Buffer gas modifiers effect resolution in ion mobility spectrometry through selective ion-molecule...

Research Article

Received: 15 November 2011 Revised: 24 June 2012 Accepted: 26 June 2012 Published online in Wiley Online Library

Rapid Commun. Mass Spectrom. 2012, 26, 2211–2223

Buffer gas modifiers effect resolution in ion mobilityspectrometry through selective ion-molecule clustering reactions

Roberto Fernández-Maestre1, Ching Wu2 and Herbert H. Hill Jr.3*1Universidad de Cartagena, Programa de Química, Cartagena, Colombia2Excellims Corporation, 20 Main Street, Acton, MA, USA3Department of Chemistry, Washington State University, Pullman, WA 99163, USA

RATIONALE:When polar molecules (modifiers) are introduced into the buffer gas of an ion mobility spectrometer, mostion mobilities decrease due to the formation of ion-modifier clusters.METHODS: We used ethyl lactate, nitrobenzene, 2-butanol, and tetrahydrofuran-2-carbonitrile as buffer gas modifiersand electrospray ionization ion mobility spectrometry (IMS) coupled to quadrupole mass spectrometry. Ethyl lactate,nitrobenzene, and tetrahydrofuran-2-carbonitrile had not been tested as buffer gas modifiers and 2-butanol had not beenused with basic amino acids.RESULTS: The ion mobilities of several diamines (arginine, histidine, lysine, and atenolol) were not affected or only slightlyreduced when these modifiers were introduced into the buffer gas (3.4% average reduction in an analyte’s mobility for thethreemodifiers). Intramolecular bridges caused limited change in the ionmobilities of diamineswhenmodifiers were addedto the buffer gas; these bridges hindered the attachment of modifier molecules to the positive charge of ions and delocalizedthe charge, which deterred clustering. There was also a tendency towards large changes in ionmobilitywhen themass of theanalyte decreased; ethanolamine, the smallest compound tested, had the largest reduction in ionmobility with the introduc-tion of modifiers into the buffer gas (61%). These differences in mobilities, together with the lack of shift in bridge-formingions, were used to separate ions that overlapped in IMS, such as isoleucine and lysine, and arginine and phenylalanine, andmade possible the prediction of separation or not of overlapping ions.CONCLUSIONS: The introduction of modifiers into the buffer gas in IMS can selectively alter the mobilities ofanalytes to aid in compound identification and/or enable the separation of overlapping analyte peaks. Copyright© 2012 John Wiley & Sons, Ltd.

(wileyonlinelibrary.com) DOI: 10.1002/rcm.6335

Drift tube ion mobility spectrometry (IMS) is a time-of-flightanalytical technique that uses the distinctive mobilities of ionsin a gas phase for the separation and identification of analytes.Ion mobility spectrometry has been applied to the separationand detection of a wide variety of chemicals such as heroinand cocaine,[1] explosives,[2] halogenated compounds,[3] explo-sives in hair,[4] veterinary drugs in meat,[5] methamphetaminesin human serum,[6] pharmaceuticals for equipment cleaningverification,[7] carbohydrate isomers,[8] complex peptide mix-tures,[9] large non-covalent protein-ligand and protein-proteincomplexes,[10] metabolites,[11] and human plasma proteins.[12]

Several comprehensive reviews of IMS applications are avail-able[13,14] that demonstrate the breadth of applications of thisrapidly developing analytical separation technique. As withall separation methods, however, some compounds (ions inthe case of ion mobility spectrometry) elute at a similar timeand are not resolved from one another. The objective of thiswork is to investigate methods of modifying the buffer gas toeffect the resolution of difficult-to-resolve ions.

* Correspondence to: H. H. Hill Jr., Department of Chemistry,Washington State University, Pullman, WA 99163, USA.E-mail: [email protected]

Rapid Commun. Mass Spectrom. 2012, 26, 2211–2223

221

In IMS, separation is based on the different velocities thations acquire under the influence of an electric field. Becausethe velocities of ions are an inverse function of their size-to-charge ratios, ions of similar size have similar velocitiesand are difficult to separate by IMS. In electrospray ioniza-tion (ESI) IMS, singly charged, stable gas-phase ions arecreated in an ESI source. To generate these ions, ion mobilityspectrometers used with ESI have a desolvation regionwhere the charged droplets that are generated from the ESIprocess are stripped of solvent molecules by a countercur-rent of preheated buffer gas. Ions are pulsed into the driftregion, where they are accelerated by an electric field, butare continuously decelerated by collisions with the buffergas. This combination of collisions and accelerations therma-lizes the ions and averages their velocities to distinct valuesthat can be used to calculate a characteristic parametercalled the mobility constant, K:[15]

K ¼ nE¼ L2

V:td(1)

where v is the velocity of the ion in cm s–1, E the electric fieldin the drift region in V cm–1, L the length of the drift regionin cm, V the total voltage drop in volts across the drift region,and td the time that the ion spends traveling the distance L

Copyright © 2012 John Wiley & Sons, Ltd.

1

R. Fernández-Maestre, C. Wu and H. H. Hill Jr.

2212

in s. The velocity, n, is proportional to E for electric fields ofless than approximately 500 V cm–1 (at ambient pressure).[16]

In IMS, ion mobilities are normalized to standard pressureand temperature as reduced mobilities (K0, cm2 V–1 s–1),which are constants useful for identification purposes. Thisstandardization allows comparison of results in differentlaboratories by correcting for variations in environmentaland instrumental conditions:

K0 ¼ KP760

273T

(2)

where P is the pressure in the drift tube in Torr and T thebuffer gas temperature in Kelvin.[16] However, as noted asearly as the beginning of the twentieth century, these mobili-ties can be affected by the presence of neutral contaminantssuch as moisture in the buffer gas of an ion mobility drifttube.[17,18] Recently, modification of the buffer gas by theintroduction of small quantities of organic vapors has beenused to vary the arrival times of analyte ions. The addition ofketones to the buffer gas allowed the separation of ammoniafrom hydrazines[19,20] and the addition of 2-butanol enabledthe separation of enantiomers.[21]

In this paper the term ’modifier’ refers to traces of vaporsadded to the buffer gas to modify the ion separation charac-teristics while the term ’dopant’ refers to traces of vaporsadded to the ionization region of the IMS system to produceselectivity. Dopants mainly have been introduced to preferen-tially ionize compounds with higher proton affinities (asin the case of drugs) or higher electronegativities (as in thecase of explosives).[20] Dopants that have been added to ionmobility spectrometers include ammonia,[22] chloride ions,[23]

dichloromethane, methyl iodide, acetic acid, dimethyl sulfide,acetonitrile,[24] acetone,[25–27] dimethyl sulfoxide,[26–28]

water,[28] 5-nonanone,[27] 4-heptanone,[19] and ketones.[20]

A comprehensive review on the introduction of dopants inIMS was published by Puton et al. in 2008.[29]

In this work, we evaluated three new modifiers, ethyllactate, nitrobenzene, and tetrahydrofuran-2-carbonitrile,and compared their effects on ion mobilities with that of

Figure 1. Sketch of the electrospraymobility mass spectrometer.

wileyonlinelibrary.com/journal/rcm Copyright © 2012 John Wile

2-butanol, whichwas used previously. In addition, themechan-ism of mobility changes as a function of buffer gas modifica-tion was investigated.

EXPERIMENTAL

Instrument

An ESI atmospheric-pressure ion mobility spectrometercoupled to a quadrupole mass spectrometer through a40-mm pinhole was used in this investigation (Fig. 1). Themass spectrometer was an ABB Extrel (Pittsburgh, PA, USA)150-QC quadrupole (m/z 0–400), and was equipped with amodel 427 amplifier (Keithley Instruments, Cleveland, OH,USA) that amplified data from the electron multiplier detec-tor and sent it to the acquisition systems. Merlin software(version 3.0, ABB Extrel) controlled the mass spectrometerand collected the mass spectral data.

The ion mobility spectrometer was built at WashingtonState University (PullmanWA, USA), and has been describedin detail elsewhere.[30] Briefly, the drift tube consisted ofa desolvation and a drift region separated by a Bradbury-Nielsen ion gate. Both regions comprised 2.2" o.d., 2.0" i.d.stainless steel rings, insulated from each other by aluminarings of the same size (99.6% Al2O3, Advalue Tech., Tucson,AZ, USA). A counterbore into each metallic ring supplied asupport to hold the neighboring ceramic insulator. Theinsulating spacers and steel rings were horizontally stackedin an interlocking design. All rings were kept together in a2.5" o.d., 2.3" i.d. alumina tube placed in an aluminumheating case. Steel rings were connected in series by high-temperature resistors. The resistors were 1-MΩ (driftregion) or 0.5 MΩ (desolvation region) (Caddock Electro-nics Inc., Riverside, CA, USA, �1%). When an electricalpotential was applied to the first ring, an electric fieldof 432 V cm–1 developed in the drift tube.[31] A targetscreen was placed at the first ring of the desolvation region.This screen helped to electrospray the samples, andwas made out of 2-mm stainless-steel mesh with a 0.5-cmround hole in the center. A countercurrent of preheated

ionization atmospheric-pressure ion

y & Sons, Ltd. Rapid Commun. Mass Spectrom. 2012, 26, 2211–2223

Buffer gas modifiers effect resolution in IMS by clustering

N2 buffer gas was introduced at the low-voltage end of thedrift tube through a stainless-steel tube. The buffer gas washeated by passing it through a 2-m long stainless-steel tubecoiled inside an aluminum heating block (Fig. 1).The gate had approximately 80 parallel 75-mm Alloy 46

wires (California Fine Wire Co., Grove Beach, CA, USA)separated 0.6 mm from each other. Ions were preventedfrom passing to the drift region by applying a closurepotential that was 40 V higher for a set of wires and 40 Vlower for the other set than the voltage of the gate whenit was open. For these experiments the gate voltages were10840 V and 10760 V. The open-gate voltage was that of asteel ring in the position of the gate in the tube, 10800 V.This closure voltage was disconnected for 0.1 ms so that anarrow pulse of ions entered the drift region. The mobilityspectrometer was run at ambient pressure (685–710 Torr inPullman, WA, USA). LabView software (National Instru-ments, Austin, TX, USA), modified in lab, collected theIMS data and controlled the ion gate. Igor Pro 5.0.3 (Wave-Metrics, Portland, OR, USA) was used to process spectraldata text files. The electronics for IMS data acquisition werebuilt at Washington State University.[32]

Typical operating parameters used with this instrumentwere: ESI flow rate, 3 mL min–1; reaction region length, 7.5 cm;drift tube length, 25.0 cm; ESI voltage, 15.6 kV; voltage at firstring, 12.12 kV; voltage at the gate, 10.80� 0.01 kV; gate closurepotential, �40 V; gate pulse width, 0.1 ms; scan time, 35 ms;pressure, 680–710 Torr; buffer gas, nitrogen; buffer gas tem-perature, 150� 2 �C; buffer gas flow rate, 1 Lmin–1; modifierflow rates, 1 to 50 mL h–1 (Table 1).

Modes of operation

Ion mobility spectra were obtained in two modes. In IMSmode, the DC voltages to the mass spectrometer wereremoved and the quadrupole was operated in the radio-frequency (RF)-only condition, allowing all the ions to passthrough the mass spectrometer to the ion detector. Total ionmobility spectra were obtained in this mode. In SIMIMSmode (single ion monitoring), the DC and RF voltagesin the mass spectrometer were set to allow only ions of a

Table 1. Summary of the operating conditions for the ionmobility spectrometer

Parameter Setting

Reaction region length 7.5 cmDrift region length 25.0 cmESI voltage 15.6 kVVoltage at first ring 12.12 kVESI flow 3 mL min–1

Voltage at the gate 10.80� 0.01 kVGate closure potential �40 VGate pulse width 0.1 msScan time 35 msBuffer gas NitrogenBuffer gas temperature 150� 2 �CBuffer gas flow 930 mL min–1

Modifier flow rate 1–50 mL h–1

Copyright © 2012Rapid Commun. Mass Spectrom. 2012, 26, 2211–2223

specific mass or a selection of specific masses to reach thedetector. Mass-selected ion mobility spectra were obtainedin this mode. To obtain a complete mass spectrum of asample, the gate of the ion mobility spectrometer was heldopen and all the ions migrated through the IMS region tothe mass spectrometer without pulsing.

Materials and reagents

2,4-Dimethylpyridine (2,4-lutidine), 2,6-di-tert-butyl pyridine(DTBP), 2-butanol, arginine, atenolol, desipramine, ethanol-amine, ethyl lactate, histidine, lysine, nitrobenzene, serine,tetrahydrofuran-2-carbonitrile, the drug valinol, and tetra-butylammonium (TBA), tetraethylammonium (TEA), tetra-methylammonium (TMA), and tetrapropylammonium (TPA)chlorides (ACS reagent grade, ≥98% purity) were purchasedfrom Sigma Aldrich Chemical Co. (Milwaukee, WI, USA).Ethyl lactate, tetrahydrofuran-2-carbonitrile, 2-butanol, andnitrobenzene were selected as modifiers because they havedifferent functionalities and produce different steric effects.Nitrobenzene has a low proton affinity and does not chargethrough proton transfer reactions with analytes. Therefore,nitrobenzene does not compete for charge and can serve asa comparison with other modifiers that might neutralizethe analytes as they drift through the buffer gas. The analyteswere chosen to have a range of sizes, functionalities, andsteric effects.

Sample preparation and introduction

Standard solutions (100 mM) of the analytes were preparedin ESI solution (47.5% methanol/47.5% water/5% aceticacid). Liquid samples or blank solution (ESI solution)were continuously infused by ESI using 250-mL syringes(Hamilton, Reno, NV, USA) at a flow rate of 3 mL min–1 intoa 30-cm-long, 100-mM i.d. capillary (Polymicro Technologies,Phoenix, AZ, USA). This capillary was connected, through astainless-steel union (Valco, Houston, TX, USA), to a 50-mmi.d. silica capillary. The end of this capillary was centered atthe target screen placed at the entrance of the mobilityspectrometer. A voltage of 15.6 kV (or 3.5 kV bias withrespect to the target screen) was applied to the stainlesssteel union to produce positive electrosprayed ions. Toprevent cross contamination between analytes, differentsyringes and capillaries were used for every compoundwhenever possible.

221

Modifier introduction

The liquid modifiers were injected into the buffer gas line(pumped by a model 210 pump; KD Scientific, Holliston,MA, USA) before the buffer gas heater using gas-tightsyringes to avoid leaking. Modifiers were introduced througha 10-cm-long, 50-mm i.d. silica capillary into the buffer gas lineusing a cross-junction (Fig. 1). The purpose of introducing themodifier before the buffer gas heater was to provide a longerpath in order to obtain a homogeneous mixture of the modi-fier with the buffer gas. Heating tape (OMEGA Engineering,Stamford, CT, USA) was wrapped around the buffer gas tubeand cross to help vaporize the modifier.

wileyonlinelibrary.com/journal/rcmJohn Wiley & Sons, Ltd.

3


2214

Calibration

To account for errors produced by inaccurate measurement ofdrift tube length, temperature, voltages, and pressure, thereduced mobilities used in this study were determined fromthe known reduced mobility values of standards[33] usingthe relationship:

K0 unknownð ÞK0 standardð Þ

¼ td standardð Þtd unknownð Þ

(3)

where K0 is the reduced mobility in cm2V�1s�1 and td the drifttime in ms. 2,4-Lutidine and DTBP were used as chemicalstandards to calibrate the reduced mobilities of the analytesused in this study.

Purity of the buffer gas

Because these experiments investigated the modification of thebuffer gas it was essential to ensure that the buffer gaswas pureprior to modification. The purity of the buffer gas was evalu-ated using two IMS standards, DTBP and 2,4-lutidine (24L).DTBP is insensitive to buffer gas contamination while 24L isknown to be sensitive to buffer gas contamination. The reducedmobility value was calculated for 24L using DTBP as theknown standard in Eqn. (3) above. If the reduced mobilitycalculated for 24L matched its literature value, the instrumentwas considered to be free of contamination. If the reducedmobility calculated for 24L did not match its literature value,the instrument was cleaned and the test for buffer gas puritywas repeated until the buffer gas was free of contamination.[34]

Identification of compounds

All analytes were detected in the mass spectrometer as MH+

or cluster ions. Analytes were identified in the mass spectra bytheir molecular weights determined from these protonatedmolecules or clusters. Analyte peaks in the mobility spectrumwere identified using SIMIMS and by comparing their reducedmobilities with literature values.

Figure 2. Reduction in analyte’s mobility with the intro-duction of ethyl lactate modifier in the buffer gas. Mobility(a) and mass (b) spectra when no modifier was added to thenitrogen buffer gas. Mobility (c–j) and mass (d–j) spectra whenthe concentration of ethyl lactate increased in the buffer gas.

RESULTS AND DISCUSSION

Ethyl lactate as a buffer gas modifier

Effect of ethyl lactate modifier on the ion mobility of ethanolamine

Figure 2 illustrates the reduction in the ion mobility of ethano-lamine when ethyl lactate was introduced as the modifier intothe buffer gas of the ion mobility spectrometer. The drift timeof ethanolamine ions increased more than 10 ms as the ethyllactate concentration increased from 0.0 to 2.8 mmol m–3

(104 ppmv), which corresponded to a 41% reduction in mobi-lity. Figure 2 shows clusters of ethanolamine (E) ions withethyl lactate (L), sodium ions, and reactant ions in the buffergas in the mobility andmass spectra; sodium ions are ubiqui-tous, arising as trace contaminants from the electrospraysolvent. LNa+ ions were formed because ethyl lactate wasmuch more concentrated in the buffer gas than analytes orreactant ions (more than 100 times); analyte-Na+ adductswere not visible.Figures 2(a) and 2(b) are the mobility and mass spectra,

respectively, when no modifier was added to the nitrogenbuffer gas. Three mobility peaks are seen in Fig. 2(a); the first


and last peaks in the mobility spectrum (Fig. 2(a)) were thoseof the solvent background ionwhile themiddle peakwas proto-nated ethanolamine (m/z 62). As expected, (1) the intensity ofEL2H

+ increased with respect to ELH+ as the concentration ofethyl lactate in the buffer gas increased, and (2) the EL3H

+ andL3Na+ ions only appeared at high concentrations.

All the reactant ions disappeared from the spectra when theethyl lactate modifier was added to the buffer gas; ethyllactate was protonated and also clustered to ethanolamineand sodium to form the species LnH

+, ELnH+, LnH3O

+,ELnH3O

+, and LnNa+. The LnNa+ species was seen in all thespectra where modifier was added to the buffer gas.

When ethyl lactate was added as the modifier, clusters ofthe ethanolamine were seen in the mass spectrum and theanalyte peak shifted to longer drift times. Clusters withethanolamine occurred at 24.5 ms, ELnH

+, and 26.2 ms



ELnH3O+ in the mobility spectrum (Fig. 2(c)). These clusters

also appear in Figs. 2(e), 2(g), and 2(i) at longer drift timeswhen the concentration of ethyl lactate increased in the buffergas. Clusters of ethanolamine ions with one to three ethyllactate molecules occurred at m/z 180 and 298 (Figs. 2(d),2(f), 2(h), and 2(j)) and m/z 416 (Figs. 2(h) and 2(j)) in the massspectra. The mass spectra also show that the ratio EL2H

+ toELH+ increased with the concentration of ethyl lactate inthe buffer gas and that EL3H

+ only appeared at high concen-trations of modifier, indicating that there was increasing clus-tering as a function of increased ethyl lactate concentration.A maximum of three molecules of ethyl lactate can cluster

to ethanolamine ions; this number corresponds to the numberof hydrogen atoms attached to the positively chargednitrogen of protonated ethanolamine, C2H4ONH3

+, availablefor binding modifier molecules. These results agree withthe findings of Bollan et al.[20] who reported that the numberof ketone molecules binding to hydrazines and ammoniaanalytes when the buffer gas was modified depended on thenumber of hydrogen atoms on the protonated nitrogen of theanalytes (four for ammonia, three for hydrazine, two formonomethyl hydrazine, and one for 1,1-dimethylhydrazine).

Figure 3. Ethyl lactate clustering with ESI solvent and serineions. (a, c) IMS and (b, d) mass spectra of ESI solvent andserine (S) when ethyl lactate (L) modifier was introduced intothe buffer gas at a concentration of 1.7 mmol m–3 in (a) and (b)or 0.33 mmol m–3 in (c) and (d). (a, b) ESI solvent producedextensive clustering due to the relatively small size and lowproton affinity of reactant ions. (c, d) Serine formed abundantclusters as a consequence of its lack of steric hindrance andsmall size. SH+ and SLnH

+ had the same drift times andappeared as a single peak in the mobility spectrum. Reactantions were completely stripped of their charge by the modi-fiers and disappeared from the spectra.


221

Effect of ethyl lactate modifier on the ion mobility of serine

Figures 3(a) and 3(b) show the background ions when onlyethyl lactate was added to the buffer gas. Under these condi-tions the background ions were independent of the electro-spray solvent and were controlled by the excess of modifieradded to the buffer gas. The presence of ethyl lactate depletedall reactant ions by clustering with H+ and H3O

+. In addition,the sodium ion cluster of ethyl lactate was observed. Threebackground ion species were identified: LnH

+, LnH3O+, and

LnNa+ with drift times of 25.0, 25.5, and 29.1 ms, respectively.Figures 2(c), 2(e), 2(g), and 2(i) show a tail between the

two peaks at ~25 ms, which means that the ion at26.2 ms, ELnH3O

+, was converting into that at 24.5 ms,ELnH

+, during the drift time. The tail can be used to calcu-late rate constants of ion-molecule or decomposition reac-tions.[35] However, ELn.H

+ and ELn.H3O+ were expected to

overlap. In IMS, there should be a fast forward and back-ward reaction between water molecules and cluster ions inthe drift region:

ELHþ þH2O↔ELH3Oþ

Nevertheless, the reactant ions, all protonated analytes,and Na+ ions were ’sequestered’ by ethyl lactate due to itshigh concentration and their clusters were available mostlyfor equilibria with the free modifier, which separated ELnH

+

and ELnH3O+ clusters. Figures 2 and 5 show how ethyl

lactate depleted all the reactant ions by clustering with H+

and H3O+ and probably with water, sequestering it, making

water unavailable for the equilibrium depicted above. Ethyllactate also separated the pair of ions, L2H

+ and L2H3O+,

from the pair, L3H+ and L3H3O

+ (Fig. 4), which were alsoexpected to overlap. The identity of these clusters in theIMS spectra was confirmed in SIMIMS mode. That thestrongest reactant ion peak clusters were not LH+, LH3O

+,or LNa+ but L2H

+, L2H3O+, or L2Na+ confirmed this seques-

tration. No clusters with two or more water molecules wereobserved in the mass spectra here or in earlier work whenmodifiers were introduced into the buffer gas,[34,36] whichalso confirmed the sequestration of water. On the contrary,clusters of analyte with up to eleven molecules of water wereseen when water was introduced as a modifier.[34]

Clustering with ethyl lactate was evident also in the mobi-lity and mass spectra of the amino acid serine (Figs. 3(c) and3(d)). Clusters of ethyl lactate with the reactant ionsoccurred at 25.0 ms, LnH

+, 25.5 ms, LnH3O+, and 29.1 ms,

LnNa+, in the mobility spectrum (Fig. 3(a)); in the massspectrum (Fig. 3(b)), the clusters occurred at m/z 119 LH+,136 LH3O

+, 237 L2H+, 255 L2H3O

+, 259 L2Na+, 355 L3H+,

373 L3H3O+, and 377 L3Na+. Most of these ions in the IMS

and MS spectra also appear in Fig. 2 but clustered to ethano-lamine. Ethyl lactate was present mainly as LH+ and LH3O

+

based on the peak intensities shown in Fig. 3(a). Themechanism of formation of these ions was clustering withthe reactant ions followed by stripping of the charge. Reac-tant ions were completely stripped of their charge by themodifiers and disappeared from the spectra. LNa+ wasformed but not analyte-Na+ clusters, because ethyl lactatewas present at a much higher concentration in the buffergas than the analytes. Serine-ethyl lactate clusters, SLnH

+,occurred at 28.1 ms in the mobility spectrum (Fig. 3(c)) and


5

Figure 4. Changes in mobilities of selected ions with modi-fiers in the buffer gas. (a, c) Themobilities of tetraalkylammo-nium and arginine ions did not change, and for DTBP andatenolol ions changed minimally with modifiers in the buffergas due to steric hindrance, which impeded the attachmentof modifier molecules to the positive charge of these ions.Analyte ions with lower steric hindrance such as 2,4-lutidine,desipramine, ethanolamine, serine, and valinol showedlarger changes in mobility. (b) Changes in mobilities of ethyllactate cluster ions with increasing concentrations of ethyllactate. The mobilities of both cluster ions coincided withinfamilies: protonated, hydrated, and sodiated clusters hadthe same mobility.



2216

at m/z 224 SLH+ and 342 SL2H+ in the mass spectrum (Fig. 3

(d)). SLnH+ ions were formed in the reaction region and not

at the atmospheric/vacuum interface of the IMS systemwith the mass spectrometer because the drift times of serineions increased with the concentration of ethyl lactate inthe buffer gas, indicating the formation of larger serine ion-ethyl lactate clusters, SLnH

+, as a function of increasingmodifier concentration.

SH+ and SLnH+ had the same drift times (Fig. 3(c)), appear-

ing as a single peak in the mobility spectrum (Fig. 3(c)), andindicating that these ion species were in equilibrium and thecharged speciesmigrated through the drift tube. Based on theseresults, the equilibria shown in Scheme 1 are proposed to occurin the drift tube. These reactions must be rapid during thepassage of ions through the drift tube. Thus, the drift time ofserine ions was a weighted average of the drift times of itsfast protonated molecule and the slow cluster ions. Similararguments can be used to demonstrate that peaks in the massspectra of other analytes corresponded to cluster peaks.

In summary, when ethyl lactate was used as a modifier fornitrogen buffer gas, the ion mobility of serine decreaseddue to the formation of serine ion-ethyl lactate clusters. Themaximum cluster size was limited by the number of hydro-gen atoms attached to the amine nitrogen. The ion-ethyllactate exchange rate was sufficiently rapid that the ionmigrated as an average ion cluster through the buffer gas.

Effect of ethyl lactate on the mobility of other ions

Changes in mobilities with the introduction of ethyl lactate inthe buffer gas are shown in Figs. 4(a) and 4(b). These changesare summarized as %ΔK0 values, where %ΔK0 was definedas the percentage difference between K0 in N2-only buffergas and K0 when a modifier was introduced into the buffergas at a given concentration. The test ions showed the follow-ing %ΔK0 values: 2,4-lutidine (24%), atenolol (7.0%), desipra-mine (12%), DTBP (1.5%), ethanolamine (41%), serine (30%),TBA (0.3%), TEA (0.5%), TMA (1.0%), TPA (0.1%), and valinol(28%) when the ethyl lactate concentration increased in

Scheme 1. Clustering equilibria.


Table 2. Percentage decrease in K0 values, %ΔK0, for selected ions when modifiers were introduced into the buffer gas. Theconcentrations of modifier increased in the buffer gas from 0 to 1.7, 0.95, and 6.8 mmol m–3 for ethyl lactate, nitrobenzene, and2-butanol, respectively; for ethyl lactate clusters, ethyl lactate increased in the buffer gas from 0.33 (12 ppmv) to 1.7 mmol m–3.Differences of less than 0.32 units in %ΔK0 may arise from the maximum accepted standard deviation of the drift timemeasurements (0.05 ms)

Modifiers

Ions Ethyl lactate Nitrobenzene 2-Butanol

2,4-Lutidine.H+ 24 13 5.6b

LnH+ 6.4

LnH3O+ 10

LnNa+ 4.3Arginine.H+ 9.8 2.7 0.3Atenolol.H+ 7.0 2.0 0.7a

Desipramine.H+ 12 3.0 1.1DTBP.H+ 1.5 0.1 2.2b

Ethanolamine.H+ 41 37 19Histidine.H+ 4.1 2.3 1.1Lysine.H+ 4.3 2.1 1.1Serine.H+ 30 25 14b

TBA 0.3 0.1 0.3b

TEA 0.5 0.3 1.0b

TMA 1.0 1.0 1.0b

TPA 0.1 0.5 0.0b

Valinol.H+ 28 21 9.8b

aAverage %ΔK0 at 100, 150, 200, and 250�C.bFernandez-Maestre et al.[36] Differences of less than 0.32 units in %ΔK0 may arise from the standard deviation of the drift timemeasurements (0.05 ms).


221

the buffer gas from 0.0 to 1.7 mmol m–3, and LnH+ (6.4%),

LnH3O+ (10%), and LnNa+ (4.3%) as ethyl lactate increased

in the buffer gas from 0.33 (12 ppmv) to 2.8 mmol m–3

(1.0� 102 ppmv). All ion mobilities decreased (average%ΔK0 value of 13%, excluding the tetraalkylammonium andDTBP ions) when ethyl lactate was introduced into the buffergas at 1.7 mmol m–3; tetraalkylammonium ions and DTBPshowed only reduced %ΔK0 values (≤1.5%) at this ethyllactate concentration.

Effect of other modifiers on ion mobility

In general, the formation of ion clusters decreased ion mobili-ties by increasing the collision cross-sections of the ions. Table 2summarizes the changes in mobilities of ions of 2,4-lutidine,arginine, DTBP, ethanolamine, serine, valinol, the drugs ateno-lol and desipramine, and the TBA, TEA, TMA, and TPAions when modifiers were introduced into the buffer gas. Inthese experiments, 2-butanol, ethyl lactate, nitrobenzene,and tetrahydrofuran-2-carbonitrile were used as modifiers.Ethyl lactate, nitrobenzene, and tetrahydrofuran-2-carbonitrilehad not previously been tested as buffer gas modifiers, and 2-butanol had not been used as amodifierwith basic amino acids.

2-Butanol as a buffer gas modifier

When the 2-butanol concentration increased in the buffer gasfrom 0.0 to 6.8 mmol m–3 (2.5� 102 ppmv), the %ΔK0 valuesfor diamine ions were: atenolol (0.7%), arginine (0.3%), andhistidine and lysine (1.1%) (Table 2). In a previous work,[36]

the mobilities of a series of analytes decreased (average %ΔK0

value of 10%) when 2-butanol was introduced into the buffer


gas under the same experimental conditions as used here. Inthis work, only diamines were tested with 2-butanol, and theyshowed a low responsiveness to the introduction of thismodifier into the buffer gas (average %ΔK0 value of 0.8%).

Nitrobenzene as a buffer gas modifier

The changes in mobilities with the introduction of nitroben-zene in the buffer gas are shown in Fig. 4(c). Ions of the testcompounds produced the following %ΔK0 values whenthe nitrobenzene concentration increased in the buffer gasfrom 0.0 to 1.0 mmol m–3 (36 ppmv): 2,4-lutidine (13%),arginine (2.7%), atenolol (2.0%), DTBP (0.1%), ethanolamine(37%), TBA (0.1%), TEA (0.3%), TMA (1.0%), TPA (0.5%), andvalinol (21%) (Table 2). In general, decreases in ion mobilitywere observed when 1.0 mmol m–3 nitrobenzene was intro-duced into the buffer gas (average %ΔK0 value of 7.8%). Onlysmall reductions in ion mobility were observed for diamines,DTBP, and tetraalkylammonium ions (%ΔK0 values ≤2.7%).

Tetrahydrofuran-2-carbonitrile as a buffer gas modifier

When tetrahydrofuran-2-carbonitrile (tHFCN) was used as amodifier, ions were not observed in the mass spectra fora-amino acids and valinol at concentrations lower than3.3 mmol m–3 (125 ppmv) of this modifier in the buffer gas.However, tetraalkylammonium and DTBP ions were observedat this concentration. The absence of some analyte peaks fromthe mass spectrum when tHFCN is used as a modifier can beattributed to charge stripping. As the protonated analytemolecules drift through the buffer gas, they behave as reactantions and protonate the neutral modifier. The proton affinityof tHFCN stripped off the charge of the analyte ions except


7


2218

for those from DTBP, where steric hindrance deterredthe approach of the modifier to the positive charge(as explained below), and those inherently ionic speciessuch as tetraalkylammonium ions (data not shown).

Effects of steric hindrance, modifier saturation, andanalyte size on changes in ion mobility due to clusteringwith modifiers

In Fig. 4, several common characteristics of changes in mobi-lity are observed when modifiers were introduced into thebuffer gas. The ion mobilities of the two pyridines changedto different extents when the modifiers were introduced intothe buffer gas. The mobilities of DTBP ions decreased lessthan those of 2,4-lutidine ions (average %ΔK0 values of0.8% and 19%, respectively) with ethyl lactate and nitroben-zene modifiers. Figures 5(a) and 5(b) show the mobility andmass spectra, respectively, of a DTBP/2,4-lutidine mixture

Figure 5. Clustering in DTBP, 2,4-lutidine, and(b, d) mass spectra of 2,4-lutidine, DTBP1.1 mmol m–3 (42 ppmv) of ethyl lactate (L)gas. (a, b) 2,4-lutidine produced a large MS clnated molecule; in contrast, DTBP ions did nomass spectrum; these features agree with the fmore affected by the modifier than that of DT2-butanol.[37] (c, d) Tetraalkylammonium ionTBA ions and LnNa+ overlapped in the mobil


when the buffer gas was spiked with 1.1 mmol m–3 of ethyllactate. No cluster peaks of DTBP ions were visible, but a1:1 2,4-lutidine ion-ethyl lactate cluster occurred at 22 ms inthe mobility spectrum and m/z 226 in the mass spectrum. Thislack of clustering of DTBP ions was due to the strong sterichindrance exerted on the charge by the large tert-butyl substi-tuents, in positions 2 and 6 on the ring. These substituentsshielded the protonated nitrogen atom of DTBP from modi-fier molecules. The two small methyl groups of 2,4-lutidine,located at positions 2 and 4 on the ring, shielded the nitrogenatom less effectively. This propensity of the DTBP ion to resistcluster formation explains its small mobility change withmodifiers in the buffer gas.

Figure 4 also shows that the mobilities of tetraalkylammo-nium ions decreased by ≤1% when the buffer gas was spikedwith ethyl lactate or nitrobenzene. When 1.1 mmol m–3 of ethyllactate was introduced into the buffer gas (Fig. 5(c)), tetraalky-lammonium ions showed single and sharp peaks (i.e. they did

tetraalkylammonium ions. (a, c) IMS and, and tetraalkylammonium ions whenmodifier were introduced into the bufferuster with the modifier and a small proto-t show clustering with ethyl lactate in theact that the ion mobility of 2,4-lutidine wasBP ions and that from previous work withs did not cluster due to steric hindrance;ity spectrum.



221

not produce clusters) occurring at 16.7 (TMA), 20.3 (TEA),24.8 (TPA), and 29.4 (TBA) ms in the mobility spectrum andat m/z 75.2 (TMA), 131.2 (TEA), 186.4 (TPA), and 243.5 (TBA)in the mass spectrum (Fig. 5(d)). This lack of clustering was aconsequence of the steric hindrance exerted by the four alkylsubstituents in tetraalkylammonium ions that deterredthe attachment of ethyl lactate molecules to the nitrogenpositive charge and delocalized this charge, thus weakeningthe ion-modifier interactions.[15,37] This lack of clustering oftetraalkylammonium ions explains their small mobilitychange with modifiers in the buffer gas.Figure 4 shows that the largest reductions in mobility were

obtained with the first introduction of modifier, and onlysmall reductions were achieved with further incrementsof modifier concentration, which caused a plateau in the K0

values at high concentrations of modifier. In Fig. 2(a), thelargest increase in the drift time of ethanolamine ions (60%)was obtained when the ethyl lactate concentration increasedfrom 0.0 to 0.33 mmol m–3 (12 ppmv), and only a small reduc-tion (8.4%) was obtained for a larger increment of concentra-tion (from 0.33 to 1.7 mmol m–3). Small reductions in mobilitywith the introduction of ethyl lactate into the buffer gas mayindicate modifier saturation of the hydrogen atoms availablefor ligand binding on the positive charge in ethanolamineions, due to overloading of the buffer gas with ethyl lactate.This ligand saturation deterred the attachment of addi-tional molecules of ethyl lactate, and no further decreasein the mobility of ethanolamine ions was obtained whenthe concentrations of ethyl lactate increased.Table 2 shows that there was a tendency towards large%ΔK0

values when the mass of the analyte decreased. For analyteswith relatively small steric hindrance on the positive charge,such as desipramine, serine, valinol, 2,4-lutidine, and ethanola-mine ions, the mass to %ΔK0 correlation coefficient was �0.91when the ethyl lactate concentration increased from 0.0 to1.7 mmol m–3 in the buffer gas. This inverse relationshipbetweenmass and%ΔK0 originated in the large increase of sizewith the attachment of modifier molecules to small analytes.Increased clustering was also expected as the size decreased,as a consequence of localization of the positive charge.[15,37]

Steric hindrance, of course, would obscure this mass-%ΔK0

trend by deterring clustering in spite of the size of the analyteions as found for TMA ions, which showed %ΔK0 values ofonly 1%, which were small compared with the values of 41and 37% for ethanolamine ions of similar mass.In summary, ion mobilities decreased (average %ΔK0

value of 9.1% for all the modifiers), due to the formation ofanalyte-modifier clusters. The mobilities of the DTBP andtetraalkylammonium ions showed only small changes (aver-age %ΔK0 value of 0.54% with ethyl lactate and nitrobenzenemodifiers) as a consequence of steric hindrance and chargedelocalization, which hindered clustering. In addition, ligandsaturation of binding sites limited the decrease in mobilityas a function of modifier concentration in the buffer gas.Finally, changes in ion mobility due to clustering were largefor low-mass ions.

Effect of intramolecular bridges on ion mobility

From Fig. 4 it can be seen that the mobility of the atenolol ionwas only slightly affected by the addition of a modifier to thebuffer gas. The atenolol ion was essentially unaffected by


the addition of 2-butanol to the buffer gas. Table 2 shows thatthe mobility was only slightly reduced on the addition of nitro-benzene. While the tetraalkylammonium ions, discussedabove, were essentially unaffected by the introduction of amodifier, the reduction in the mobility of the atenolol ionwas much less than that of many of the other analytes inves-tigated. This is most clearly demonstrated in Fig. 6 using amixture of desipramine and atenolol.

These drugs have the same nominal molecular weight(266 gmol–1) and, therefore, their mobilities are expected tobe affected to the same extent by clustering. Desipramine isan antidepressant and atenolol is a b-blocker drug used toprevent angina and to reduce the risk of heart attacks byreducing heart rate and high blood pressure. The IMS spectraof the mixture of these drugs show a small separation of thepeaks in N2-only buffer gas (Δtd= 0.8 ms, a=1.03) in Fig. 6(a);when 0.33 mmol m–3 of ethyl lactate was introduced intothe buffer gas, the separation increased (Δtd= 1.6 ms,a= 1.05, Fig. 6(b)) and when the ethyl lactate concentrationincreased to 1.7 mmol m–3, the separation increased evenmore (Δtd= 3.2 ms, a= 1.11, Fig. 6(c)).

Figures 6(d) and 6(e) provide an explanation of why themobility of atenolol ions was less affected than that ofdesipramine ions after the introduction of ethyl lactate intothe buffer gas. In these figures, the mass spectra of solutionsof desipramine and atenolol with 0.66 mmol m–3 of ethyllactate modifier in the buffer gas show that:

• The intensity of protonated desipramine (m/z 267) waslower than that of its cluster with ethyl lactate (m/z 385);for atenolol, however, the peak intensity of the protonatedmolecule (m/z 267) was stronger than that of the clusterwith ethyl lactate (m/z 385).

• A cluster of desipramine with two ethyl lactate moleculesoccurred at m/z 503, DL2.H

+, but not the cluster of atenololwith two ethyl lactate molecules, AL2.H

+ at m/z 503.

These two facts indicate a lower clustering of ethyl lactatewith atenolol ions than with desipramine ions.

The reduced interaction of atenolol ions with the modifiersmay be related to the formation of an intramolecular protonbridge between its two amine functionalities, as illustrated inFigs. 6(f) and 6(g). The access of ethyl lactate to the positivecharge of atenolol would be restricted by the ring on one sideand the isopropyl group on the opposite side when this bridgewas formed. Desipramine ions clustered more than atenololions because the formation of the intramolecular bridgein desipramine was sterically hindered due to the positionof one of the amine moieties between large aromatic rings(Fig. 6(h)). This steric hindrance to the formation of the bridgewould cause desipramine ions to adopt an open structure,prone to more collisions and clustering, which explains thelarger ion mobility change observed for this ion than forthe atenolol ion with ethyl lactate in the buffer gas. Sterichindrance to the formation of the proton bridge, similar tothat of desipramine ions, was observed in the ions of thediamine tryptophan, which also has an amine moiety as partof a ring. The tryptophan ion mobility also was affected bymodifiers in the buffer gas.[36]

Evidence for the ability of atenolol to form an intramolecu-lar proton bridge is that the mobility of the atenolol ion inthe pure nitrogen drift gas was higher than that of the


9

Figure 6. Clustering of desipramine and atenolol ions and intramolecularbridges. The drift time separation between desipramine and atenolol ionsincreased when the ethyl lactate concentration in the buffer gas was increasedfrom (a) 0, to (b) 0.33, and (c) 1.7 mmol m–3. (d, e) MS spectra of desipramine(D) and atenolol (A) at 150 �C when 0.66 mmol m–3 of ethyl lactate (L) wasintroduced into the buffer gas. (f) Structure and (g) 3D model of theformation of the bridge in atenolol: the arrow signals the hydrogen bridge. Thesteric hindrance and charge delocalization caused by the bridge deterred cluster-ing to ethyl lactate molecules. (h) 3D model of desipramine; an arrow shows thenitrogen between the aromatic rings which sterically hindered the formation ofthe bridge with the nitrogen in the alkyl chain. The models were generated usingthe program Chem3D Pro 11.0 (PerkinElmer Inc., Cambridge, MA, USA).


2220

desipramine ion although their masses are the same. Theformation of an intramolecular proton bridge would causethe ion structure to be more compact. The possibility ofthe formation of intramolecular proton bridges in diamineswas reported by Karpas who found that the mobilities ofa,o-diamines were higher than those of normal monoaminesas a consequence of a cyclization reaction between the twoamine moieties.[30]

Additional evidence of the formation of intramolecularproton bridges in diamines was obtained by studying basicamino acids. The mobilities of arginine, and histidine andlysine ions only decreased by 0.3 and 1.1%, respectively,when the 2-butanol concentration increased from 0.0 to6.8 mmol m–3 (2.5� 102 ppmv) in the buffer gas (Table 2).These changes in the %ΔK0 values of ions of basic aminoacids were small compared with the average value of10.2% for ions of non-basic amino acids such as methionine,serine, tryptophan, and tyrosine under similar experimentalconditions.[36] In addition, the mobility of arginine ionsonly decreased by 2.7% with 1.0 mmol m–3 of nitrobenzenein the buffer gas, which was small compared with the


%ΔK0 values of ethanolamine (37%) and valinol ions(21%) under the same conditions. Figure 7 shows themass spectra of arginine, histidine, and lysine when6.8 mmol m–3 (2.5� 102 ppmv) of 2-butanol (B) were intro-duced into the buffer gas. These basic amino acids pro-duced large MH+ ion peaks (HisH+ m/z 156, LysH+ 147,and ArgH+ 175) and only small analyte-2-butanol clusterpeaks (HisBH+ at m/z 230, LysBH+ at m/z 221, which wasoverlapped with the modifier trimer at m/z 223, andArgBH+ atm/z 249). The limited mobility shift of basic aminoacids to the introduction of modifiers into the buffer gasmay be related to this low clustering capacity. Figure 7(d)compares the high clustering of phenylalanine (Phe) withthe low clustering of basic amino acids with 2-butanol (B)modifier in the mass spectrum. The PheBH+ and PheB2H

+

clusters occurred at m/z 240 and 314. This lack of ion-modifier clustering of basic amino acids may be due to theformation of an intramolecular proton bridge between thetwo amine functionalities, deterring attachment of modifiermolecules to the positive charge of basic amino acids bysteric hindrance and charge delocalization.


Figure 7. Low clustering in basic amino acids. Mass spectra of (a) arginine, (b)histidine, and (c) lysine with 6.8 mmol m–3 (2.5� 102 ppmv) of 2-butanol (B) inthe buffer gas. Basic amino acids showed large MH+ peaks (ArgH+ m/z 175,HisH+ m/z 156, and LysH+ m/z 147) and only small analyte-modifier peaks(HisBH+ m/z 230, LysBH+ m/z 221, which was overlapped with the modifiertrimer at m/z 223, and ArgBH+ m/z 249) due to steric hindrance produced byan intramolecular bridge. (d) Mass spectrum of a 100-mM solution of phenylala-nine (Phe) at the same 2-butanol concentration as in (a–c); cluster peaks of 2-butanol were evident at m/z 149 (dimer), 223 (trimer), and 297 (tetramer), andthe clusters of phenylalanine with 2-butanol occurred at m/z 240 and 314.


222

Resolution of IMS overlapping ions by selective clustering

Application of drift gas modifiers to effect resolution in IMSwas demonstrated using differences in intramolecular protonbridging of diamines and monoamines (Fig. 8). Figure 8demonstrates the use of a buffer gas modifier, 2-butanol, toeffect the baseline resolution of partially overlapping ionpeaks. Figure 8(a) shows the IMS spectra of a mixture ofarginine (22.0 ms) and phenylalanine (22.5 ms), which partiallyoverlap inN2-only buffer gas. Figure 8(b) demonstrates that thetwo ions can be baseline-resolved by introducing 2-butanol as amodifier into the nitrogen buffer gas at a concentration of6.8 mmol m–3 (250 ppm v/v). In this case the addition of themodifier did not affect the mobility of the arginine ion but didreduce the mobility of the phenylalanine ion such that it eluted3.4 ms after the arginine ion, increasing the resolution of thesetwo ions from about 1.0 to about 8.5. This dramatic differencein mobility as a function of modifier addition was attributedto the ability of the arginine ion to form intramolecular protonbridges between the two amine groups while the amineprotons of the phenylalanine ion could interact with the modi-fier to produce phenylanlanine.H+(2butanol)n ion clusters.Mass spectral evidence for the formation of these clusters isgiven in Fig. 7.


A second example of separation is shown in Fig. 8(c)where the mobility of the isoleucine ion is reduced as afunction of modifier addition to the nitrogen buffer gas.The full IM spectrum in Fig. 8c shows the IMS separationof a mixture of the amino acids alanine, serine, threonine,isoleucine, and lysine. In this spectrum the isoleucine ionelutes before the lysine ion but is not completely separatedfrom it. The insert in Fig. 8(c) shows the baseline resolu-tion of lysine and isoleucine ions after the addition of6.8 mmol m–3 of 2-butanol to the nitrogen buffer gas. Withthe addition of 2-butanol the drift time of the isoleucineion increased by 1.2 ms but the drift time of the lysineion increased only by 0.2 ms, producing the separation ofthese two amino acids with a resolution of about 2.0. Aswith the arginine ion, in the example above, lysine hasthe ability to form intramolecular proton bridges whichapparently reduces its ability to cluster with 2-butanolwhile the isoleucine ion forms 2-butanol clusters thatincrease its size and reduce its mobility. Note: The separationof these amino acids could not be obtained at 250 �C (data notshown), perhaps because the decreased isoleucine-2-butanolinteractions at high temperature did not allow clusteringof isoleucine.


1

Figure 8. IMS separations by introducing 2-butanol into thebuffer gas. (a) IMS spectra (average of 1600) of a 100-mMmixtureof arginine (Arg) and phenylalanine (Phe) in N2-only buffer gasand (b)when 6.8mmolm–3 of 2-butanol (B)was injected into thebuffer gas. (c) IMS spectra (average of 1600) of a 50-mMmixtureof alanine (Ala), serine (Ser), threonine (Thr), isoleucine (Ile), andlysine (Lys) in N2-only buffer gas. The inset demonstrates theseparation of a mixture of lysine and isoleucine ions with6.8 mmol m–3 of 2-butanol (B) in the buffer gas. 2-Butanol madepossible the baseline resolution of these two pairs of ions byforming IleB and PheB clusters (shown in Fig. 7(d) for Phe),which reduced themobilities of Ile andPhe. The steric hindrancein arginine and lysine, caused by an intramolecular bridge,deterred extensive formation of clusters, and these amino acidmobilities were not affected by the modifier.


2222

CONCLUSIONS

Formation of ion-modifier clusters was found when liquidmodifiers such as ethyl lactate, nitrobenzene, tetrahydrofuran-2-carbonitrile, and 2-butanol were vaporized into the buffergas of an ion mobility spectrometer. Analytes clustered todifferent extents with a modifier, depending on their sizeand the formation of intramolecular bridges. Intramolecularbridges limited clustering in diamines by hindering theattachment of modifier molecules to the positive charge ofthose analytes, for which diamines only experienced smallchanges in ion mobilities with the addition of modifiers intothe buffer gas. Steric hindrance caused by bulky substituentsand large size also limited changes in ion mobility withmodifiers in the buffer gas. This difference in clusteringslowed down the ions with abundant clustering and onlyslightly affected the mobility of ions with limited clustering.These different clustering behaviors were applied to separationof mixtures of compounds that overlapped in IMS by selec-tively changing their ion mobilities. Modifiers also produceddifferent changes in mobilities: ethyl lactate had a larger effectthan nitrobenzene or 2-butanol on ion mobilities due to larger


formation of clusters. Finally, tetrahydrofuran-2-carbonitrilestripped off the charge of the analytes, except for those withsteric hindrance that deterred clustering, for which it wasconsidered to be inappropriate as a modifier for shifting drifttimes of ions. This selective charge stripping suggests apossible use of this modifier as a means of simplifying thespectra of complex mixtures of analytes.

AcknowledgementsThis work was supported by a grant from Excellims Corpora-tion (Acton, MA, USA) and NIH grant R33DK0702740351.The authors thank the WSU-GPWC for proofreading themanuscript.

REFERENCES

[1] F. W. Karasek, H. H. Hill, S. H. Kim. Plasma chromatogra-phy of heroin and cocaine with mass-identified mobilityspectra. J. Chromatogr. 1976, 117, 327.

[2] G. R. Asbury, J. Klasmeier, H. H. Hill Jr. Analysis of explo-sives using electrospray ionization/ion mobility spectrome-try (ESI/IMS). Talanta 2000, 50, 1291.

[3] H. Borsdorf, E. G. Nazarov, R. A. Miller. Time of flight ionmobility spectrometry and differential mobility spectrome-try: A comparative study of their efficiency in the analysisof halogenated compounds. Talanta 2007, 71, 1804.

[4] J. C. Oxley, J. L. Smith, L. J. Kirschenbaum, S. Marimganti,S. Vadlamannati. Detection of explosives in hair using ionmobility spectrometry. J. Forensic Sci. 2008, 53, 3, 690.

[5] M. T. Jafari, T. Khayamian, V. Shaer, N. Zarei. Determinationof veterinary drug residues in chicken meat using coronadischarge ion mobility spectrometry. Anal. Chim. Acta 2007,581, 147.

[6] N. Alizadeh, A. Mohammadi, M. Tabrizchi. Rapid screen-ing of methamphetamines in human serum by headspacesolid-phase microextraction using a dodecylsulfate-dopedpolypyrrole film coupled to ion mobility spectrometry. J.Chromatogr. A 2008, 1183, 21.

[7] M. A. Strege, J. Kozerski, N. Juarbe, P. Mahoney. At-linequantitative ion mobility spectrometry for direct analysisof swabs for pharmaceutical manufacturing equipmentcleaning verification. Anal. Chem. 2008, 80, 8, 3040.

[8] P. Dwivedi, B. Bendiak, B. H. Clowers, H. H. Hill Jr. Rapidresolution of carbohydrate isomers by electrospray ioniza-tion ambient pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS-TOFMS). J. Am. Soc.Mass Spectrom. 2007, 18, 7, 1163.

[9] J. A. Taraszka, X. Gao, S. J. Valentine, R. A. Sowell,S. L. Koeniger, D. F. Miller, T. C. Kaufman, D. E. Clemmer.Proteome profiling for assessing diversity: Analysis ofindividual heads of Drosophila melanogaster using LC-ionmobility-MS. J. Proteome Res. 2005, 4, 1238.

[10] C. S. Kaddis, S. H. Lomeli, S. Yin, B. Berhane, M. I. Apostol,V. A. Kickhoefer, L. H. Rome, J. A. Loo. Sizing large proteinsand protein complexes by electrospray ionization massspectrometry and ion mobility. J. Am. Soc. Mass Spectrom.2007, 18, 7, 1206.

[11] P. Dwivedi, P. Wu, S. J. Klopsch, G. J. Puzon, L. Xun,H. H. Hill Jr. Metabolic profiling by ion mobility mass spec-trometry (IMMS). Metabolomics 2008, 4, 63.

[12] X. Liu, S. J. Valentine, M. D. Plasencia, S. Trimpin, S. Naylor,D. E. Clemmer. Mapping the human plasma proteome bySCX-LC-IMS-MS. J. Am. Soc. Mass Spectrom. 2007, 18, 1249.



[13] R. M. O’Donnell, X. Sun, P. B. Harrington. Pharmaceuticalapplications of ion mobility spectrometry. Trends Anal.Chem. 2008, 27, 1, 44.

[14] A. B. Kanu, P. Dwivedi, M. Tam, L. M. Matz, H. H. Hill Jr. Ionmobility-mass spectrometry. J. Mass Spectrom. 2008, 43, 1.

[15] G. A. Eiceman, Z. Karpas, Ion Mobility Spectrometry, Taylor &Francis, Boca Raton, FL, USA, 2005.

[16] H. E. Revercomb, E. A. Mason. Theory of plasma chromato-graphy/ gaseous electrophoresis. Anal. Chem. 1975, 47, 970.

[17] R. T. Lattey. The effect of small traces of water vapour on thevelocities of ions produced by Röntgen rays in air. Proc. Roy.Soc. Lond. A 1910, 84, 569, 173.

[18] R. T. Lattey, H. T. Tizard. On the velocities of ions in driedgases. Proc. Roy. Soc. Lond. A 1912, 86, 588, 349.

[19] H. Gan, G. T. Corino. Selective detection of alkanolaminevapors by ion mobility spectrometry with ketone reagentgases. Anal. Chem. 2000, 72, 807.

[20] H. R. Bollan, J. A. Stone, J. L. Brokenshire, J. E. Rodriguez, G. A.Eiceman. Mobility resolution and mass analysis of ions fromammonia and hydrazine complexes with ketones formed inair at ambient pressure. J. Am. Soc.Mass Spectrom. 2007, 18, 940.

[21] P. Dwivedi, C. Wu, L. M. Matz, B. H. Clowers, W. F. Siems,H. H. Hill Jr. Gas-phase chiral separations by ion mobilityspectrometry. Anal. Chem. 2006, 78, 8200.

[22] S. H. Kim, F. W. Karasek, S. Rokushika. Anal. Chem. 1978,50, 152.

[23] G. E. Spangler, J. P. Carrico, D. N. Campbell. Recentadvances in ion mobility spectrometry for explosives vapordetection. J. Test Eval. 1985, 13, 234.

[24] C. J. Proctor, J. F. J. Todd. Alternative reagent ions for plasmachromatography. Anal. Chem. 1984, 56, 1794.

[25] D. A. Blyth. A vapor monitor for detection and contamina-tion control, in Proc. Int. Symp. Against Chemical WarfareAgents, Stockholm, 1983.

[26] G. A. Eiceman, Y. F. Wang, L. Garcia-Gonzalez, C.S. Harden,D.B. Shoff. Enhanced selectivity in ion mobility spectrome-try analysis of complex mixtures by alternate reagent gaschemistry. Anal. Chim. Acta 1995, 306, 21.


[27] G. A. Eiceman, M. R. Salazar, M. R. Rodriguez, T. F. Limero,S. W. Beck, J. H. Cross, R. Young, J. T. James. Ion mobilityspectrometry of hydrazine, monomethylhydrazine, andammonia in air with 5-nonanone reagent gas. Anal. Chem.1993, 65, 1696.

[28] Q. Meng, Z. Karpas, G. A. Eiceman. Monitoring indoorambient atmospheres for volatile organic compoundsusing an ion mobility analyzer array with selectivechemical ionization. Int. J. Environ. Anal. Chem. 1994,61, 81.

[29] J. Puton, M. Nousiainen, M. Sillanpaa. Ion mobility spectro-meters with doped gases. Talanta 2008, 76, 978.

[30] Z. Karpas. Evidence for proton-induced cyclization in abdiamines frommobility measurements. Int. J. Mass Spectrom.Ion Processes 1989, 93, 237.

[31] H. H. Hill Jr, G. Simpson. Capabilities and limitations of ionmobility spectrometry for field screening applications. J.Field Anal. Chem. Technol. 1997, 1, 119.

[32] C. Wu, W. F. Siems, G. R. Asbury, H. H. Hill. Electrosprayionization high-resolution ion mobility spectrometry-massspectrometry. Anal. Chem. 1998, 70, 4929.

[33] G. A. Eiceman, E. G. Nazarov, J. A. Stone. Chemical stan-dards in ion mobility spectrometry. Anal. Chim. Acta 2003,493, 185.

[34] R. Fernandez-Maestre, C. S. Harden, R. G. Ewing, C. L.Crawford, H. H. Hill. Chemical standards in ion mobilityspectrometry. Analyst 2010, 135, 1433.

[35] M. Tabrizchi, A. Abedi. A novel use of negative ion mobilityspectrometry for measuring electron attachment rates. J.Phys. Chem. A 2004, 108, 6319.

[36] R. Fernandez-Maestre, C. Wu, H. H. Hill. Using abuffer gas modifier to change separation selectivity inion mobility spectrometry. Int. J. Mass Spectrom. 2010,298, 2.

[37] J. Sunner, M. G. Ikonomou, P. Kebarle. Sensitivity enhance-ments obtained at high temperatures in atmosphericpressure ionization mass spectrometry. Anal. Chem. 1988,60, 1308.


2223

Buffer gas modifiers effect resolution in ion mobility spectrometry through selective ion-molecule...

Documents

Transcript of Buffer gas modifiers effect resolution in ion mobility spectrometry through selective ion-molecule...