Predicting Compensation Voltage for Singlycharged

Authors: Alexander A Aksenov James Kapron Cristina E Davis

Publish Date: 2012/08/08

Volume: 23, Issue: 10, Pages: 1794-1798

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Abstract

Correlation between compensation voltage CV and the m/z ratio of singlycharged ions was elucidated The experimental data for various alkylammonium homologues and various pharmaceutical compounds were used to construct empirical calibration curves that were fit using commercial regression analysis software packages The best fit equations were applied to calculate the CV differences ΔCV in pure N2 and N2/He 50/50 carrier gasses and CV values for a variety of compounds using only m/z values The calculated values were in good agreement with experimental data and ΔCV values exhibited a very strong correlation with m/z Application of these empirical calculations may provide a powerful CV prediction tool for researchers using highfield asymmetric waveform ion mobility spectrometry FAIMS and increase the value of FAIMS as an analytical methodThe technology of highfield asymmetric waveform ion mobility spectrometry FAIMS often called Differential Mobility Spectrometry DMS 1 originated in the USSR during the early 1980s 2 FAIMS/MS is able to resolve smallmolecule signals from nearlyisobaric interferences and it reduces the chemical noise generated in the ion source of a mass spectrometer improving selectivity and quantitative accuracy 3 The technology exploits differences in ion mobility at high and low electric fields 4 A DC potential called a compensation voltage CV is applied to a FAIMS electrode to compensate for ion drift under varying field conditions and allow a subset of ions to pass through the device The CV value reflects an ion’s properties as it relates to mobility under differential field conditions and therefore is unique to each ion The CV values can be used to identify certain ions or to allow ion filtering in a FAIMS device prior to introduction into the MS 5 However challenges arise in linking CV values to ion identities In particular it is not always possible to predict an ion’s CV The difficulty is mainly due to nonlinear dependence of the ion’s mobility with the field strength which is not always known for an ion/gas combinationPreviously successful attempts have been made to design an appropriate waveform and predict the CV for simple ions 6 7 For the majority of ions in a single buffer gas or in gas mixtures such predictions are not possible because the dependence of mobility on the electric field strength is not known For practical applications it is customary to infuse a pure standard and ramp the CV to experimentally determine the compound’s corresponding CV For subsequent FAIMS experiments most often as FAIMS/MS or LC/FAIMS/MS the CV is then set for the previously determined conditions For example in drug metabolism studies researchers would like to exclude chemical noise but be assured that all metabolites will be included If the CV values of metabolites are not known such an experiment will require scanning of the entire CV space prolonging the FAIMS scan and affecting total duty cycleCertain system designs allow for short ion residence times within the FAIMS device which enables faster waveform scans 8 For designs of FAIMS devices where fast scan is not possible the best way to increase throughput is to estimate the CV values prior to the experiment and then scan only the informative part of the CV space The prediction of CV is the major intellectual challenge to the successful application of this technology in the modern laboratoryIt is known that ion mobility correlates with ion size however the correlation to the ion mass or m/z is generally weaker for differential mobility ΔK than for K ie FAIMS is more orthogonal to MS than conventional IMS 9 10 It was also shown with the use of buffer gas modifiers 11 that complexation plays a certain role in the order of emergence and resolution of ions within FAIMS systems In general reports of correlation of CV and m/z are scarce and sometimes conflicting For example for CV–m/z correlations for triazine pollutant compounds 12 and in homologues series of lipids 13 have opposing trends reportedIn the present work we take the approach that upon elimination of complicating factors such as solvation CV values for singlycharged “reference” ions can be used to create a plot of CV and ΔCV versus m/z Unknown ΔCV and CV values for other compounds can then be determined based solely upon m/z of ionsAll chemicals were purchased from Sigma Aldrich Gillingham UK The pharmaceuticals were codeine terfenadine reserpine and erythromycin ethyl succinate The amine compounds were triethylamine NNdimethylbutylamine NNdimethylhexylamine tetramethyl ammonium bromide hexadecyltrimethylammonium bromide and ethanolamine The tetraalkyl ammonium halides TAA compounds were NR4X where R = methyl ethyl npropyl nbutyl npentyl nhexyl nheptyl noctyl and ndecyl and X = Br I The drift time ion mobility spectrometry DT IMS calibrants for positive ion were dimethyl methylphosphonate DMMP and lutidine DT IMS calibrants for negative ions were taurocholic acid and dipropylene glycol DPG In addition the FAIMS system performance check compounds polytyrosine 1 3 and 6isomers supplied along with the FAIMS system by Thermo Fisher Scientific San Jose CA USA were used HPLCgrade acetonitrile ACN methanol MeOH and formic acid were obtained from commercial sources and used without further purification Industrial grade gases and deionized water were used throughoutStock solutions of each compound were prepared by weighing the material and dissolving in ACN to 1 mg/mL Combined solutions of the TAAs were prepared by mixing individual TAA solutions The FAIMS/MS analysis is described in detail elsewhere 14 All the experiments were conducted using direct ESI infusion at 5 μL/min flow rate The FAIMS/MS system TSQ Quantum Ultra Thermo Fisher Scientific San Jose CA USA recommended standard conditions were used throughout positive ions dispersion voltage DV –5 kV 35 L/min equimolar nitrogen and helium carrier gas inner electrode temperature 70 °C and outer electrode temperature 90 °C Heated electrospray ionization HESI parameters were set as follows ion spray voltage 4000 V vaporizer temperature 400 °C tube lens offset 100 V

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