photoionization (APPI) arealternative methods to MALDI and ESI. Few articles describedthe use of these ionization methods in the field of polymeranalysis. However, they create new opportunities for thecharacterization of polymers, especially for low molecularweight compounds or for the polymers, which are poorlyionizable by the usual methods (MALDI and ESI). Theadvantages and drawbacks of the classical MS methods usedfor polymer analysis will be presented at first. Next, the physicalprinciples of the APCI and APPI techniques will be described.Finally, the interest of these latter ionization sources (orinterfaces for LC/MS) will be presented through selectedexamples.

II. COMMON MS TECHNIQUES FOR POLYMERANALYSIS

A. MALDI-MS Versus ESI-MS

Matrix-assisted laser desorption/ionization (MALDI) and ESIare now the most commonly employed ionization sources for theMS analysis of synthetic polymers, as attested to the literaturepublished during the few last years (Peacock & McEwen, 2006;Weidner & Trimpin, 2008). Both techniques are well-known toproduce quasi-molecular ions for masses up to 100,000Da, withno or just a few fragmentations depending on the fragility of thepolymer and of the harshness of the instrumental parameters.

Mass Spectrometry Reviews, 2011, 30, 854– 874# 2011 by Wiley Periodicals, Inc.

————*Correspondence to: W. Buchmann, Universite d’Evry Val d’Essonne,

Laboratoire Analyse et Modelisation, pour la Biologie et l’Environ-

nement (LAMBE, UMR 8587), Batiment Maupertuis, Bd F.

Mitterrand, 91025 EVRY Cedex, France.

E-mail: [email protected]

Among these two ionization techniques, MALDI is by farconsidered as the most appealing because it produces mainlysingly-charged ions (typically, cationic adducts such as MNaþ,MKþ or the protonated species MHþ) with nearly no fragmenta-tion (Pasch & Shrepp, 2003). The MALDI source is usuallycombined with a TOF analyzer (or a TOF-TOF), which providesa wide mass range, a good sensitivity, and a relatively highresolution (10,000–30,000). After a quick step devoted to thepreparation of the sample, a mass spectrum can be recorded in afew minutes, and a polymeric distribution is immediatelydisplayed. A series of various polymeric materials can beanalyzed from different spots on the same MALDI plate with nomemory effects. However, the apparent simplicity of use ofMALDI-MS hides inherent drawbacks of the technique. Theobtained results can strongly depend upon sample preparation.The preparation step involves the mixing of the polymer with asalt (e.g., CH3COONa) and a small organic compound (called the‘‘matrix’’), which absorbs at the laser wavelength. The functionof the salt is to enhance the cationization process. The role of thematrix is to protect the sample and favor the desorption–ionization process. The choice of a suitable matrix is decisive forthe success of the MS experiment. The matrix is usually selectedempirically on a trial/error basis from a set of compounds thathave been successfully tested by others (Pasch & Shrepp, 2003).If a polymer does not yield ions with all the knownmatrices, thenone cannot deduce that this compound will never give ions with anew matrix. Another drawback of the MALDI-MS techniqueconcerns the lack of spot-to-spot, shot-to-shot reproducibilitydue to a non-homogeneous crystallization in some cases, or dueto layer formation within the matrix (Terrier et al., 2005).Moreover, a major issue is the possibility of discriminationeffects that lead to the preferential desorption–ionization ofcertain chains against others. The ionization yields clearlydepend on the chain size and the nature of the end-groups (not tomention the nature of the repeat units). In the case of blends, therelative quantification of the different polymers is problematic. Inthe case of broad polymer distributions (Mw/Mn> 1.10), averagemolar masses are underestimated because the lighter chains aremore efficiently detected than the heavier ones. However, for theless polydisperse polymers (Mw/Mn< 1.10), average molarmasses values are obtained in agreement with other methods(SEC, viscometry. . .) (Lloyd et al., 1995; Montaudo et al.,1995a). At last, the low mass range is affected by the presence ofions that arise from the matrix.

Compared to MALDI-MS, ESI-MS (without on-linechromatographic separation) has been used to a lesser extentfor polymer analysis because it provides several charge statesfrom a single molecule. Thus, an additional complication canarise with charge state distributions overlapping chain lengthdistribution. This overlapping can lead to very complex massspectra in the case of high-mass polymers. Deconvolutiontechniques can be employed to simplify the mass spectra bypresenting one molecular weight per chain, but instruments witha high resolving power are required to resolve isotope peaks andto separate isobaric ions. ESI typically operates at atmosphericpressure and ambient temperature, and the ionization process isvery soft; thus no fragmentation is induced. The gaseous ionsproduced from synthetic polymers often result from cationiza-tion, just as in MALDI. The spray solvent, and the chosen addedsalt (alkali metal cations) influence theMS results. ESI is reputedto be less tolerant to the presence of buffers or additives than

MALDI, and is also less suited to analyze moderately polarpolymers. ESI combinedwith triple quadrupole or hybridQ-TOFinstruments allows tandem mass spectrometry experiments. Inaddition, with the LIT-orbitrap and FT-ICR, the high resolutionobtained is advantageous. As in MALDI-MS, the efficiency ofthe ionization process can depend on the nature and the length ofthe chains as well as on the ionization conditions. Moreover,whatever the ion source, the transmission of the ions to thedetector and the detection of the ions can bemass-dependent, andtherefore can also be prone to mass discrimination effects. As aconsequence, the estimation of average molar masses can beerroneous on a wide mass range.

B. On-Line LC-MS with an ESI Interface

Although ESI-MS can be naturally used to analyze fractionscollected after a chromatographic separation (the off-linecoupling with SEC has frequently been reported), the ESI sourceis particularly suited as an interface for direct LC/MS (Nielen &Buijtenhuijs, 1999; Murgasova & Hercules, 2002). This kind ofinterface is sufficiently versatile to accommodate flow rates fromnanoliters per minutes up to 1mL/min that allow direct couplingto LC columnswith inner diameters of 4.6mmor less without theneed of post-column splitting. However, the range of eluents andadditives is limited to rather polar eluents and volatile additives.Different modes of LC separation can be associated to MSdetection: size exclusion chromatography, also known as gelpermeation chromatography (SEC or GPC), reversed-phaseliquid chromatography (RPLC), and normal phase liquidchromatography (NPLC) in the isocratic mode (constant mobilephase composition) or in the gradient mode. However, thecompatibility of the ESI interface with NPLC is not satisfyingbecause apolar hydrocarbon solvents (e.g., hexane, toluene. . .)used as eluent are not suitable for the ESI process (Voyksner,1997). Mixtures of hydrocarbons and more polar solvents, suchas isopropanol can be used, but sensitivity may not be high. Forpolymer analysis, the advantages of the LC/MS coupling include(i) reduction of the complexity of the mass spectrum that wouldbe obtained from the entire sample (isobaric ions, isotopiccontributions), (ii) reduction of signal suppression effects toallow the observation of higher mass or lower abundanceoligomers. The other major interests of the LC/MS couplingare to enable the understanding of the chromatographic behaviorand enable the differentiation between in-source thermaldecompositions (or up-front fragmentations in the interfaceregion of the mass spectrometer) and the real presence of low-mass oligomers.

C. Off-Line LC-MS with MALDI-MS

Endeavors to directly associate LC (mainly SEC) and MALDI-MS have never been fully satisfying and the coupling LC/MALDI-MS has remained off-line. Generally, fractions col-lected after LC separation are subsequently analyzed withMALDI-MS. SEC is the most popular LC method for syntheticpolymer analysis, and is employed to determine average molarmasses of polymers. Because this technique is generallyassociated with a differential refractive detector, which providesno structural information, the coupling with MS is particularlyinteresting. SEC allows the separation of compounds as afunction of their hydrodynamic volumes in solution. The larger

APCI/APPI FOR SYNTHETIC POLYMER ANALYSIS &

Mass Spectrometry Reviews DOI 10.1002/mas 855

molecules (higher molecular weights) elute first followed by thesmaller compounds. After a calibration procedure with narrowlydispersed standard polymers (typically polystyrene standards),molecular masses of unknown polymers can be deduced fromretentionvolumes.However, suitable calibrants cannot always befound and the fact that two different polymers with the samemolecular weight might adopt different conformations and thusoccupy different hydrodynamic volumes can lead to erroneousresults. To solve this problem, a variant of the SECmethod basedon intrinsic viscosity measurements can be applied to provide auniversal calibration and determine accurate molecular weightsof polymers, for which standards are not available (Grubisic,Rempp, & Benoit, 1967). With the same intention, the mostsignificant application of an off-line SEC/MALDI-MS couplingconcerns the accurate calibration of the SEC device (Montaudoet al., 1995b). Each SEC fraction contains a less polydispersesample than the entire polymer, and is less prone to the MSdiscrimination effects mentioned above. Therefore a reliableaverage mass can be measured. Absolute calibration curves canbe obtained for SEC. When MALDI and SEC are combined, thelimitations related to mass discriminations by MALDI areovercome, and there is no longer a need for a calibration standardfor the SEC analysis. Other LC techniques have been combinedwith MALDI-MS detection, including LC at critical conditions.

III. APCI AND APPI SOURCES

A. APCI and APPI Among the New Ion SourcesAvailable for Polymer Analysis

Compared to theMALDI or ESI ionization techniques, APCI andAPPI have been less used for synthetic polymer analysis. Thereasons are numerous.MALDI and ESI are both extensively usedfor biomolecule analysis, and are now widely available in massspectrometry laboratories. The implementation of MALDI isvery simple and quick. MALDI and ESI are generally preferredover APCI and APPI because these latter techniques arereputedly efficient for low molecular weight compounds only.MALDI and ESI attain the most extended mass ranges, whereasthermal decompositions are a common feature of APCI for largefragile compounds. Therefore, APCI and APPI are generallyconsidered as alternative ionization methods to ESI, and arereserved to the analysis of low mass molecules or low polaritycompounds. To characterize large or unionizable polymers,APCI has been recently interfaced with pyrolysis to analyze thethermal degradation products of polymers (Whitson et al., 2008).Concerning theAPPI source, its commercialization is recent, andonly a few articles deal with its use for polymer analysis.

New ionization methods have recently been applied topolymer analysis. MALDI experiments can now be carried out atatmospheric pressure (AP-MALDI) (Laiko, Baldwin, & Burlin-game, 2000; Doroshenko et al., 2002; Creaser et al., 2003;Hanton, Parees, & Zweigenbaum, 2006) with analyzers thatenable MSn experiments (Hanton, Parees, & Zweigenbaum,2006). The addition of matrix for laser desorption–ionizationexperiments can be bypassed with desorption ionization onsilicon (DIOS) (Lewis et al., 2003; Shen et al., 2004). Other newsurfaces have been described to avoid matrix addition (Peterson,2007). Among the various emerging ambient ionization techni-ques (Venter, Nefliu, & Cooks, 2008): desorption-electrosprayionization (DESI) (Takats et al., 2004; Jackson, Williams, &

Scrivens, 2006; Nefliu, Venter, & Cooks, 2006; Williams et al.,2007) and direct analysis in real-time (DART) (Cody, Laramee,& Durst, 2005), which are commercially available, have broughtpromising results. With these new techniques, the sample isanalyzed in the open atmosphere of the laboratory, and thesample preparation step is strongly simplified, if not eliminated.Unfortunately, DIOS and DESI ionization methods cannot bedirectly coupled with liquid chromatography, and their applic-ability has remained limited to low molecular weight polymers.With DART, only fingerprints of polymers were obtained afterincreasing the gas temperature (He) to 450–5508C to inducepyrolysis (http://www.jeolusa.com, 2008).

B. APCI Ionization

1. Description of the APCI Ion Source

What we call now ‘‘atmospheric pressure chemical ionization’’(APCI) was initially introduced as the ‘‘Corona source’’ byHorning and co-workers in the mid-1970s (Horning et al.,1974a,b; Carroll et al., 1975), as a new interface to couple LCwith MS. In the course of their studies of the ionization reactionsthat occur at atmospheric pressure, the ‘‘Corona source’’succeeded a 63Ni radiation source (Horning et al., 1973; Carrollet al., 1974). Both sources operated at atmospheric pressure, andcould produce electrons, as the heated filament of a classical CIsource. Historical reviews of the early developments of the APCItechnique among the other LC/MS interfaces are availableelsewhere (Niessen, 1998; Thomson, 1998; Abian, 1999).Although APCI is an old technique, its commercial success hadto wait for the development of ESI and LC/MS coupling in the1990s. APCI is nowadays commonly applied to the analysis ofcompounds of environmental and pharmaceutical interest(pesticides, polyaromatic hydrocarbons, drugs. . .).

A standard APCI source contains a heated pneumaticnebulizer and a high-voltage needle to produce a coronadischarge as depicted in Figure 1. The solution that containsthe analytes (directly introduced by infusion or from LC) israpidly dispersed into a fine mist of droplets in the nebulizer bythe coaxial air or N2 flow. The droplets are thermally vaporized ina heated probe (a non-conductive quartz tube or a ceramicmaterial). At the exit of the tube, a high voltage (3–5 kV) isapplied to a needle to produce a corona discharge (note that thepotential is not applied to the liquid unlike ESI). The appliedvoltage is variable to induce a constant current, typically of 1–5mA. When the needle is held at high positive potential, theneedle captures electrons (emits electrons when a negative highvoltage is applied). Owing to the electrons captured or emitted bythis corona discharge needle, a series of gas-phase chemicalreactions occur with the gas molecules of solvent (or air) presentin the source chamber. The so-formed ions react with thedesolvated analyte molecules to yield analyte ions. Theefficiency of this chemical ionization process is related to in-source collision frequencies, and is consequently better atatmospheric pressure than at low pressure of classical CI source.The APCI sources are known to yield stable and reproduciblesignals.

Atmospheric pressure chemical ionization (APCI) istypically preferred over ESI for the analysis of low molecularmass compounds (typically less than 1,000Da), and of species ofmedium to low polarity. Ideally, the sample should be thermally

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856 Mass Spectrometry Reviews DOI 10.1002/mas

stable and quite volatile. APCI is a soft-ionization technique, butless soft than ESI partly due to the fact that the vaporization of thesolvent is produced by a heated nebulizer kept at 350–4508C.Modern heated nebulizers can be used up to 6008C, or evenmore.However, this temperature refers to the heater temperature; theactual temperature of the inner wall of the quartz tube would beabout 100–1508C (Thomson, 1998), and the real temperature ofthe sample molecule could be even lower than that because thelargest part of the thermal energy is used for the moleculesvaporization. Therefore the sample would be submitted to alimited thermal stress.

2. APCI Formation of ions

The process of gas-phase ion formation in APCI differs from ESIin that there are two distinct steps: (1) solvent evaporation byheating after nebulization, and (2) ion formation initiated by thecorona discharge. APCI yields only singly charged ions. In thepositive-ion mode, protonated species (MHþ), radical cationsðMþ�Þ, and adducts (Mþ cation)þ, such asMNHþ

4 orMNaþ, canbe observed. Sometimes, several of these species can co-exist inthe same mass spectrum due to competitive formation pathways(Herrera, Grossert, & Ramaley, 2008). Whereas adduct for-mation with metals can be due to a thermospray mechanism, theformation of the (MHþ) or ðMþ�Þ ions in APCI requires a seriesof successive reactions in the gas-phase that involve chargeexchanges and/or proton transfers (Carroll et al., 1981). Mostreports in the literature used small compounds as models, andpolymers are rarely addressed. Table 1 presents some of the

possible gas-phase reactions in the positive-ion mode (Mrepresents the analyte molecule, S the solvent). These reactionsand several others that possibly occur in the ionization chamberin the positive-ion mode have been discussed recently (Herrera,Grossert, & Ramaley, 2008). Even if the ionization energy of N2

is higher than the solvent or the analyte, the corona dischargeformsNþ�

2 ions as primary ions from the excess N2 nebulizing gasmolecules (see Table 1, reaction (1)). Further gas-phase reactionscan take place with charge exchange and/or proton transfer.Reaction (2) in Table 1 shows the formation of the radical cationSþ., which can react with the analyte M to give either the analytemolecular ion Mþ. by charge exchange (reaction (3)), or aprotonated analyte MHþ by proton transfer (reaction (4)). Theradical cation Sþ. can also react with another S molecule to yielda protonated solvent molecule SHþ, or with a solvent cluster Sn(n> 1), to give a protonated solvent cluster SnH

þ by a hydrogenabstraction (reaction (5)). The latter species can react efficientlywith M to give MHþ (reaction (6)). It is important to note thatin APCI protonated solvent clusters can play a more importantrole that the protonated single solvent molecule itself (Sunner,Ikonomou, &Kebarle, 1988b; Sunner, Nicol, &Kebarle, 1988a).The ionization energies (IE) and proton affinities (PA) of thesamples, the solvent molecules, and ambient gas in the sourcemust be taken into account to rationalize the formation of ions inthe source. Thus, it is expected that the charge exchange reactions(2) and (3) as depicted in Table 1, occur with low IE analytes andsolvents. Themost commonly used solvents, polar (such aswater,methanol, acetonitrile for RPLC), or apolar (such as hexane,isooctane for NPLC) have a lower IE than N2 (see Table 2).

FIGURE 1. Schematic representations of a APCI source (A), and a APPI source (B) based on a in-line

geometry. (N.B. LC entry can be used for direct infusion.)



Regarding the analytes, molecular cations Mþ. can be formedfrom compounds that possess a low IE, as is the case witharomatic compounds (see toluene and styrene in Table 2). Goodcandidates are heterocyclic compounds (Holcapek et al., 2007)and polycyclic aromatic hydrocarbons (Herrera, Grossert, &Ramaley, 2008). Proton transfer—as shown in reaction (6) fromthe protonated solvent cluster SnH

þ towards the analyte M—occurs if the PA of the analyte is higher than that of the solventcluster Sn. In this case, signal-suppression effects can be expectedwith low PA analytes. Because the observed behavior is notalways what is expected from thermodynamic considerationswith isolated molecules, the species involved in the proton-transfer or charge-exchange reactions that occur in the APCIsource are more likely the solvated species than the fullydesolvated species (Herrera, Grossert, & Ramaley, 2008).

In the negative ion mode, deprotonated molecule anions(M�H�), radical anions ðM��Þ, and adducts (Mþ anion)� canbe formed. The radical anions ðM��Þ can arise from directelectron capture of thermal electrons produced by the coronadischarge with compounds having a positive electron affinity EA(Table 1 reaction (7)). Because oxygen has a positive electronaffinity EA, it can be ionized in such a manner, and act as areagent gas for analyte molecule (M) reactions (8)–(9)—asdepicted in Table 1. This charge-exchange reaction occurs if theelectron affinity of M is greater than that of O2. O2

�. formed inreaction (8) is a strong base in the gas-phase, and can react with asolvent molecule, S, or an analyte molecule, M, of higher gas-phase acidity, to yield, respectively, [S�H]� and [M�H]�

(reaction (10) and (12)). [S�H]� can also react with M togive [M�H]� by hydride abstraction (reaction (11)). Thus,

TABLE 1. Ionization mechanisms in APCI (þ)/APCI (�)

TABLE 2. Gas-phase IE and PA values of some compounds (solvents, source gas, and monomers)

from NIST Chemistry Webbook (Linstrom & Mallard, 2009)

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signal-suppression effects can be observed for compounds with alow gas-phase acidity. If the mobile phase contains a chlorinatedsolvent (chloroform, dichloromethane), then [MþCl]� adductions can also be formed. In the presence of organic acids, adductions such as [MþHCOO]� can be produced.

3. Factors That Influence the Performance of APCI

As with the other ionization methods, the nature and abundanceof the ions formed in APCI mainly depend on the analytestructure. They also depend on the solvent or mobile phase used(acetonitrile, methanol, toluene. . .) and on the presence of anyadditives (Kostiainen & Kauppila, 2009). Several authorsreported that the nature of solvent has a strong effect on ionformation, especially when there is a competition between MHþ

and Mþ. (Holcapek et al., 2007; Herrera, Grossert, & Ramaley,2008). Asmentioned above, the PA, IE, andEAof the analyte andof the solvents used are crucial. However, except for a fewmonomers or dimers, as shown in Table 2, the gas-phase PA andIE values are not available for polymers.

The APCI technique is known to be robust, because theionization is not affected by small variations in the nebulizing gaspressure and solvent flow rates. This remark is also true for thevoltage applied to the needle, or for the probe temperature(Herrera, Grossert, & Ramaley, 2008). A strong deviation fromthe optimal value of the needle current is necessary to record amarked effect in the absolute intensities (Holcapek et al., 2007).The nature of the ions observed in APCI also depends on thedistance between the corona needle and the analyzer entranceaperture—as discussed by several authors (Carroll et al., 1981;Sunner, Nicol, &Kebarle, 1988a; Sunner, Ikonomou, &Kebarle,1988b; Kolakowski, Grossert, & Ramaley, 2004). However, thisdistance cannot always be controlled on commercial sources. Asexpected for fragile compounds, a too high probe temperaturecan cause the decomposition of the sample in the source(Holcapek et al., 2007); however, this decomposition is limiteddue to solvent high flow rates and consequently shorter timesspent in the heated nebulizer. Indeed, the APCI technique usestypically high flow-rates such as 1mL/min (flow-rates ofstandard HPLC columns, 4.6mm ID).

The miniaturization of analytical devices is one of thecurrent trends in analytical chemistry. Miniaturized APCInebulizers that connect capillary LC with MS with flow rates inthe mLmin�1 range have been described (Nyholm, Sjoberg, &Markides, 1996; Ostman et al., 2006a). One of them that uses

microchip technology (Ostman et al., 2004, 2006a) has recentlyallowed the coupling of gas chromatography with MS (Ostmanet al., 2006b).Other authors havepreviously presented a capillaryelectrophoresis-MS coupling with a miniaturized APCI sourceby modifying a commercial source (Tanaka, Otsuka, & Terabe,2003). Another trend in MS is multimode ionization sources(Siegel et al., 1998; Gallagher et al., 2003; Syage et al., 2004;Schiewek et al., 2008); for example, APCI/APPI (ESI/APPI andESI/APCI are also commercialized). Three modes of operationare available for the APCI/APPI dual source: APPI only, APCIonly, and APPI/APCI simultaneous operation (Syage et al.,2004). It is important to note that it is possible to automaticallyswitch between bothmodes during the chromatographic analysis.The main goal is to broaden the range of compounds that can beanalyzed without the need to change the source. An unexpectedresult is that the simultaneous use of APCI/APPI does notgenerally correspond to the sum of the signals of the individualsources (Syage et al., 2004).

C. APPI Ionization

1. Description of the APPI Ion Source

Atmospheric pressure photoionization (APPI) was presented byRobb, Covey, and Bruins (2000) and Syage, Evans, and Hanold(2000) as a newLC/MS interface. TheAPPI source design is veryclose to that of the APCI source (see Fig. 1). In both cases, thesolution that contains the analytes is first vaporized in the heatednebulizer. In the APPI source, the needle that produces a coronadischarge is replaced with a UV lamp (typically a kryptondischarge lamp) that emits 10.03 and 10.64 eV photons at the exitof the probe to produce ions in the gas phase (Robb, Covey, &Bruins, 2000).

2. APPI Formation of Ions

The formation of ions by APPI shares some similarities withAPCI: for example,MHþ andMþ. are common ions formed in thepositive ion mode by both techniques and some of the gas-phasereactions that explain the presence of these ions are similar(compare Tables 1 and 3). Recent reviews that provide acomprehensive picture of the ionization mechanisms are available(Raffaelli & Saba, 2003; Robb&Blades, 2008;Marchi, Rudaz, &Veuthey, 2009). Briefly, the photons emitted by the UV lampinteract with the molecules in the vapors of the nebulizing gas,

TABLE 3. Ionization mechanisms in APPI (þ)/APPI (�)



solvent, and analyte molecules (S or M) to produce electronicallyexcited species in the gas-phase.These excited species can directlylose an electron to form odd-electron cations (Mþ.) if theirionization energies (IE) are below the photon energies deliveredbythe UV lamp (10.03 and 10.64 eV)—as depicted in Table 3(reaction 13). Krypton discharge lamps are particularly suitable toionize selectively the organic analytemolecules among the solventmolecules and other gas, because the source gases (nitrogen,oxygen) and some of the most common solvents (in particular, thesolvents used for reversed phase LC: water, methanol, andacetonitrile) have higher IEs than 10.03 or 10.64 eV (see Table 2).These solvents are consequently not photoionizable whereas alarge part of the sample molecules have IEs below 10eVand arethus photoionizable. The normal-phase solvents (hexane, iso-octane, tetrahydrofuran, toluene. . .) possess IEs below10.6 eVandcan be directly ionized by the photons emitted by the Kr lamp. Inthis case, direct ionization of the analyte does not occur efficiently.Thus, an additional substance called a dopant (D) is generallyadded to enhance the ionizationyield of the analyte, by acting as anintermediary between the photons and the analyte either by chargeexchange (Table 3, reactions 14 and 15) or by proton transfer(Table 3, reaction 16). To be photoionized, the substance selectedas a dopant must possess an IE lower than the photon energyemitted by the lamp (IE< 10 eV). Acetone, toluene, and anisoleare the most commonly used dopants with Kr discharge lamps(Kauppila et al., 2002;Kauppila, Kostiainen,&Bruins, 2004). Thecharge-exchange reaction can occur (Table 3, reaction 15) if the IEofM is lower than that of D. The proton-transfer reaction (Table 3,reactions 16) will take place if the PA of M is higher than that of[D�H].. It follows that a proton-transfer reaction is not efficientfor low-PA compounds, and that charge-exchange will proceedmore favorably if these compounds have a low IE. If the PA of thesolvent S is lower than that of [D�H]., S cannot react with Dþ.

according to Equation (17) as a single molecule (n¼ 1). However,a solvent cluster Sn can react withD

þ. if the PAof Sn is greater thanthat of [D�H]. to produce a protonated solvent cluster SnH

þ,which can transfer a proton to the analyte molecules ifPA(M)>PA(Sn)—as shown in Table 3, Equation (18).

In the negative-ion mode, the photoionization of the dopantand/or of the solvent, according to their respective IEs, releases athermal electron (Table 3, Eq. 19), and direct ionization of theanalyte M might occur by electron capture with compounds thathave a positive EA—as shown in Equation (20) (Kauppila et al.,2004). However, due to the positive EA of ever-present oxygen intheAPPI source, the formation of superoxide ionsO�

2 is expectedto be favored (Eq. 21). This latter species can initiate variousreactions: charge-exchange with the analyte M if EA(M)>EA(O2)¼ 0.451 eV (Eq. 22), proton-transfer with the analyte orthe solvent if the gas-phase acidity of these latter species is higherthan that of the HO�

2 (Eqs. 23 and 25). Similarly, proton-transferreactions can take place between the analyte and a deprotonatedsolvent molecule (Eq. 24) (Kauppila et al., 2004).

In addition to the ionization mechanisms described above,some ions (e.g., MNaþ in the positive-ionization mode) can bedelivered by thermospray ionization, a process by which ionsalready present in solution are released into the gas-phase bythermal vaporization (Delobel et al., 2003; Turnipseed et al.,2005). The contribution of this mechanism to the overallionization process can be estimated through the remaining ionsby turning off the UV lamp. This experiment is equivalent to the‘‘no-discharge’’ APCI ionization mode.

3. Factors That Influence the Performance of APPI

As seen above, the ionization pathways depend on the PAs, IEs,and EAs of the various compounds involved (solvent, analyte,and dopant), and several ionization processes can take placesimultaneously. In the positive-ion mode, compounds with lowIE and/or high PA can give intense signals. If they are present in amixture, then high-PA species are ionized preferentially overlow-IE ones (Robb, Covey, & Bruins, 2000). In the negative-ionmode, the ionization of acidic compounds or thosewith a highEAwill be favored (Kauppila et al., 2004). The solvent and thedopant, both play a decisive role in the ionization mechanisms.Consequently, the choice of the solvent composition and that ofthe dopant have a significant influence on the ionization yields,and possibly on the selectivity in the case of analyte mixture. Forreversed-phase LC/MS experiments, thewater/methanolmixturewas often found to be better thanwater/acetonitrile (Cai&Syage,2006). An increase of the relative proportion of molecular ionsMþ.was observed for apolar (low IE) compounds in the presenceof methanol (Robb, Covey, & Bruins, 2000). In the positive-ionmode, the higher PA of acetonitrile compared to that of methanolmight explain the signal-suppression effects observed in thepresence of acetonitrile (see Table 2). Moreover, acetonitrileabsorbs the photons more efficiently than methanol to producefewer photons available for analyte ionization in both ion modes(Kostiainen & Kauppila, 2009). Normal-phase LC/MS experi-ments can be successfully implemented with non-polar solventssuch as hexane, isooctane. . . (Cai & Syage, 2006). These low-PAsolvents are readily vaporized. For low-PA compounds, theionization through charge exchange can be enhanced efficientlywith toluene as dopant (Kauppila et al., 2002). For the analysis ofpolar compounds, acetone seems to be the most-appropriatedopant that leads to proton transfers towards higher PA analytes(Mol, de Jong, & Somsen, 2005). In the negative-ionmode, weakacids (formic acid, acetic acid. . .) are not recommended becausethey might affect the deprotonation of the analytes or neutralizethe superoxide ions. Halogenated solvents (chloroform,dichloromethane. . .) scavenge electrons, and by dissociativeelectron capture, produce X� (Cl�, Br�, I�, F�) for anion-attachment (Song et al., 2007). Flow rate (typically about 100–200mL/min) is another factor that can have a great influence.Too-high flow rates can lower the ionization efficiency (Robb &Blades, 2005).

Currently, only two APPI sources are commerciallyavailable: Photospray1 and Photomate1, which can differ intheir geometry (in-line or orthogonal, according to the model)and by their ability, or not, to accept a dopant directly.Differencesin the behavior of the two sources have been reported due to thefact that the UV lamps employed are not identical and that adifferent set of voltages is applied on the ion pathway (Robb &Blades, 2008).

IV. APCI AND APPI FOR SYNTHETICPOLYMER ANALYSIS

Since themid-1990s, APCI for the analysis of synthetic polymershas been the subject of about 20 articles. Direct analysis was farless described than LC/MS. APPI for polymer analysis was evenless described: to our knowledge, only two articles have reportedit, both with direct infusion. Table 4 collects these studies. Giventhe numerous advantages of APCI and APPI for polymer

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analysis, the relatively small number of articles in this field andthe narrow range of studied polymers are surprising. In thisreview article, the advantages and drawbacks of polymer analysiswithAPCI andAPPIwill be described and illustratedwith relatedpublished works. Direct infusion and LC/MS with APCI, thendirect infusion with APPI will be addressed.

A. APCI for Direct Analysis

Four articles dealt with APCI direct analysis of syntheticpolymers (Pattanaargsorn et al., 1995; Huang & Rood, 1999;Schroder & Fytianos, 1999; Bernabe-Zafon, Simo-Alfonso, &Ramis-Ramos, 2006). All of them were studies of alcoholethoxylates, alcohol propoxylates, their derivatives, or theirmetabolites.

1. Individual Detection of Oligomers in SimpleMass Spectra

The ability to detect individually each component of a mixturecorresponds to a major feature shared by all mass spectrometrytechniques. In the case of polymers, which are a mixture ofoligomers with different sizes and possibly different composi-tions, this ability is a rare advantage, because more classicaltechniques (SEC, NMR. . .) provide only an average detection.With APCI, this feature is reinforced by the relative simplicity ofthe spectra. Indeed, unlike ESI, APCI generates only singlycharged ions. Thus, each oligomer is detected through only onepeak (provided that only one kind of adduct is formed).Moreover, unlikeMALDI, the detection of low-mass compoundsis not hindered by matrix peaks. These strengths of APCI massspectrometry are illustrated here with two articles (Pattanaarg-sorn et al., 1995; Schroder & Fytianos, 1999). Schroder andFytianos used direct infusion with APCI and ESI in the positive-ion mode to detect and identify fatty alcohol ethoxylate (FAEO,CmH2mþ1(OCH2CH2)nOH), fatty alcohol propoxylate (FAPO,

CmH2mþ1(OCH2CHCH3)nOH), poly(ethylene glycol) (PEG),and poly(propylene glycol) (PPG) in waste water taken fromthe inflow and the outflow of a treatment plant (Schroder &Fytianos, 1999). After a concentration step with Solid-PhaseExtraction (SPE), a separation was performed by a selectiveelution of the analytes according to their polarity. Because of thisfirst step, each sample submitted toMS contained only onemajortype of polymer. ESI and APCI analysis showed intact molecularions (proton or ammonium adducts) with a negligible amount offragmentation. Only singly charged ions were detected in APCImass spectra whereas multiply charged ions were present in ESImass spectra. The masses and spacing between adjacent peakscan lead to the identity of the polymers. For instance, Figure 2shows a SPE-fraction eluted with a mixture of water andmethanol. Each peak corresponds to an oligomer with a differentnumber of repeat units. The spacing between two adjacent peaksis 44Da, which is the mass of one ethylene oxide unit. Then, them/z value of ions allows the supposition that both end-groups arehydroxyl. This spectrum was thus attributed to PEG, which is analcohol ethoxylate metabolite. In the same way, the identity ofPPG, FAEO, and FAPOwas established. Moreover, from theMSspectra, it was possible to monitor the differences betweeninflow and outflow, and to estimate the efficiency of thedegradation for a given polymer. Pattanaargsorn et al. (1995)used positive APCI to analyze several alkylphenol ethoxylates(APEO, CnH2nþ 1-C6H4-O(CH2CH2O)nH) with different aver-age degrees of ethoxylation, and a mixture of fatty alcoholethoxylates with different lengths of alkyl base. For all samples,each component in the mixture could be individually detected asa protonated species. Thus, on the spectrum of a nonylphenolethoxylate (Fig. 3a), each peak corresponds to a chain with adifferent number of ethylene oxide (EO) units. Moreover, anunexpected additional distribution was detected and attributed toa poly(ethylene glycol) contaminant. In the case of fatty alcoholethoxylates, the sample was more complex because—on top ofthe different numbers of EO units—three different lengths of

TABLE 4. Summary of the studies using APCI or APPI sources for synthetic polymer analysis



alkyl chain also co-existed. However, in this particular case,again each oligomer could be easily detected (see Fig. 3b). Thepoly(ethylene glycol) contaminant was also detected in thisspectrum; it increased to four the number of co-existingdistributions.

To conclude, because of the ability to detect individuallyeach oligomer in simple mass spectra, APCI-MS allows therapid identification of a polymer and the distinction of severalpolymers in a complex mixture.

2. Average Molecular Masses and Relative Abundances

The ability of APCI-MS to detect the oligomers individuallythrough simple mass spectra makes virtually easy the determi-nation of the average molecular mass of each polymer presentin a blend, as well as the relative abundances of these polymers.This unique feature of mass spectrometry would constitute aconsiderable advantage over the other analytical methods if therewere not so many pitfalls. The response factor (related to theefficiency of the formation of gaseous ions, transmission anddetection) can vary according to the species, their masses and theexperimental conditions. So, erroneous results can be obtained ifaverage molecular masses and relatives abundances are calcu-latedwithout care. In the previous example (Pattanaargsorn et al.,1995), the relative intensities of the oligomers within eachdistribution were reproducible, and were independent of thecorona-discharge voltage and cone voltage. According to theauthors, this result indicated that no fragmentation occurred. Itwas also assumed that all oligomers were formed, transmittedand detected with equal sensitivity, and thus that mass spectraintensities reflected the true oligomer abundances. From theseintensities, averagemolecularmassesMn (and resulting polymer-ization degrees DPn) were calculated. Moreover, Selected IonMonitoring (SIM; in which only a few selected masses arescanned) was used to determine the proportions of the differentpolymers in the mixture. It is noteworthy that the validity of theassumption that response factors are similar whatever the chainlength and end-group was not checked, and that the obtainedvalues were not verified by comparison with results from othermethods.

The hypothesis that response factors are equivalent what-ever the chain length was recently submitted to an experiment(Bernabe-Zafon, Simo-Alfonso, & Ramis-Ramos, 2006). Theseauthors used monodisperse standards of fatty alcohol ethoxylate(with 0–7 ethylene oxide units and 10–18 carbons in the alkylchain) to study the differences in response factors (particularlythe gaseous ion formation step) and to build a model. They alsocompared ESI and APCI results. The sensitivity was lower withAPCI, but the signal-to-noise ratio remained the same. WithAPCI, all the standards showed a loss of 44Da, which wasattributed to the neutral loss of an ethylene oxide unit (theintensity of the fragment peak was 10% of the precursor). Such afragmentation occurred only to in a minor extent (less than 1%)with ESI. With both ionization techniques, in water/acetonitrileand water/methanol acid buffers, oligomers were detected asproton and sodium adducts. In both cases, the sensitivitydecreased irregularly when the number of ethylene oxide unitsand the alkyl chain length decreased, and the non-ethoxylatedoligomers gave a negligible signal. This result showed thatthe average molecular masses determined with APCI can beoverestimated if no correction is made. Determination of average

FIGURE 2. APCI-MS (þ) spectrum of a SPE-fraction of waste water.

Major peaks have been attributed to ammonium adducts of PEG. ATSQ

triple quadrupole mass spectrometer (Finnigan MAT, San Jose, CA)

equipped with an APCI source was used. Solvent was methanol/water

30:70 v/v containing 0.05M ammonium acetate. Flow rate was 0.6mL/

min. Vaporizer temperature was 4008C, capillary temperature was

2008C, corona discharge current was 4 mA. Reprinted with permission

from Schroder & Fytianos � 1999 Friedr. Vieweg & Sohn Verlagsge-

sellschaft mbH.

FIGURE 3. APCI-MS (þ) spectra of a nonylphenol ethoxylate (a) and amixture of alcohol ethoxylates (b). 1mg/mL analyte in acetonitrile–

water 60:40 v/v samplewas injected via a 10 mL injection loop into a VG

Trio 2000 triple quadrupole mass spectrometer (Fisons Instruments,

Manchester, UK) equipped with an APCI source. Source and probe

temperatures were both set at 1208C. APCI was operated at a corona

discharge voltage of 2.5 kVand at a cone voltage of 30V. The flow rate

was 0.4mL/min. Reprinted with permission fromPattanaargsorn et al.�1995 Royal Society of Chemistry.

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molecular masses should be performed cautiously, and itsreliability should be checked for each new case.

Another study can provide some information about thecapability of APCI-MS to determine relative abundances of co-existing polymers in a mixture. Huang and Rood (1999) studiedalcohol ethoxylate and its reactions to yield alkyl-capped alcoholethoxylate and alcohol ethoxycarboxylate. The goal of the studywas to characterize the distributions and to determine theproportions of reagents and products to estimate yields andconversions of the reaction. They compared gas chromatographycoupled to MS (GC/MS), which is the conventional method forthis kind of study, with FAB, MALDI, ESI, and APCI. FAB andMALDI were quickly dismissed because of mass-discriminationeffects due to the underestimation of the most-hydrophobiccompounds. For ESI, it was found that an increase of the capillarytemperature or skimmer voltage was necessary to remove wateradducts, but induced different shifts towards the low massesaccording to the nature of the polymer. This phenomenonprevents the quantitative comparison of the different oligomerdistributions. The focus of that study was thus the comparisonbetweenGC/MS andAPCI-MS. This comparisonwas performedby analyzing the unreacted polymer and the reaction mixtures(alkylation and carboxylation) with GC/MS (using chemicalionization with CH4) and APCI-MS. In both cases, all thecomponents could be detected as molecular ions, but the APCI-MS spectra were simpler because only protonated species wereformed whereas protonated and deprotonated species were bothformed with GC/MS. Moreover, thermal decomposition orfragmentation was observed for higher GC retention times, andthe highest molecular mass observed (742Da) was significantlylower than with APCI-MS (950Da). The most importantdifference between GC/MS and APCI-MS was that the GC/MSresponse factors for each component from reacted/unreactedpolymers were different (to produce apparently uneven oligo-meric distributions), whereas the oligomeric distributionsdetected by APCI were uniform. This last feature allowed, onlyin the case of APCI-MS, the determination of the proportion ofeach kind of polymer. The calculation of product yields andconversions could thus be performed. This method was validatedbecause these results, and the data obtained with NMR analysis,were in a good agreement. In addition, a noteworthy differencebetween GC/MS and APCI-MS was the time of analysis. TheGC/MS analysis requires the silylation of the analytes, andincludes a separation step, which is time consuming (a 2 hranalysis). On the other hand, only 5min were necessary toperform the directAPCI-MSanalysis. The only advantage ofGC/MS over APCI-MS was the ability to distinguish isobaric ionsdue to the GC separation step. This study showed that, undercertain conditions, APCI-MS can give a reliable image of anoligomer distribution, and can be used to determine theproportion of polymers in a blend (Huang & Rood, 1999).However, this feature depends on the nature of the differentpolymers. As for the determination of average molecular masses,the reliability of this measurement should be assessed for eachnew case.

B. APCI Interface for LC/MS Analysis

The number of articles that deal with LC/APCI-MS is muchhigher than that deal with direct analysis (Table 4). However therange of studied polymers remains limited. Alcohol ethoxylates

and various polymers of ethylene oxide or propylene oxidewith different end-groups are still the most-studied polymers.Other studied polymers are cyclic poly(alkylene terephtalates),poly(tetrahydrofuran), polymers and copolymers of siloxanes,epoxy resins, linear alkylbenzene sulfonates, and a copolymer ofe-caprolactone and ethylene oxide.

1. A Versatile LC/MS Interface

Solvents suitable for the ESI process must permit ion formationin solution. In addition, the desolvation/nebulization phenom-enon requires solvents with an appropriate surface tension,viscosity, and heat of vaporization. A mixture of polar solventssuch as water/methanol is optimal for the ESI process. As aconsequence, ESI is fully compatible with RPLC, but thecoupling with NPLC or SEC in low-polarity solvents can bechallenging or simply impossible (Voyksner, 1997). In contrast,APCI can work whatever the polarity of the solvent. APCI can bedirectly coupled with NPLC and SEC, for which non-polarmobile phases such as hydrocarbons or chlorinated solvents areused. This versatility was well-shown in a recent study(Desmazieres et al., 2008). The authors probed the potentialityof RPLC/APCI-MS, NPLC/APCI-MS, and SEC/APCI-MS byanalyzing different kinds of polymers [fatty alcohol ethoxylates,poly(tetrahydrofuran), polymers and copolymers of siloxanes].For instance, different methods of separation for fatty alcoholethoxylate were described. First, a mixture of fatty alcoholethoxylates was analyzedwith RPLC coupled toAPCI-MS in thepositive-ion mode. The mobile phase was methanol. In this case,polymers were separated according to the length of their alkylchain. Figure 4, top, shows the detection of this separation withAPCI-MS. The ability of APCI-MS to be coupled with normal-phase LC was shown with the analysis of another fatty alcoholethoxylate sample. The mobile phase was a mixture of hexane/dichloromethane/methanol (from 92/4/4 to 76/12/12 v/v/v).Here, the separation was made according to the number ofethylene oxide units. Finally, SEC with dichloromethane as themobile phase allowed a separation according to the hydro-dynamic volume and was successfully coupled to APCI-MS inthe negative-ionmode. ForNPLCandSEC,ESI ionizationwouldhave failed because of the low polarity of the solvent. On top of itsversatility, APCI can tolerate higher flow rates than ESI. Thisfeaturemakes the coupling easier. For instance, Fuchslueger et al.compared LC/ESI-MS and LC/APCI-MS for the analysis ofepoxy resins. Whereas APCI could be directly connected to thecolumn outlet, ESI required a tee to introduce a buffer solution,followed by another tee to split and thus reduce the flow(Fuchslueger et al., 1999).

2. Identification of Compounds in Chromatographic Peaks

One of the most obvious advantages of APCI-MS detection is toallow the unambiguous identification of the compounds in thechromatographic peaks. Indeed, whereas classical detectors onlyindicate the presence of an unidentified compound, MS givesmass information that can lead to the unambiguous identificationof the eluted species. As one among many other examples,Scullion et al. (1996) separated the components of amixture of anoctylphenol ethoxylate and a linear alkylbenzene sulfonate.CouplingwithAPCI-MSallowed the unambiguous identificationof compounds in the representative peaks. Indeed, oligomersof linear alkylbenzene sulfonates (LAS) were detected as



FIGURE 4. RPLC/APCI-MS (þ) chromatogram of amixture of alcohol ethoxylates (top). Mass spectra of

selected fractionsA,B,C, andD (middle) and APCI-MS (þ) direct analysis (bottom). AC18 bonded silica

column (Waters Symmetry, 150� 3.9mm ID, 4mm particle diameter) was used with methanol as mobile

phase. Flow rate: 0.8mL/min, 5mL injected (100 ppm). Spectra were recorded using a Q-Star Pulsar

quadrupole time-of-flightmass spectrometer (AppliedBiosystems, Foster City, CA) equippedwith anAPCI

source. The heater temperature was 3508C, needle current 2–3mA. Nebulizing gas was N2 (80 psi).

Reprinted with permission from Desmazieres et al. (2008). � 2008 American Chemical Society.

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[Mþ 2Na]þ in the positive-ion mode and as [M�H]� in thenegative-ion mode, and oligomers of octylphenol ethoxylatewere detected as [MþH]þ, [MþNa]þ, [Mþ 2Na]þ, and[Mþ 3Na]þ, in the positive-ion mode. Another example is theseparation of linear and cyclic poly(tetrahydrofuran) (pTHF)with liquid chromatography (Mengerink et al., 2003). Under thecritical conditions, it was possible to have retention timesdependant on functional groups and independent of polymer-ization degree, and thus only two peaks corresponding to linearand cyclic polymer. The LC/APCI MS coupling permitted theidentification of those two peaks and themonitoring of the qualityof the separation. Then LC-RI or LC-LS could be used forquantitative purpose.

3. Increasing LC Resolution

The ability to identify a mixture of species in a chromatographiceluent is especially useful when LC fails to separate somecompounds. Recently RPLC/APCI-MS was used to analyze ablock copolymer of methylsiloxane (–OSiHCH3–) and dime-thylsiloxanes (–OSi(CH3)2–) (Desmazieres et al., 2008). Eachchromatographic peak contained overlapping oligomers with thesame number of methyl groups but with different methyl/dimethyl ratios. Whereas a classical detector would fail todistinguish the different co-eluting oligomers,APCI-MS allowedthe individual identification of these compounds because of theirdistinct molecular masses. Another example can be found in astudy of the chromatographic behavior of fatty alcoholethoxylates on various columns (Jandera, Holcapek, & Theodor-idis, 1998). Positive-ion APCI-MS detection was combined tothe different chromatographic systems. Oligomers were detectedasMHþ ions with little fragmentation. First, the FAEO polymerswere separated in the normal-phase mode according to thenumber of ethylene oxide units. The impact of the alkyl chainlength on retention is low, and all the chains with the samenumber of EO units, but with different alkyl chain lengths, are inthe same peak if the total ion current (TIC) is used to record thechromatogram (Fig. 5A). In this case, a chromatogram can bereconstructed by considering only the ion current of an individualoligomer with a given alkyl chain length (reconstructed ioncurrent, RIC). Figure 5B shows the reconstructed chromatogramfor all polymers with a C16 alkyl chain, whereas Figure 5C showsthe C18 oligomers. In this way, it was possible to observe theeffect of the alkyl chain length on the retention (a higher retentionfor shorter alkyl chains). On the other hand, the reversed-phasemode permitted the separation of the polymer according to thelength of the alkyl chain with a low impact of the number ofethylene oxide units. By using a high concentration ofacetonitrile in the mobile phase, it was possible to increase theethylene oxide selectivity. However, in the meantime, themethylene selectivity decreased and the chromatographic peaksoverlapped. In this case again, it was possible to reconstruct achromatogram in which the retention time of each kind ofoligomer can be determined. In the sameway, Jandera, Holcapek,andKolarova (2000) studied the retentionmechanisms of variousblock copolymers of ethylene oxide and propylene oxide in LCunder critical conditions (in which the separation according toone type of repeat unit is suppressed). On-line coupling withpositive-ion APCI-MS detected oligomers as MHþ ions withlittle fragmentation, then enabled the unambiguous determina-tion of the individual oligomers and their monitoring. In some

cases, that strategy was the only way to deconvolute overlappedpeaks. These examples showed that APCI is not only analternative detector, useful when more classical ones fail, butalso resolves overlapping chromatographic peaks.

4. Simplification of the Mass Spectra

Another major advantage of LC/APCI lies in the fact that massspectra, which can be easily interpreted, are obtained. Figure 4

FIGURE 5. NPLC/APCI-MS of alcohol ethoxylate. The separation was

performed on a Separon SGX NH2 column (7mm, 150� 3mm ID) with

acetonitrile–water–dichloromethane (69.3:0.7:30) as the mobile phase.

Flow-rate: 1mL/min, column temperature: 408C.Themass spectrometer

was a VG Platform quadrupole mass spectrometer (Micromass,

Manchester, UK) equipped with an APCI source. A potential of

3.05 kV was applied on the discharge needle. The temperature was held

at 5008C in the APCI probe and at 908C in the ion source. Nitrogen was

used as the drying, sheath, and nebulizing gas.Mild ionization conditions

with cone voltage of 10V were selected to yield mass spectra with little

fragmentation. The numbers of peaks agree with the numbers of the

oxyethylene units in the oligomers. A: TIC chromatogram. B:Reconstructed chromatogram of MHþ ions of C16 alcohol ethoxylates.

C: Reconstructed chromatogram of MHþ ions of C18 alcohol

ethoxylates. Reprinted from Jandera et al., � 1998, with permission

from Elsevier.



(bottom) shows the direct-infusion APCI-MS spectrum of theabove-mentionedmixture of alcohol ethoxylates (Desmazieres etal., 2008). Without prior separation, all the oligomers weredetected in the same spectrum. As seen in the expanded region,the spectrum contains a high density of peaks. Some isotopicpatterns can overlap tomake difficult the assignments of ions andtheir relative abundances. After the RPLC separation, a spectrumwith only the distribution of ethylene oxide units can be obtainedfor each chromatographic peak (Fig. 4, middle). These spectraaremuch simpler: no overlapping of isotopic patterns (or isobaricions) is observed. Thus, each peak can be unambiguouslyassigned, and its intensity can be quickly determined.

5. Detection of Low-Abundance Compounds

By reducing the number of analytes simultaneously detected byMS, the preliminary separation step not only simplifies thespectra, but also helps prevent spectral-suppression effects. Thisseparation step can be very useful to detect some low-abundancecompounds in a complex mixture. In a previously mentionedarticle, Schroder and Fytianos (1999) could detect and identifythe major compounds in different extracts fromwaste water withdirect-infusion APCI-MS. However, they failed to detectnonylphenolethoxylate because of its low abundance in acomplex matrix. In this case, the coupling of MS with RPLCwas the only way to confirm the presence of this polymer.Another striking example of the strength of LC/APCI-MS todetect minor compounds has been recently reported (Schneider,Sablier, & Desmazieres, 2008). The authors showed theadvantages of LC/APCI-MS over pyrolysis-GC/MS, ESI-MS,MALDI-MS, FT-IR, and NMR to analyze an unknownsample of PDMS. In this study, APCI was suitable for a LCcoupling because of the mobile phase (acetonitrile/acetone).This technique detected and identified linear trimethyl-ended polydimethylsiloxane with masses up to 5,300Da(fragmentations became dominant above 3,000Da). In additionto this main series, low-intensity hydrogen-, hydroxyl-, dihy-droxy-terminated linear polydimethylsiloxanes and cyclic poly-dimethylsiloxanes were also detected with relative abundancesthat ranged from 0.1% to 5%. These APCI results were the mostcomplete obtained in the course of this study. Indeed, MALDI-TOF spectra displayed the linear polymer with trimethyl end-groups (with degrees of polymerization compatible with thoseobtained with LC/APCI-MS) and the hydrogen-terminatedpolymer, but not the cyclic polymer, the hydroxyl- and thedihydroxy-terminated polymers. NMR and ESI-MS detectedonly the cyclic polymer and the main series. FT-IR alone showedthe presence of cyclic polymers. To characterize this unknownsample, the capability of LC/APCI-MS made it a powerfultechnique that provided simpler and more complete data.

6. Thermal Decomposition, Up-Front Fragmentation,and MS/MS Experiments

The APCI technique is known to be more-energetic than ESIbecause a high temperature is applied to the probe to vaporize thesample and the solvent. The heating of the probemay cause somethermal decomposition. On top of the intactmolecular ions, someunwanted fragment ions are sometimes detected due todegradation of the thermally most unstable compounds. The factthat these ions remain even if only small voltage differences are

applied between the elements in the ion transport region of themass spectrometer can be a good indication of this phenomenon.In contrast, fragment ions can also be produced by CID in theinterface region between the source and the mass analyzer (up-front CID), or in a collision cell (MS/MS) in a controlledmanner.Such fragmentations can be used to confirm the structure of apolymer. Thus, Combs, Johnson, and Szekely-Klepser (2005)used LC/MS and LC/MS/MS to characterize polyethoxylateswith various end-groups (PEG, PEG methacrylate, PEG laurate,PEG dimethyl ether, PEG lauryl alcohol, PEG dimethacrylate,PEG diacrylate, octylphenol ethoxylate). In that study, APCI andESI were compared. Both ionization techniques gave a strongsignal of intact protonated molecules (or ammonium adducts).Doubly and singly charged ions were observed in ESI, whereasonly singly charged ions were formed with APCI. After thedetermination of the oligomer distribution with a wide scan, theauthors tried up-front fragmentation andMS/MS in an ion trap toidentify the end-groups. Up-front fragmentation could be doneon only one ion at a time thanks to the previous chromatographicseparation. Fragmentation spectra from APCI and ESI weresometimes different, but for each polymer, the same intensefragment ion characteristic of the end-group was obtained. Up-front fragmentation was preferred over MS/MS because the iontrap low-mass cut-off limited the MS/MS to oligomers with aheavy end-group. Another example of the utility of fragmenta-tion experiments can be found in the previouslymentioned articleby Schroder and Fytianos (1999). In that study, comparison ofCID experiments with MS/MS spectra of a standard was used toconfirm the identity of unknown polymers such as FAEO, forwhich single-stage MS only was insufficient. Moreover, it ispossible to take advantage of the up-front fragmentation to tracktargeted compounds. Thus, Barcelo’s group published a methodto detect, identify, and quantify anionic and non-ionic pollutantsat trace levels in sewage sludge, tannery wastewaters, and textilewastewaters (Castillo, Ventura, & Barcelo, 1999; Castillo et al.,1999; Petrovic & Barcelo, 2000). The first step involved SPE:analyteswere pre-concentrated and extracted in specific fractionsaccording to their polarities and functional groups. Each fractionwas analyzed with LC/MS. Ion-pair or RPLC/ESI-MS in thenegative-ion mode was used to analyze polar or anioniccompounds (such as linear alkyl sulfonates). Less-polar com-pounds (including the following polymers: fatty alcoholethoxylates, alkylphenolethoxylates, polyethylene glycol) wereanalyzed with RPLC/APCI-MS in the positive-ion mode. Thepolymer could be identified by comparing retention times andfull-scan spectra with those of authentic standards. Preliminaryexperiments, in which non-ionic polymers of each kind weredirectly analyzed with APCI-MS, showed MHþ molecularions (and sometimes MNaþ, MKþ, and MNHþ

4 ) and severalseries of intense fragment ions. Figure 6 displays an exampleof such a spectrum. Some of those fragment ions were commonto FAEO, APEO, and PEG, whereas others were characteristicof a type of polymer. Thus, SIM could be used to monitor areduced number of diagnostic fragment ions after LCseparation to allow the detection and identification of the threetypes of polymers. It is noteworthy that SIM limits of detectionwere up to 13-times better than full-scan acquisition mode. Inthese articles, the authors pointed out the advantage of LC/MSover GC/MS to determine pollutants in complex matrixes: theclean-up procedure is much simpler, and no derivatization step isneeded with LC/APCI MS. Moreover, GC/MS does not detect

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low-volatility compounds, and only partial information wasobtained.

7. Ideal for Low Masses, more Problematic forHigh Masses?

APCI-MS is usually employed for the analysis of low-masscompounds. Indeed, because of the absence of matrix peaks,APCI is a good alternative toMALDI for species<1,000Da (notto mention the easier LC coupling). For example, the previouslymentioned studies of Barcelo’s group dealt with the analysis ofvery low-mass polymers (with masses down to 200Da). Theanalysis of alkylamine ethoxylates and alcohol ethoxylates, withstandards with masses down to 250Da in environmental water(Krogh et al., 2002), constitutes another similar example. On theother hand, few studies have referred to relatively high-masspolymers. It is commonly believed that thermal decompositionprevents the analysis of such species. Desmazieres et al. (2008)tried to analyze with LC/APCI-MS and SEC/APCI-MS differentkinds of polymers (alcohol ethoxylates, polytetrahydrofuran,polydimethylsiloxanes, and copolymers of methyl- anddimethyl-siloxanes) with molecular weights up to 5,000Da.The SEC/APCI-MS analysis in the negative-ion mode wasimplemented successfully with different fatty alcohol ethox-ylates. On top of the intact MCl� ions, thermal decompositionswere observed for masses >1,500Da. The extent of thesedecompositions increased with the molecular mass of theoligomers, and the chains with masses >2,500Da could not bedetected as intact molecules. Modification of the temperature orpressure in the source did not improve these results. On the otherhand, the analysis of a polytetrahydrofuran and a polydimethyl-siloxane with RPLC/APCI-MS in the positive-ion mode led to avery good separation of the various chains, and intact oligomers

were detected up to, respectively, 3,000 and 4,500Da (Fig. 7).These experiments showed that the upper-mass limit for thedetection of an oligomer can be relatively high, but depends onthe nature of the polymer and on the mobile-phase composition(Desmazieres et al., 2008).

8. Detection of Species Those Are Difficult toDetect with ESI

One major advantage of APCI-MS lies in its ability to detectcompounds that are difficult or impossible to detectwithESI-MS,particularly hydrophobic compounds. The first reports on the useof LC/APCI-MS for polymer analysis dealt with cyclic poly-(ethylene terephthalate) and poly(butylene terephthalate)(Barnes et al., 1995; Harrison et al., 1997; Bryant & Semlyen,1997a,b). The hydrophobic nature of cyclic poly(alkyleneterephthalates) makes them difficult to be detected with massspectrometry.Until 1995, only the smallest oligomers (less than 4repeat units) could be detected with LC/MS methods (thermos-pray and plasmaspray). Barnes et al. (1995) detected cyclicpoly(ethylene terephthalate) (PET) with 3–7 repeat units (asMHþ ions) with RPLC/APCI-MS in the positive-ion mode. Thesensitivity was quite poor when the total ion current (TIC) wasthe detection mode, but improved when only a few selected ionswere recorded (SIM mode). Less than 1 injected microgram ofpolymer was sufficient, making this method as sensitive as UVspectroscopy and more sensitive than thermospray-MS. It isnoteworthy that fragmentations were sometimes observed.Moreover, a minor series was also detected, and was assignedto oligomers in which the monoethyleneglycol was replaced by adiethyleneglycol. Such cyclic poly(alkylene terephthalate) werealso detected with LC/APCI-MS in the positive-ion mode byBryan and Semlyen. Two articles were published: one on

FIGURE 6. APCI-MS (þ) spectrum of an alcohol ethoxylate (C10EO3). Arrows indicate the molecular

ions. Squares, circles and stars indicate fragment ions. The spectrum was recorded with a VG Platform

quadrupole mass spectrometer (Micromass) equipped with an APCI source. Twenty microliters of

10mg/mLmethanolic solution of polymerwere injected. Source and probe temperatureswere set at 150 and

4008C respectively, corona discharge voltage was maintained at 3 kVand the cone voltage was set at 30V.

Nitrogenwas used as nebulizing and drying gas at a low rate of 10 and 300 L/hr, respectively. Reprinted from

Castillo et al., � 1999, with permission from Elsevier.



poly(ethylene terephthalate) (Bryant & Semlyen, 1997a), theother on poly(butylene terephthalate) (PBT) (Bryant & Semlyen,1997b). Both articles emphasized the synthesis of cyclicoligomers. Products were characterized with a variety ofmethods: SEC, RPLC, NMR1H, FAB-MS, RPLC-APCI-MS,and MS/MS. While SEC and RPLC (with refractive index andUV detector, respectively) showed oligomers with 3–13 PETrepeat units and 2–9PBTrepeat units, FAB-MScould detect only3–7 and 2–6 repeat units, and RPLC/APCI-MS (SIM scanning)showed 3–9 and 2–9 repeat units. FAB and RPLC/APCI-MSboth detected the same minor series as the one described byBarnes et al. (1995). Moreover, tandem mass spectrometryexperiments confirmed the nature of PBT ions by showing thesame fragment ions as those detected by Montaudo, Puglisi, andSamperi (1993) with pyrolysis-CI-MS. Finally, Harrison et al.(1997) also characterized cyclic poly(ethylene terephthalate).Field desorption-MS, RPLC/APCI-MS, and MS/MS were used.FD-MS and RPLC/APCI-MS in the positive-ion mode bothdetected oligomers with 3–8 repeat units. The advantage of SIMover TIC detection in terms of sensitivity was confirmed. LC/

APCI-MS/MS showed in each case the loss of a neutral cyclictrimer.

If APCI detection is more efficient than ESI for somecompounds, then the opposite can also be true. Van Leeuwen etal. used LC/MS to characterize a block copolymer consisting ofmethoxy poly(ethylene oxide) (mPEO) and a e-caprolactonesegment (pCL) (vanLeeuwen et al., 2007). ESI andAPCI, each inthe negative- and positive-ionmodes were compared. The resultspresented in that article illustrated clearly that the two methodsare complementary. In that study, the samples were verycomplex: on top of the copolymer, other polymeric species:mPEO,mPEO-pCLn, pCLn, and cyclic pCLn could co-exist. In asecond even-more complex sample, the copolymer was function-alizedwith lactic acid (LA).As a result, all the compounds namedabove and all their LA derivatives could co-exist. Before MSanalysis, the polymer was separated with reversed-phase HPLC.Figure 8A–D is the chromatograms of non-functionalized andfunctionalized copolymer monitored with the Total Ion Currentin APCI and ESI in the negative-ion mode. pCLn, cyclic pCLn,and pCLn-LAwere clearly detected with ESI and APCI. On the

FIGURE 7. RPLC/APCI-MS (þ) separation of a poly(dimethylsiloxane). Two C18 bonded silica columns

(Merck Lichrospher, 250� 4mm ID, 5mm particle diameter) were used with a acetonitrile/acetone (66:34)

mixture as mobile phase, flow rate 0.8mL/min. Temperature programming 25–808C, 18C/min. Spectra

were recorded with a Q-Star Pulsar quadrupole time-of-flight mass spectrometer (Applied Biosystems)

equipped with an APCI source. The source heater temperature was 3758C, needle current 2–3mA.Nebulizing gas was N2 (80 psi). Reprinted with permission from Desmazieres et al. (2008). � 2008

American Chemical Society.

& TERRIER ET AL.


other hand, only the APCI spectra displayed clear signals frommPEG, mPEO-CLn, and mPEO-CLn-LA. It is noteworthy thatthe copolymer and its derivative produced very low signals,whereas they were expected to be the main components of thesamples. Figure 8E,F is the chromatograms recorded frompositive-ion ESI detection. The ionization of the copolymer ismuch more favored, but some by-products (pCLn, cyclic pCLn,pCLn-LA) are hardly, if ever, detected. Lastly, APCI in thepositive-ion mode (spectrum not shown) was less-sensitive thanpositive-ion ESI, but more suitable to detect the cyclichomopolymer. To conclude, only a combination of the variouschromatograms obtained with the different ionization techniquespermitted the demonstration of the presence of products and by-products in significant amount. Obviously, the exact ratio couldnot be determined because of the different MS responses for allthe components. It is noteworthy that the incomplete detectionfor each ionization technique simplifies the chromatogram andcounterbalances the incomplete resolution of the separation.Moreover—as seen previously—the use of selective massspectrometry detection (SIM mode) helps to reconstruct achromatogram for selected species. From the mass spectra, theauthors noticed a large diversity of species produced by theionization processes. [Mþ xNH4]

xþ and [MþNa]þ weredetected in positive-ion ESI; [MþHCOO]�, [M�H]�,[M�HþHCOONa]� in negative-ion ESI; [MþNH4]

þ,[MþH]þ in positive-ion APCI; and [MþHCOO]�, [M�H]�,[M�HþHCOONa]� in negative-ion APCI. Lastly, somefragmentation (loss of CL units) was observed for APCI in thenegative- and positive-modes, but only intact molecular ions

were detected with ESI. The complementarity showed in thisexample is particularly interesting because ESI/APCI dual-ionization sources are now commercially available.

9. Characterization of the Oligomer Distribution (Mn, Ip)

Average molar massesMn (or average degrees of polymerizationDp) and polydispersity indexes Ip can be easily deduced fromAPCI mass spectra of polymers. However, as seen in part IV.A.2,the results must be considered with care. From the analysis ofvarious alcohol ethoxylates (with RPLC/APCI-MS, NPLC/APCI-MS, and SEC/APCI-MS), a polytetrahydrofuran (withRPLC/APCI-MS), a polydimethylsiloxane (with RPLC/APCI-MS) and a co-polymer ofmethylsiloxane/dimethylsiloxane (withRPLC/APCI-MS), Desmazieres et al. (2008) calculated theaverage mass and polydispersity index of each sample andcompared the results with those obtained with MALDI and SEC.Masses of alcohol ethoxylates were very underestimated (downto 50%) with APCI-MS compared to MALDI-MS or SEC. Thisunderestimation is the result of a large extent of thermaldegradation for the heaviest chains. In the case of a mixture ofdifferent alkyl chain lengths, onlyMSmethods could provideMn

values specific to each polymer, whereas SEC gave only a globalvalue ofMn. For polytetrahydrofuran and polydimethylsiloxane,masses determined with APCI-MS were lower (80%) than thosedetermined with SEC, but higher (200%) than those determinedwith MALDI-MS. Lastly, for the copolymer of methyl- anddimethyl-siloxanes, SEC was not suitable to determine theaverage molecular weight for each kind of repeat unit. APCI-MS

FIGURE 8. RPLC/MS chromatograms (TIC) of (A,C,E) non-functionalized and (B,D,F) functionalizedpolymer recorded with (A,B) APCI(�), (C,D) ESI(�), and (E,F) ESI(þ). A C8 bonded silica column

(Macherey-Nagel, 150� 2.1mm ID) was used. The following gradient of acetonitrile (solvent B) in 20mM

aqueous ammonium formate buffer (pH3, solventA)was applied: 2min isocratic at 10%B (v/v), increase of

solvent B to 95% over 38min, held at 95% B for another 39min and then returned to 10% B within 1min,

where a 10min column equilibration is allowed. Flow rate: 0.3mL/min, 5 mL injected. Mass spectra were

recorded using an Esquire 3000 plus ion trap (Bruker, Bremen, Germany) equipped with an ESI or APCI

source. For ESI, spray voltagewas 4 kV, nebulizer gas pressurewas 40 psi, drying gas flow ratewas 9 L/min,

and drying gas temperature was 3658C. For APCI, spray voltage was 1.5 kV, corona discharge current was2.5–3 mA, nebulizer gas pressure was 50 psi, nebulizer gas temperature was 3758C, drying gas flow rate

was 4 L/min, and drying gas temperature was 3508C. Reprinted with permission from Van Leeuwen et al.

� 2007 John Wiley & Sons, Ltd.



and MALDI gave similar results. When comparing polydisper-sity indexes for all polymers, APCI-MS values were higher thanMALDI-MS values, and lower than SEC values (Desmaziereset al., 2008).

10. Quantification

As previously stated, in the case of polymer blends, the relativeabundance of each polymer can potentially be estimatedfrom APCI mass spectra (Huang & Rood, 1999). Similarly,Desmazieres et al. (2008) showed, in the case of a blend of fattyalcohol ethoxylates, that, by integrating the chromatographicpeak areas from the TIC, the RPLC/APCI-MS analysisdetermined relative proportions of polymers for the differentlengths of alkyl chains that were close to the expected ones. Inthose exceptional cases for which the polymers have very-similarstructures, the ionization efficiency seems to be independent ofthe nature of the polymer. Unfortunately, in most cases therelative intensities do not reflect the actual relative abundances.Thus, in the previously mentioned article of Schneider et al.,FT-IR and NMR showed that cyclic polymers were present inlarge proportion (80%) in the polymer mixture. However, thecorresponding LC/APCI-MS signal was very minor comparedto the methyl-terminated polymer (Schneider, Sablier, &Desmazieres, 2008). Similarly, the analyses by van Leeuwen etal. (2007) of a complex mixture displayed totally differentabundance ratios with different ionization methods (ESI andAPCI in positive- and negative-ion modes); these resultshighlight the lack of correlation between actual abundance andMS intensity. Therefore, the problem of relative quantificationmust be addressed with care on an individual basis. This problemis a well-known drawback shared with all mass spectrometrytechniques.

On the other hand, with standards, it is possible to determinethe absolute concentration of a polymer. Thus, in the previouslymentioned articles of Barcelo’s group (Castillo, Ventura, &Barcelo, 1999; Castillo et al., 1999; Petrovic & Barcelo, 2000),quantification of the detected polymers was performed with SIMor TIC chromatograms with an external calibration. It was notedthat the quantification of lower-mass polymers could be under-estimated because the MS response rapidly decreases as thenumber of ethoxy groups in the polymer decreases.

C. APPI for Direct Analysis

As mentioned previously, the use of APPI is even less-describedthan APCI for polymer analysis. To our knowledge, only twoarticles from the same group have been published (Keki et al.,2008a,b). The reported results are very promising because theyshow the ability ofAPPI to analyze somepolymers that are hardlyionizable byMALDI or ESI. APPI provides promising results fornon-polar polymers, where only field desorption (FD) mightprovide better results (Montaudo & Lattimer, 2002). Unfortu-nately, this ionization technique is not much widespread.

One of these articles described the analysis of fully saturatedpolyethylenes (PE) (Keki et al., 2008a). ESI andMALDI usuallyfail to ionize PE because of the lack of effective sites for adductformation, protonation, or deprotonation. The only successfulanalysiswithMALDI or LDI involved the use of cobalt asmatrix,silver as cationizing agent (which lead to fragmentation), andderivatization (which is time-consuming, and can lead to biased

results because of incomplete derivatization). With negative-ionAPPI with CCl4 as a solvent and toluene as a dopant, PEwith twohydrogen atoms, or one hydrogen and one hydroxyl, as end-groups could be detected as MCl� with a satisfying S/N ratio.Figure 9a shows the APPI mass spectrum obtained from adihydrogen-terminated PE—a totally saturated polymer with noheteroatom. In the positive-ion mode, extensive fragmentationwas observed.

In the other article (Keki et al., 2008b), the analysis ofpolyisobutene derivatives (PIB) was described. As for PE, thelack of effective ionization sites makes difficult, if notimpossible, the analysis with ESI and MALDI. MALDI spectracould be obtained only if the polymer chain contains an aromaticor a polar moieties. ESI could be used only with low molecularweight (soluble in ESI-compatible solvent) and after derivatiza-tion to have a carboxylic acid end-group (able to bear a negativecharge). Two of the polymers studied in this work were derivedfrom aromatic moieties with dihydroxy or diolefinic end-groups.The third contained no aromatic moieties and had a mono-hydroxy end-group (and consequently was never ionized byMALDI or ESI). Positive-ion APPI detected the polymers asMHþ ions. However, as for PE, important fragmentations led tounderestimated average molecular mass and polydispersityindex. In contrast, APPI in the negative-ion mode, withchlorinated solvents and toluene as a dopant, led to excellentquality spectra (Fig. 9b). In this work, the influence of the tolueneconcentration on the intensity has been studied, and wasexplained with a mechanism that included the photoionizationof toluene, the formation of chloride ions from the chlorinatedsolvent by dissociative electron capture, the formation ofchlorinated adduct ions, and charge-recombination reactionsbetween the toluene radical cation, chloride ions, and chlorinatedadduct ions. In those two examples, the polymer could be ionizedby attachment of a Cl� on a hydrogen atom of a repeat unit,whatever the nature of the end-groups. The possible ionization ofnon-polar compounds is a huge advantage over ESI andMALDI.Moreover, direct coupling with LC is possible (unlike withMALDI), and the method is compatiblewith solvents that cannotbe used with ESI.

V. CONCLUSION

APCI and APPI are powerful ionization techniques for MSanalysis of synthetic polymers. A major advantage of APCI andAPPI is their suitability to couple chromatographic methods.Direct coupling can be easier than with ESI (not to mentionMALDI) because of a good tolerance to high flow rates. Thecompatibility with a much larger range of solvents than ESIallows the coupling with the main chromatographic modes:RPLC, NPLC, and SEC. The LC/MS coupling enables theidentification of the compounds in chromatographic peaksunambiguously, prevents the signal-suppression effects and theoverlaps between isobaric species frequently encountered withdirect-MS methods. The strength of this coupling has been well-documented for APCI-MS but not yet for APPI-MS. Among themany other advantages of APCI-MS and APPI-MS, one can notethe possible analysis of species that might not be detected withthe usual ionization techniques (MALDI-MS or ESI-MS).Indeed, unlike ESI, APPI, and APCI allow the use of low-polarity solvents needed to dissolve the most-apolar polymers.The gas-phase ionization process can make possible the

& TERRIER ET AL.


ionization of these apolar species for which ESI and MALDImight fail. However, the range of studied polymers is still narrow,and must be extended. APCI and APPI sources provide stable,strong signals (in positive- or negative-ion modes) and widelinear response ranges (which could be useful for quantitativeapplications). The mass spectra are easy to interpret: only singlycharged ions are formed; thus, there is no overlap amongmultiplecharge states as in ESI. APCI and APPI are ideal for the analysisof low-mass polymers, where MALDI-TOF cannot be used dueto interferences with matrix peaks. On the other hand, ionizationmechanisms in APCI or APPI are not yet fully understood, andsome fragmentations (thermal decomposition or up-front CID)not always well-identified and controlled. Nonetheless, theirrespective roles are decisive for the most reliable estimation ofthe average molecular mass and polydispersity indexes. Furtherfundamental studies should be carried out with small modelcompounds of polymeric chains. In addition, there is clearly alack of thermochemical data for polymers.

Lastly, it is noteworthy that commercial dual ion sourcesnow allow an automatic switch between two ionization methods(ESI/APCI; APCI/APPI or ESI/APPI) and between the twopolarity modes, all over the elution time. Those new sourcesshould create opportunities and stimulate research and applica-tions for polymer analysis.

VI. ABBREVIATIONS

AAEO alkylamine ethoxylateAEO alcohol ethoxylateAPCI atmospheric pressure chemical ionization

APEO alkylphenol ethoxylateAPO alcohol propoxylateAPPI atmospheric pressure photoionizationCID collision-induced dissociationDp degree of polymerizationESI electrospray ionizationFAB fast atom bombardmentFAEO fatty alcohol ethoxylateFAPO fatty alcohol propoxylateFD field desorptionGC gas chromatographyGC/MS gas chromatography coupled to mass spectrometryIp index of polydispersityLA lactic acidLAS linear alkylbenzene sulfonateLC liquid chromatographyLC/MS liquid chromatography coupled to mass spectrometryLS light-scatteringMALDI matrix-assisted laser desorption/ionizationMn average molecular weightMS mass spectrometryMS/MS tandem mass spectrometryNMR nuclear magnetic resonanceNPLC normal-phase liquid chromatographyPCL poly(caprolactone)PBT poly(butylene terephthalate)PDMS poly(dimethylsiloxane)PE polyethylenePEG poly(ethylene glycol)PEO poly(ethylene oxide)

FIGURE 9. APPI-MS (�) spectra of a dihydrogen terminated polyethylene (a) (reprinted with permission

from Keki et al. � 2008 American Chemical Society) and a diolefin telechelic polyisobutylene (b)(reprinted with permission from Keki et al.� 2008 Elsevier). Spectra were recorded using a MicroTOF-Q

type Qq-TOFMS instrument (Bruker), which was equipped with an APPI source (PhotoMate, Kr discharge

lamp, VUV photons of 10.0 and 10.6 eV in an intensity ratio of 4:1, Syagen Technology, Inc., Tustin, CA).

PE was dissolved at a concentration of 0.2mg/mL in hot toluene dopant. PIBs were dissolved at a

concentration of 0.5mM in mixtures of toluene (dopant) and CCl4 (solvent). The analyte solutions were

introduced directly into the APPI source with a syringe pump at a flow rate of 20 mL/min (PE) or 25 mL/min

(PIB). The carrier flow rate of CCl4 solvent was 200 mL/min through a T-piece. The APPI source heater was

kept at 3508C (PE) or 4008C (PIB). The total volumetric gas flow (N2) was estimated to be about 50 cm3/sec.



PET poly(ethylene terephthalate)PIB poly(isobutylene)PMS poly(methylsiloxane)PPG poly(propylene glycol)PPO poly(propylene oxide)PTHF poly(tetrahydrofuran)RI refractive indexRIC reconstructed ion chromatogramRPLC reverse-phase liquid chromatographySEC size exclusion chromatographySIM selected ions monitoringSPE solid-phase extractionTIC total ion currentUV ultraviolet

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