Formic Acid as a Dopant for Atmospheric Pressure Chemical Ionization for Negative Polarity of Ion Mobility Spectrometry and Mass Spectrometry.

Formic acid (FA) is introduced as a potent dopant for atmospheric pressure chemical ionization (APCI) for ion mobility spectrometry (IMS) and mass spectrometry (MS). The mechanism of chemical ionization with the FA dopant was studied in the negative polarity using a corona discharge (CD)-IMS-MS technique in air. Standard reactant ions of the negative polarity present in air are O2-·(CO2)n·(H2O)m (m = 0, 1 and n = 1, 2) clusters. Introduction of the FA dopant resulted in the production of HCOO-·FA reactant ions. The effect of the FA dopant on the APCI of different classes of compounds was investigated, including plant hormones, pesticides, acidic drugs, and explosives. FA dopant APCI resulted in deprotonation and/or adduct ion formation, [M - H]- and [M + HCOO]-, respectively. Supporting density functional theory (DFT) calculations showed that the ionization mechanism depended on the gas-phase acidity of the compounds. FA dopant APCI led to the improvement of detection sensitivity, suppression of fragmentation, and changes in the ion mobilities of the analyte ions for analytes with suitable molecular structures and gas acidity.

Solid Phase Microextraction-Multicapillary Column-Ion Mobility Spectrometry (SPME-MCC-IMS) for Detection of Methyl Salicylate in Tomato Leaves.

Methyl salicylate (MeSA) is a plant-signaling molecule that plays an essential role in the regulation of plant responses to biotic and abiotic pathogens. In this work, solid phase microextraction (SPME) and a multicapillary column (MCC) are coupled to ion mobility spectrometry (IMS) to detect MeSA in tomato leaves. The SPME-MCC-IMS method provides two-dimensional (2D) separation by both MCC and IMS, based on the retention and drift times. The effect of the IMS polarity on the separation efficiency of MCCs was also investigated. In the positive polarity, ionization of MeSA resulted in [MeSA + H]+ formation while, in the negative, deprotonated ions, [MeSA - H]-, and the O2- adduct ion, [MeSA + O2]-, were formed. In the real sample analysis, the negative polarity operation resulted in the suppression of many matrix molecules and thus in the reduction of interferences. Four different SPME fibers were used for head space analysis, and four MCC columns were investigated. In the negative polarity, complete separation was achieved for all of the MCCs columns. The limits of detection (LODs) of 0.1 µg mL-1 and linear range of 0.25-12 µg mL-1 were obtained for the measurement of MeSA in a standard solution (H2O/CH3OH, 50:50) by the SPME-IMS method with a 5 min extraction time using an SPME with a PDMS fiber, in the negative mode of IMS. The MeSA contents of fresh tomato leaves were determined as 1.5-9.8 µg g-1, 24-96 h after inoculation by tomato mosaic ringspot virus (ToRSV).

Effect of ion source polarity and dopants on the detection of auxin plant hormones by ion mobility-mass spectrometry.

Ion mobility spectrometry (IMS) equipped with a corona discharge (CD) ion source was used for measurement of three auxin plant hormones including indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), and indole-3-butyric acid (IBA). The measurements were performed in both positive and negative polarities of the CD ion source. Dopant gases NH3, CCl4, and CHBr3 were used to modify the ionization mechanism. A time-of-flight mass spectrometer (TOFMS) orthogonal to the IMS cell was used for identification of the product ions. Density functional theory was used to rationalize formation of the ions, theoretically. The mixtures of the auxins were analyzed by CD-IMS. The separation performance depended on the ion polarity and the dopants. In the positive polarity without dopants, auxins were ionized via protonation and three distinguished peaks were observed. Application of NH3 dopant resulted in two ionization channels, protonation, and NH4+ attachment leading to peak overlapping. In the negative polarity, two ionization reactions were operative, via deprotonation and O2- attachment. The separation of the monomer peaks was not achieved while the peaks of anionic dimers [2 M-H]- were separated well. The best LOD (4 ng) was obtained in negative polarity with CCl4 dopant. Methylation (esterification) of IAA improved LODs by about one order.

Rapid and simple determination of gabapentin in urine by ion mobility spectrometry.

Gabapentin is a pharmacological agent used in the treatment of epileptic seizures. In this work, a fast method is proposed for determination of gabapentin in urine by ion mobility spectrometry (IMS) without any extraction and derivatization. ZnCl2 was used as an effective protein precipitating reagent to remove the urine proteins. It was found that urea content of urine interferes with detection of gabapentin by IMS. By applying a delay on the carrier gas flow after injection of the sample, we could solve the urea interference to achieve gabapentin signal recovery of ∼70% in urine relative to that in water.

Using gas-phase chloride attachment for selective detection of morphine in a morphine/codeine mixture by ion mobility spectrometry.

RATIONALE: Morphine and codeine are two important compounds of the opiate family that have vast applications in medicine. Several techniques have been reported for the determination of these opiates. Although ion mobility spectrometry (IMS) in positive ion mode can be applied for detection of both morphine and codeine, this technique on its own cannot detect a mixture of these two compounds because of the overlapping of their peaks. METHODS: An IMS instrument equipped with a corona discharge ion source operating in negative ion mode was used for the detection of anionic clusters of morphine and codeine. In normal negative ion mode, NOx - , CO3 - , and On - act as the main reactant ions (RIs) which can deprotonate the analytes. We also used chloroform as a dopant to produce Cl- as an alternative RI. RESULTS: Morphine has a phenolic and an alcoholic OH group, while codeine bears only an alcoholic OH group. Because the phenolic OH group is more acidic, only morphine is deprotonated in negative ion mode in a morphine/codeine mixture. Furthermore, since morphine has two OH groups that can act as hydrogen-bond donors, it acts as an anion receptor. Hence, in the presence of chloroform where Cl- acts as the RI, morphine traps the Cl- anion to form a morphine-Cl- (Mor.Cl- ) adduct ion, while because of its structure codeine does not have this capability. CONCLUSIONS: Using the difference in the structures of morphine and codeine, two ionization methods were proposed for selective detection of morphine. Morphine is more acidic than codeine and has greater anion-receiving capability than codeine. Hence, it can both be deprotonated and form a adduct anion with Cl- . The Cl- attachment method is recommended for measurements at ambient temperature.

Online detection and measurement of elemental mercury vapor by ion mobility spectrometry with chloroform dopant.

A rapid and simple method is proposed for detection of elemental mercury (Hg) vapor by ion mobility spectrometry (IMS). Negative corona discharge (CD) as the ionization source and chloroform as the dopant gas were used to produce Cl- reactant ion. A mass spectrum of the product ions confirmed that the mechanism of ionization is based on Cl- anion attachment to Hg and formation of HgCl- ion. It was found that the optimum drift gas temperature for Hg detection was about 160 °C and the drift gas flow rate should be minimized and just sufficient to clear contaminants and carry-over from the drift cell. The drift time of the HgCl- peak relative to that of the Cl- peak at 160 °C is 1.52 ms corresponding to the reduced mobility of 1.90 cm2/Vs. Because many volatile organic compounds (VOCs) such as alcohols, amines, aldehydes, ketones, and alkanes are not ionized in the negative mode of CD-IMS, these compounds do not interfere with the detection of Hg. Mercaptans peaks also did not show any interference with the Hg signal. Hence, the method is highly selective for detection of Hg in natural gas containing sulfur compounds. The detection limit of Hg obtained by the proposed method was 0.07 mg/m3. The method was successfully verified in determination of the mercury vapor content of a fluorescent lamp, as a real sample.

Mechanism of atmospheric pressure chemical ionization of morphine, codeine, and thebaine in corona discharge-ion mobility spectrometry: Protonation, ammonium attachment, and carbocation formation.

Atmospheric pressure chemical ionizations (APCIs) of morphine, codeine, and thebaine were studied in a corona discharge ion source using ion mobility spectrometry (IMS) at temperature range of 100°C-200°C. Density functional theory (DFT) at the B3LYP/6-311++G(d,p) and M062X/6-311++G(d,p) levels of theory were used to interpret the experimental data. It was found that in the presence of H3 O+ as reactant ion (RI), ionization of morphine and codeine proceeds via both the protonation and carbocation formation, whereas thebaine participates only in protonation. Carbocation formation (fragmentation) was diminished with decrease in the temperature. At lower temperatures, proton-bound dimers of the compounds were also formed. Ammonia was used as a dopant to produce NH4 + as an alternative RI. In the presence of NH4 + , proton transfer from ammonium ion to morphine, codeine, and thebaine was the dominant mechanism of ionization. However, small amount of ammonium attachment was also observed. The theoretical calculations showed that nitrogen atom of the molecules is the most favorable proton acceptor site while the oxygen atoms participate in ammonium attachment. Furthermore, formation of the carbocations is because of the water elimination from the protonated forms of morphine and codeine.

A Novel Application of Dopants in Ion Mobility Spectrometry: Suppression of Fragment Ions of Citric Acid.

Ion mobility spectra of citric acid (CA) are complex, and several peaks are observed for CA and its fragments in both the positive and negative modes. Using DFT calculations, we found that the fragments are both less acidic and less basic than CA in gas phase. Hence, we used a strong base, NH3, in positive mode to produce NH4+ as an alternative reactant ion (RI) and prevent protonation of the fragments. In the presence of NH4+, only one peak for CA was observed because of its higher proton affinity (873 kJ mol-1) compared to NH3 (854 kJ mol-1). In the negative mode, CHCl3, CHBr3, and CHI3 were used as dopant gases to produce Cl-, Br-, and I- as RIs. These halides have less basicity than the common RIs in negative mode (NO2-, NO3-, O2-) and selectively deprotonated CA in the presence of its fragments. Hence, using dopants with appropriate basicity, we could suppress the fragment peaks and obtain a plain IMS spectrum for CA containing only one peak in both the positive and negative modes. Using NH3 and CHCl3 dopants, the amount of CA in fresh lemon juice was determined as 39.5-42 g L-1 by direct injection without any purification. The effect of hydration of the reactant and product ions on the ionization mechanism in both negative and positive modes was investigated theoretically.

Small Host-Guest Systems in the Gas Phase: Tartaric Acid as a Host for both Anionic and Cationic Guests in the Atmospheric Pressure Chemical Ionization Source of Ion Mobility Spectrometry.

The ionization of tartaric acid (TA) in an atmospheric pressure chemical ionization corona discharge ion source was studied by ion mobility spectrometry (IMS) with zero air as the drift gas. Density functional theory was used for structural and thermodynamic analyses of the produced ionic clusters. Ion mobility spectra of TA were recorded in both positive and negative modes of CD with and without ammonia and chloroform as dopants in order to produce NH4+ and Cl-, respectively, as the reactant ions (RIs). In the absence of these dopants, the RIs were mainly H3O+ and O2- in the positive and negative CD, respectively. TA solutions in water and methanol were injected into the ionization region of the IMS instrument, and the product cations TA·H+(H2O)n, TA·H+(CH3OH), TA·NH4+, and TA·NH4+(CH3OH) were observed in the positive CD. Anionic clusters (TA-H)-, (TA-H)-·CH3OH, (TA-H)-·TA, TA·Cl-, and (TA)2Cl- were produced in the negative CD. The anions TA·Cl- and (TA)2Cl- were not produced in an air atmosphere, and we observed their peaks when pure oxygen was used as the drift gas. Optimized structures of the clusters showed that TA·NH4+, TA·Cl-, and (TA)2Cl- are small host-guest systems in the gas phase, with TA as a host. (TA)2Cl- is a weakly bonded complex (an anion-bound dimer) that was observed at atmospheric pressure. The proton-bound dimer TA·H+·TA was not produced in the positive CD, while the anionic dimer (TA-H)-·TA was observed in the negative CD. This phenomenon was interpreted on the basis of the hydration of TA·H+ and (TA-H)-.

Effect of Basicity and Structure on the Hydration of Protonated Molecules, Proton-Bound Dimer and Cluster Formation: An Ion Mobility-Time of Flight Mass Spectrometry and Theoretical Study.

Protonation, hydration, and cluster formation of ammonia, formaldehyde, formic acid, acetone, butanone, 2-ocatanone, 2-nonanone, acetophenone, ethanol, pyridine, and its derivatives were studied by IMS-TOFMS technique equipped with a corona discharge ion source. It was found that tendency of the protonated molecules, MH+, to participate in hydration or cluster formation depends on the basicity of M. The molecules with higher basicity were hydrated less than those with lower basicity. The mass spectra of the low basic molecules such as formaldehyde exhibited larger clusters of MnH+(H2O)n, while for compounds with high basicity such as pyridine, only MH+ and MH+M peaks were observed. The results of DFT calculations show that enthalpies of hydrations and cluster formation decrease as basicities of the molecules increases. Using comparison of mass spectra of formic acid, formaldehyde, and ethanol, effect of structure on the cluster formation was also investigated. Formation of symmetric (MH+M) and asymmetric proton-bound dimers (MH+N) was studied by ion mobility and mass spectrometry techniques. Both theoretical and experimental results show that asymmetric dimers are formed more easily between molecules (M and N) with comparable basicity. As the basicity difference between M and N increases, the enthalpy of MH+N formation decreases.

Study of Atmospheric Pressure Chemical Ionization Mechanism in Corona Discharge Ion Source with and without NH3 Dopant by Ion Mobility Spectrometry combined with Mass Spectrometry: A Theoretical and Experimental Study.

Ionization of 2-nonanone, cyclopentanone, acetophenone, pyridine, and di- tert-butylpyridine (DTBP) in a corona discharge (CD) atmospheric pressure chemical ionization (APCI) ion source was studied using ion mobility (IMS) and time-of-flight mass spectrometry (TOF-MS). The IMS and MS spectra were recorded in the absence and presence of ammonia dopant. Without NH3 dopant, the reactant ion (RI) was H+(H2O) n, n = 3,4, and the MH+(H2O) x clusters were produced as product ions. Modeling of hydration shows that the amount of hydration ( x) depends on basicity of M, temperature and water concentration of drift tube. In the presence of ammonia (NH4+(H2O) n as RI) two kinds of product ions, MH+(H2O) x and MNH4+(H2O) x, were produced, depending on the basicity of M. With NH4+(H2O) n as RI, the product ions of pyridine and DTBP with higher basicity were MH+(H2O) x while cyclopentanone, 2-nonanone, and acetophenone with lower basicity produce MNH4+(H2O) x. To interpret the formation of product ions, the interaction energies of M-H+, H+-NH3, and H+-OH2 in the M-H+-NH3 and M-H+-OH2 and M-H+-M complexes were computed by B3LYP/6-311++G(d,p) method. It was found that for a molecule M with high basicity, the M-H+ interaction is strong leading in weakening of the H+-NH3, and H+-OH2 interactions in the M-H+-NH3 and M-H+-OH2 complexes.

Laser desorption-ion mobility spectrometry as a useful tool for imaging of thin layer chromatography surface.

We present a novel method for coupling thin layer chromatography (TLC) with ion mobility spectrometry (IMS) using laser desorption technique (LD). After separation of the compounds by TLC, the TLC surface was sampled by the LD-IMS without any further manipulation or preparation. The position of the laser was fixed and the TLC plate was moved in desired directions by the motorized micro-positioning stage. The method was successfully applied to analyze the TLC plates containing explosives (tri nitro toluene, 1,3,5-trinitro- 1,3,5-triazacyclohexane, pentaerythritol tetranitrate, 2,4-dinitro toluene and 3,4-dinitro toluene), amino acids (alanine, proline and isoleucine), nicotine and diphenylamine mixtures and detection limits for these compounds were determined. Combination of TLC with LD-IMS technique offers additional separation dimension, allowing separation of overlapping TLC analytes. The time for TLC sampling by LD-IMS was less than 80s. The scan rate for LD is adjustable so that fast and effective analysis of the mixtures is possible with the proposed method.

Ion Mobility Spectrometry of Heavy Metals.

A simple, fast, and inexpensive method was developed for detecting heavy metals via the ion mobility spectrometry (IMS) in the negative mode. In this method, Cl(-) ion produced by the thermal ionization of NaCl is employed as the dopant or the ionizing reagent to ionize heavy metals. In practice, a solution of mixed heavy metals and NaCl salts was directly deposited on a Nichrome filament and electrically heated to vaporize the salts. This produced the IMS spectra of several heavy-metal salts, including CdCl2, ZnSO4, NiCl2, HgSO4, HgCl2, PbI2, and Pb(Ac)2. For each heavy metal (M), one or two major peaks were observed, which were attributed to M·Cl(-) or [M·NaCl]Cl(-)complexes. The method proved to be useful for the analysis of mixed heavy metals. The absolute detection limits measured for ZnSO4 and HgSO4 were 0.1 and 0.05 µg, respectively.

Thin layer chromatography-ion mobility spectrometry (TLC-IMS).

Ion mobility spectrometry (IMS) is a fast and sensitive analytical method which operates at the atmospheric pressure. To enhance the capability of IMS for the analysis of mixtures, it is often used with preseparation techniques, such as GC or HPLC. Here, we report for the first time the coupling of the thin-layer chromatography and IMS. A variety of coupling schemes were tried that included direct electrospray from the TLC strip tip, indirect electrospray from a needle connected to the TLC strip, introducing the moving solvent into the injection port, and, the simplest way, offline introduction of scratched or cut pieces of strips into the IMS injection port. In this study a special solvent tank was designed and the TLC strip was mounted horizontally where the solvent would flow down. A very small funnel right below the TLC tip collected the solvent and transferred it to a needle via a capillary tubing. Using the TLC-ESI-IMS technique, acceptable separations were achieved for two component mixtures of morphine-papaverine and acridine-papaverine. A special injection port was designed to host the pieces cut off the TLC. The method was successfully used to identify each spot on the TLC by IMS in a few seconds.

Using corona discharge-ion mobility spectrometry for detection of 2,4,6-Trichloroanisole.

In this work possible application of the corona discharge-ion mobility spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been investigated. We applied CD-IMS interfaced with orthogonal acceleration time of flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD-IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and (ii) reverse flow modes resulting in different chemical ionisation schemes by NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA. The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl) adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and solid phases (150 ng).

Peak-peak repulsion in ion mobility spectrometry.

The space charge effect has an important role in instruments dealing with ion packets and charged particles in gas phase such as the mass spectrometer and ion mobility spectrometer (IMS). It has been shown that the space charge is partially responsible for peak broadening in IMS depending on the ion density. Here, we explore the effect of space charge on peak shifting in IMS. We show that the field created by a large peak influences the drift time of a neighboring small peak. An experimental method was introduced to accurately measure the effect of space charge between two peaks. In this method, a double pulse was applied to the shutter grid to create two closed ion packets with a given initial spacing. The final spacing was then measured at the collector through the separation of the two peaks. This study shows that space charge repulsion must be considered for accurate measurements of ion mobilities. The experiments were performed in both normal and inverse modes. A theoretical model was also proposed to describe the repulsion between two ion packets in IMS.

Detection of explosives by positive corona discharge ion mobility spectrometry.

In this work, thermal decomposition has been used to detect explosives by IMS in positive polarity. Explosives including Pentaerythritol Tetranitrate (PETN), Cyclo-1,3,5-Trimethylene-2,4,6-Trinitramine (RDX), 2,4,6-Trinitrotoluene (TNT), 2,4-Dihydro-5-nitro-3H-1,2,4-triazol-3-one (NTO), 1,3,5,7-Tetranitro-1,3,5,7-tetrazocine (HMX), have been evaluated at temperatures between 150 and 250 degrees C in positive polarity in air. Explosives yield NO(x) which causes NO(+) peak to increase. Additional peaks may be used to identify the type of explosive. The limit of detection for RDX, HMX, PETN, NTO, and TNT were obtained to be 1, 10, 40, 1000, and 1000 ng, respectively.