Secondary electrospray ionization-ion mobility spectrometry for explosive vapor detection

The unique capability of secondary electrospray ionization (SESI) as a nonradioactive ionization source to detect analytes in both liquid and gaseous samples was evaluated using aqueous solutions of three common military explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG) and pentaerythritol tetranitrate (PETN). The adducts formed between the compounds and their respective dissociation product, RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-), gave the most intense signal for the individual compound but were more sensitive to temperature than other species. These autoadducts were identified as RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-) and had maximum signal intensity at 137, 100, and 125 degrees C, respectively. The reduced mobility values of the three compounds were constant over the temperature range from 75 to 225 degrees C. The signal-to-noise ratios for RDX, NG, and PETN at 50 mg L(-1) in methanol-water were 340, 270, and 170, respectively, with a nominal noise of 8 +/- 2 pA. In addition to the investigation of autoadduct formation, the concept of doping the ionization source with nonvolatile adduct-forming agents was investigated and described for the first time. The SESI-IMS detection limit for RDX was 116 microg L(-1) in the presence of a traditional volatile chloride dopant and 5.30 microg L(-1) in the presence of a nonvolatile nitrate dopant. In addition to a lower detection limit, the nitrate dopant also produced a greater response sensitivity and a higher limit of linearity than did the traditional volatile chloride dopant.     

Coronaspray nebulization and ionization of liquid samples for ion mobility spectrometry

Ion mobility spectrometry after electrospray nebulization and ionization was investigated as a method for the detection of components dissolved in liquids. While electrosprary operating conditions proved promising, greater sensitivity was achieved when the electric potential applied to the sample introduction needle was increased above breakdown potential and a corona discharge was established. Passing the liquid through the corona discharge established a "coronaspray" that efficiently nebulized and ionized the solvent and analytes. In this initial investigation of coronaspray ion mobility spectrometry (CIMS), ion current as a function of potential, temperature, and liquid flow rate was studied; several IMS spectra were obtained; and a continuous monitoring mode of operation was demonstrated. The results from this study indicated that CIMS has potential as a versatile and sensitive detection method for a variety of analytical procedures involving liquid flowing streams such as flow injection analysis, liquid chromatography, capillary zone electrophoresis, and field flow fractionation.     

Gas-phase chiral separations by ion mobility spectrometry

This article introduces the concept of chiral ion mobility spectrometry (CIMS) and presents examples demonstrating the gas-phase separation of enantiomers of a wide range of racemates including pharmaceuticals, amino acids, and carbohydrates. CIMS is similar to traditional ion mobility spectrometry, where gas-phase ions, when subjected to a potential gradient, are separated at atmospheric pressure due to differences in their shapes and sizes. In addition to size and shape, CIMS separates ions based on their stereospecific interaction with a chiral gas. In order to achieve chiral discrimination by CIMS, an asymmetric environment was provided by doping the drift gas with a volatile chiral reagent. In this study (S)-(+)-2-butanol was used as a chiral modifier to demonstrate enantiomeric separations of atenolol, serine, methionine, threonine, methyl alpha-glucopyranoside, glucose, penicillamine, valinol, phenylalanine, and tryptophan from their respective racemic mixtures.     

Selective detection of alkanolamine vapors by ion mobility spectrometry with ketone reagent gases

The ion mobility (IMS) spectra of the alkanolamines, monoethanolamine (MEA), 3-amino-1-propanol (PRA), 4-amino-1-butanol (BUA), and 5-amino-1-pentanol (PEA) with acetone and 4-heptanone reagent gases have been measured using a hand-held spectrometer. Monomer and dimer peak patterns were observed for all the alkanolamines with acetone reagent gas. Drift times of monomer and dimer ion clusters for each alkanolamine increased linearly in order of size of alkyl group. Ammonia, Freon 22, and F76 diesel vapors, having similar or coincident mobilities, caused severe interference. Replacement of acetone with 4-heptanone reagent gas resulted in good separation by the altering drift times of product ions. The limit of detection was 0.005 ppm having a linear range of 0.005-0.7 ppm, and signal saturation occurred above 0.88 ppm. Detection was reversible, with a response time of 4 min and a slower recovery time of > 60 min, at vapor levels of 0.7 ppm and ambient nozzle and drift-region temperatures. In contrast to acetone chemistry, single-peak patterns were observed for the alkanolamines with the 4-heptanone reagent. Further, drift times unexpectedly remained stagnant with increasing alkyl-group size. From atmospheric pressure chemical ionization (APcI) tandem mass spectral identifications and collision induced studies, dynamic changes in product-ion equilibria in the IMS drift region compensated by differences in collision cross sections were suggested as the governing causes of the unusual mobility effect.     

Determination of parabens in pharmaceutical formulations by solid-phase microextraction-ion mobility spectrometry

Solid-phase microextraction (SPME) coupled with ion mobility spectrometry (IMS) was used for the detection and quantitation of 4-hydroxybenzoate preservatives, methylparaben, ethylparaben, propylparaben, and butylparaben, in commercial pharmaceutical products. For the first time, SPME-IMS is described for the simultaneous detection, separation, and quantitation of multiple analytes in complex matrixes. The parabens are extracted from the samples using SPME, and the analytes on the fiber are heated by the IMS desorber unit and vaporized into the drift tube. The four preservatives differing only by a methyl group were separated in less than 18 ms. The analytical procedure was optimized for fiber coating selection, extraction time, sample pH, sample volume, ionic strength, and IMS conditions. Separation characteristics such as resolution, theoretical plates, and drift times of the parabens were also evaluated based on the direct interfacing of SPME to IMS. The conditions were tested using six over-the-counter topical products containing various combinations of preservatives. Analysis of the samples by SPME-IMS using benzyl paraben as an internal standard yields good comparison to an HPLC method, thereby reinforcing the applicability of this technique as a method for routine analysis. Limits of detection were 10 ng/mL for methylparaben and ethylparaben and 5 ng/mL for propylparaben and butylparaben. Good linearity range and reproducibility of less than 8% were obtained.     

Interfacing an ion mobility spectrometry based explosive trace detector to a triple quadrupole mass spectrometer

Hardware from a commercial-off-the-shelf (COTS) ion mobility spectrometry (IMS) based explosive trace detector (ETD) has been interfaced to an AB/SCIEX API 2000 triple quadrupole mass spectrometer. To interface the COTS IMS based ETD to the API 2000, the faraday plate of the IMS instrument and the curtain plate of the mass spectrometer were removed from their respective systems and replaced by a custom faraday plate, which was fabricated with a hole for passing the ion beam to the mass spectrometer, and a custom interface flange, which was designed to attach the IMS instrument onto the mass spectrometer. Additionally, the mass spectrometer was modified to increase the electric field strength and decrease the pressure in the differentially pumped interface, causing a decrease in the effect of collisional focusing and permitting a mobility spectrum to be measured using the mass spectrometer. The utility of the COTS-ETD/API 2000 configuration for the characterization of the gas phase ion chemistry of COTS-ETD equipment was established by obtaining mass and tandem mass spectra in the continuous ion flow and selected mobility monitoring operating modes and by obtaining mass-selected ion mobility spectra for the explosive standard 2,4,6 trinitrotoluene (TNT). This analysis confirmed that the product ion for TNT is [TNT - H](-), the predominant collision-induced dissociation pathway for [TNT- H](-) is the loss of NO and NO(2), and the reduced mobility value for [TNT - H](-) is 1.54 cm(2)V(-1) s(-1). Moreover, this analysis was attained for sample amounts of 1 ng and with a resolving power of 37. The objective of the research is to advance the operational effectiveness of COTS IMS based ETD equipment by developing a platform that can facilitate the understanding of the ion chemistry intrinsic to the equipment.     

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.     

Characterization of benzodiazepine drugs by ion mobility spectrometry

Chemical ionization ion mobility spectrometry (CI-IMS) was used to characterize a number of benzodiazepines. In almost every example studied, the positive ion mobility spectrum consisted of a single ion peak corresponding to [M]+ or [MH]+. With some compounds, e.g., oxazepam, lorazepam, and chlordiazepoxide, fragment ions were noted that serve as good markers for the identification of these chemicals. Reduced mobility constants (K0) for the most significant peaks were calculated, and all ions produced were mass-analyzed by injection into a quadrupole mass spectrometer. The results of this study point to the potential of IMS as a qualitative tool for the rapid detection (analysis time less than 10 s) and reliable identification of benzodiazepines. Preliminary results on the application of digital signal processing and a second-derivative algorithm to partially overlapping IMS peaks are presented, and potential improvements are discussed.     

Distortion of ion structures by field asymmetric waveform ion mobility spectrometry

Field asymmetric waveform ion mobility spectrometry (FAIMS) is emerging as a major analytical tool, especially in conjunction with mass spectrometry (MS), conventional ion mobility spectrometry (IMS), or both. In particular, FAIMS is used to separate protein or peptide conformers prior to characterization by IMS, MS/MS, or H/D exchange. High electric fields in FAIMS induce ion heating, previously estimated at <10 degrees C on average and believed too weak to affect ion geometries. Here we use a FAIMS/IMS/MS system to compare the IMS spectra for ESI-generated ubiquitin ions that have and have not passed FAIMS and find that some unfolding occurs for most charge states. These data and their comparison with the reported protein unfolding in a Paul trap imply that at least some structural transitions observed in FAIMS, or previously in an ion trap, are not spontaneous. The observed unfolding is similar to that produced by heating of approximately 50 degrees C above room temperature, consistent with the calculated heating of ions at FAIMS waveform peaks. Hence, the ion isomerization in FAIMS likely proceeds in steps during the "hot" periods, especially right after entering the device. The process distorts ion geometries and causes ion losses by a "self-cleaning" mechanism and thus should be suppressed as much as possible. We propose achieving that via cooling FAIMS by the amount of ion heating; in most cases, cooling by approximately 75 degrees C should suffice.     

Cloud point extraction and flame atomic absorption spectrometry combination for copper(II) ion in environmental and biological samples

A cloud point extraction procedure was presented for the preconcentration of copper(II) ion in various samples. After complexation by 4-(phenyl diazenyl) benzene-1,3-diamine (PDBDM) (chrysoidine), copper(II) ions were quantitatively recovered in Triton X-114 after centrifugation. 0.5 ml of methanol acidified with 1.0 mol L⁻¹ HNO₃ was added to the surfactant-rich phase prior to its analysis by flame atomic absorption spectrometry (FAAS). The influence of analytical parameters including ligand, Triton X-114 and HNO₃ concentrations, bath temperature, heating time, centrifuge rate and time were optimized. The effect of the matrix ions on the recovery of copper(II) ions was investigated. The detection limit (3S.D._b/m, n = 10) of 0.6 ng mL⁻¹ along with preconcentration factor of 30 and enrichment factor of 41.1 with R.S.D. of 1.0% for Cu was achieved. The proposed procedure was applied to the analysis of various environmental and biological samples.     

Trace determination of fluoroquinolone antibacterial agents in urban wastewater by solid-phase extraction and liquid chromatography with fluorescence detection

Fluoroquinolones (FQs) are among the most important antibacterial agents (synthetic antibiotics) used in human and veterinary medicine. An analytical method based on reversed-phase liquid chromatography with fluorescence detection was developed and validated for the simultaneous determination of nine FQs and the quinolone pipemidic acid in urban wastewater. Aqueous samples were extracted using mixed-phase cation-exchange disk cartridges that were subsequently eluted by ammonia solution in methanol. Recoveries were above 80% at an overall precision of better than 10%. Instrumental quantification limits varied between 150 and 450 pg injected. The presented method was successfully applied to quantify FQs in effluents of urban wastewater treatment plants. The two most abundant human-use FQs, ciprofloxacin and norfloxacin, occurred in primary and tertiary waste-water effluents at concentrations between 249 and 405 ng/L and from 45 to 120 ng/L, respectively. The identity of FQs in urban wastewater was confirmed by recording full fluorescence spectra and liquid chromatography directly coupled to tandem mass spectrometry. These results indicate that conventional environmental risk assessment overestimates FQ concentrations in surface waters by 1 to 2 orders of magnitude.     

Using different drift gases to change separation factors (alpha) in ion mobility spectrometry

The use of different drift gases to alter separation factors (alpha) in ion mobility spectrometry has been demonstrated. The mobility of a series of low molecular weight compounds and three small peptides was determined in four different drift gases. The drift gases chosen were helium, argon, nitrogen, and carbon dioxide. These drift gases provide a range of polarizabilities and molecular weights. In all instances, the compounds showed the greatest mobility in helium and the lowest mobility in carbon dioxide; however the percentage change of mobility for each compound was different, effectively changing the alpha value. The alpha value changes were primarily due to differences in drift gas polarizability but were also influenced by the mass of the drift gas. In addition, gas-phase ion radii were calculated in each of the different drift gases. These radii were then plotted against drift gas polarizability producing linear plots with r2 values greater than 0.99. The intercept of these plots provides the gas-phase radius of an ion in a nonpolarizing environment, whereas the slope is indicative of the magnitude of the ion's mobility change related to polarizability. It therefore, should be possible to separate any two compounds that have different slopes with the appropriate drift gas.     

Determination of clenbuterol in bovine liver by combining matrix solid-phase dispersion and molecular imprinted solid-phase extraction followed by liquid chromatography/electrospray ion trap multiple-stage mass spectrometry

Matrix solid-phase dispersion (MSPD) is a new sample pretreatment for solid samples. This technique greatly simplifies sample pretreatment but, nonetheless, the extracts often still require an extra cleanup step that is both laborious and time-consuming. The potential of combining MSPD with molecularly imprinted solid-phase extraction (MISPE) was investigated in this study. Liver samples were ground in a mortar with C18 sorbent and the homogenized mixture packed into an SPE cartridge and placed on top of a MISPE cartridge. Subsequently, clenbuterol was eluted from the MSPD cartridge onto the MISPE cartridge using acetonitrile containing 1% acetic acid. The ability of the molecularly imprinted polymer to selectively adsorb analyte in acetonitrile was exploited for re-extracting clenbuterol directly from this acetonitrile extract via the double cartridge tandem system. The analyte was eluted from the MISPE cartridge using acidified methanol. A clear eluate was obtained, which was subsequently evaporated, redissolved, and analyzed by HPLC electrochemical detection (ECD) or ion trap mass spectrometry (LC/IT-MS). The MISPE cartridge used in this study was imprinted using bromoclenbuterol, a structural analogue of clenbuterol, as the template. These MISPE cartridges showed excellent stability. The complete extraction procedure was rapid, and recoveries exceeded 90% for the target analyte. The method detection limit for the LC/IT-MS procedure was < 0.1 microg/kg. This method, therefore, satisfies the stringent requirements of European Union regulation EEC 2377/90.     

Preconcentration and separation of copper, nickel and zinc in aqueous samples by flame atomic absorption spectrometry after column solid-phase extraction onto MWCNTs impregnated with D2EHPA-TOPO mixture

A solid phase extraction method has been developed for the determination of copper, nickel and zinc ions in natural water samples. This method is based on the adsorption of copper, nickel and zinc on multiwalled carbon nanotubes (MWCNTs) impregnated with di-(2-ethyl hexyl phosphoric acid) (D2EHPA) and tri-n-octyl phosphine oxide (TOPO). The influence of parameters such as pH of the aqueous solution, amount of adsorbent, flow rates of the sample and eluent, matrix effects and D2EHPA-TOPO concentration have been investigated. Desorption studies have been carried out with 2 mol L(-1) HNO(3). The copper, nickel and zinc concentrations were determined by flame atomic absorption spectrometry. The results indicated that the maximum adsorption of copper, nickel and zinc is at pH 5.0 with 500 mg of MWCNTs. The detection limits by three sigma were 50 μg L(-1) for copper, 40 μg L(-1) for nickel and 60 μg L(-1) zinc. The highest enrichment factors were found to be 25. The adsorption capacity of MWCNTs-D2EHPA-TOPO was found to be 4.90 mg g(-1) for copper, 4.78 mg g(-1) for nickel and 4.82 mg g(-1) for zinc. The developed method was applied for the determination of copper, nickel and zinc in electroplating wastewater and real water sample with satisfactory results (R.S.D.'s <10%).     

Accelerated solvent extraction followed by on-line solid-phase extraction coupled to ion trap LC/MS/MS for analysis of benzalkonium chlorides in sediment samples

Benzalkonium chlorides (BACs) were successfully extracted from sediment samples using a new methodology based on accelerated solvent extraction (ASE) followed by an on-line cleanup step. The BACs were detected by liquid chromatography/ion trap mass spectrometry (LC/MS) or tandem mass spectrometry (MS/MS) using an electrospray interface operated in the positive ion mode. This methodology combines the high efficiency of extraction provided by a pressurized fluid and the high sensitivity offered by the ion trap MS/MS. The effects of solvent type and ASE operational variables, such as temperature and pressure, were evaluated. After optimization, a mixture of acetonitrile/water (6:4 or 7:3) was found to be most efficient for extracting BACs from the sediment samples. Extraction recoveries ranged from 95 to 105% for C12 and C14 homologues, respectively. Total method recoveries from fortified sediment samples, using a cleanup step followed byASE, were 85% for C12BAC and 79% for C14BAC. The methodology developed in this work provides detection limits in the subnanogram per gram range. Concentrations of BAC homologues ranged from 22 to 206 microg/kg in sediment samples from different river sites downstream from wastewater treatment plants. The high affinity of BACs for soil suggests that BACs preferentially concentrate in sediment rather than in water.     

Rapid screening of aqueous chemical warfare agent degradation products: ambient pressure ion mobility mass spectrometry

The use of electrospray ionization ambient pressure ion mobility spectrometry with an orthogonal reflector time-of-flight mass spectrometer to analyze chemical warfare (CW) degradation products from aqueous environmental samples has been demonstrated. Certified reference materials of analytical standards for the detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the chemical warfare convention treaty verification were used in this study. A combination of six G/V-type nerve and four S-type vesicant related CW agent degradation products were separated with baseline resolution by this instrumental technique. Analytical figures of merit for each CW degradation product were determined. In some cases, reduced mobility constants (K0) have been reported for the first time. linear response ranges for the selected CW degradation products were found to be generally approximately 2 orders of magnitude, where the overall dynamic response ranges were found to extend to 4 orders of magnitude. Limits of detection for five of the nine chemical products tested were found to be less than 1 ppm. To demonstrate the potential of this instrumental method with complex mixtures, four CW degradation products were separated and detected from a spiked Palouse River water sample in less than 1 min. Finally, a homologous series of n-alkylamines were used as baseline reference standards, producing a mobility/mass trend line to which the CW degradation products could be compared. Comparison of these products in this manner is expected to reduce the number of false positive/negative responses.     

Enhanced detection of nitroaromatic explosive vapors combining solid-phase extraction-air sampling,supercritical fluid extraction,and large-volume injection-GC

A complete method for sampling and analyzing of energetic compounds in the atmosphere is described. The method consists of the hyphenation of several techniques: active air sampling using a solid-phase extraction cartridge to collect the analytes, extraction of the sorbed analytes by toluene/methyl tert-butyl ether modified supercritical fluid extraction (SFE), and analysis of the extract by large-volume injection GC-nitrogen/phosphorus detection. The GC system is equipped with a loop-type injection interface with an early solvent vapor exit, a utilizing concurrent solvent evaporation technique. Chemometric approaches, based on a Plackett-Burman screening design and a central composite design for response surface modeling, were used to determine the optimum SFE conditions. The relative standard deviations of the optimized method were determined to be 4.3 to 7.7%, giving raise to method detection limits ranging from 0.06 to 0.36 ng in the sampling cartridge, equivalent to 6.2-36.4 pg/L in the atmosphere, standard sampling volume 10 L. The analytical method was applied to characterize headspace composition above military grade trinitrotoluene (TNT). Results confirm that 2,4-dinitrotoluene (DNT) and 1,3-dinitrobenzene (DNB) constitute the largest vapor flux, but TNT, 2,6-DNT, and trinitrobenzene TNB were also consistently detected in all the samples.     

Separation and characterization of metallosupramolecular libraries by ion mobility mass spectrometry

The self-assembly of Zn(II) ions and bis(terpyridine) (tpy) ligands carrying 120° or 180° angles between their metal binding sites was utilized to prepare metallosupramolecular libraries with the connectivity. These combinatorial libraries were separated and characterized by ion mobility mass spectrometry (IM MS) and tandem mass spectrometry (MS(2)). The 180°-angle building blocks generate exclusively linear complexes, which were used as standards to determine the architectures of the assemblies resulting from the 120°-angle ligands. The latter ligand geometry promotes the formation of macrocyclic hexamers, but other n-mers with smaller (n = 5) or larger ring sizes (n = 7-9) were identified as minor products, indicating that the angles in the bis(terpyridine) ligand and within the coordinative tpy-Zn(II)-tpy bonds are not as rigid, as previously believed. Macrocyclic and linear isomers were detected in penta- and heptameric assemblies; in the larger octa- and nonameric assemblies, ring-opened conformers with compact and folded geometries were observed in addition to linear extended and cyclic architectures. IM MS(2) experiments provided strong evidence that the macrocycles present in the libraries were already formed in solution, during the self-assembly process, not by dissociation of larger complexes in the gas phase. The IM MS/MS(2) methods provide a means to analyze, based on size and shape (architecture), supramolecular libraries that are not amenable to liquid chromatography, LC-MS, NMR, and/or X-ray techniques.