Improved design for high resolution electrospray ionization ion mobility spectrometry

An improved design for high resolution electrospray ionization ion mobility spectrometry (ESI-IMS) was developed by making some salient modifications to the IMS cell and its performance was investigated. To enhance desolvation of electrospray droplets at high sample flow rates in this new design, volume of the desolvation region was decreased by reducing its diameter and the entrance position of the desolvation gas was shifted to the end of the desolvation region (near the ion gate). In addition, the ESI source (both needle and counter electrode) was positioned outside of the heating oven of the IMS. This modification made it possible to use the instrument at higher temperatures, and preventing needle clogging in the electrospray process. The ion mobility spectra of different chemical compounds were obtained. The resolving power and resolution of the instrument were increased by about 15-30% relative to previous design. In this work, the baseline separation of the two adjacent ion peaks of morphine and those of codeine was achieved for the first time with resolutions of 1.5 and 1.3, respectively. These four ion peaks were well separated from each other using carbon dioxide (CO₂) rather than nitrogen as the drift gas. Finally, the analytical parameters obtained for ethion, metalaxyl, and tributylamine indicated the high performance of the instrument for quantitative analysis.     

Coupling of capillary electrophoresis with electrospray ionization multiplexing ion mobility spectrometry

In this work, ion mobility spectrometry (IMS) function as a detector and another dimension of separation was coupled with CE to achieve two‐dimensional separation. To improve the performance of hyphenated CE‐IMS instrument, electrospray ionization correlation ion mobility spectrometry is evaluated and compared with traditional signal averaging data acquisition method using tetraalkylammonium bromide compounds. The effect of various parameters on the separation including sample introduction, sheath fluid of CE and drift gas, data acquisition method of IMS were investigated. The experimental result shows that the optimal conditions are as follows: hydrodynamic sample injection method, the electrophoresis voltage is 10 kilo volts, 5 mmol/L ammonium acetate buffer solution containing 80% acetonitrile as both the background electrolyte and the electrospray ionization sheath fluid, the ESI liquid flow rate is 4.5 μL/min, the drift voltage is 10.5 kilo volts, the drift gas temperature is 383 K and the drift gas flow rate is 300 mL/min. Under the above conditions, the mixture standards of seven tetraalkylammoniums can be completely separated within 10 min both by CE and IMS. The linear range was 5–250 μg/mL, with LOD of 0.152, 0.204, 0.277, 0.382, 0.466, 0.623 and 0.892 μg/mL, respectively. Compared with traditional capillary electrophoresis detection methods, the developed CE‐ESI‐IMS method not only provide two sets of qualitative parameters including electrophoresis migration time and ion drift time, ion mobility spectrometer can also provide an additional dimension of separation and could apply to the detection ultra‐violet transparent compounds or none fluorescent compounds.     

High resolution electrospray ionization ion mobility spectrometry

Current commercially available ion mobility spectrometers are intended for the analysis of chemicals in the gas phase. Sample introduction methods, such as direct air sampling, a GC injector or a thermal desorber, are commonly an integral part of these instruments. This paper describes an electrospray ionization ion mobility spectrometer system that allows direct introduction samples in solution phase. This allows direct analysis of non-volatile organic and biological samples, and avoids decomposition of thermally liable samples, providing reliable chemical identification. In addition, the new ion mobility spectrometer allows mobility analysis with high resolving power. Commonly used commercial IMS systems provide resolving powers between 10 and 30; this new ion mobility spectrometer has resolving power greater than 60 for routine analysis. A high resolution instrument is necessary for many applications where a complex mixture needs to be separated and quantified. This paper demonstrates the advantages of using a high resolution ion mobility spectrometer and an electrospray ionization source for the analysis of non-volatile pharmaceuticals as well as dissolved explosive in solution phase.     

Separation of benzodiazepines by electrospray ionization ion mobility spectrometry-mass spectrometry

Benzodiazepines are a commonly abused class of drugs; requiring analytical techniques that can separate and detect the drugs in a rapid time period. In this paper, the two-dimensional separation of five benzodiazepines was shown by electrospray ionization (ESI) ion mobility spectrometry (IMS)-mass spectrometry (MS). In this study, both the two dimensions of separation (m/z and mobility) and the high resolution of our IMS instrument enabled confident identification of each of the five benzodiazepines studied. This was a significant improvement over previous IMS studies that could not separate many of the analytes due to low instrumental resolution. The benzodiazepines that contain a hydroxyl group in their molecular structure (lorazepam and oxazepam) were found to form both the protonated molecular ion and dehydration product as predominant ions. Experiments to isolate the parametric reasons for the dehydration ion formation showed that it was not the result of corona discharge processes or the potential applied to the needle. However, the potential difference between the needle and first drift ring did influence both the relative intensity ratios of the two ions and the ion sensitivity.     

Coupling of solid phase microextraction with electrospray ionization ion mobility spectrometry and direct analysis of venlafaxine in human urine and plasma

The capability of electrospray ionization-conventional ion mobility spectrometry (ESI–IMS) for direct analysis of the samples extracted by solid phase microextraction (SPME) was investigated and evaluated for the first time. To that end, an appropriate new desorption chamber was designed and constructed, resulting in the possibility of direct exposure of the SPME fiber to the electrospray solvent flow. Two different elution methods in dynamic and static modes were exhaustively investigated. The results indicated that the interface could help us to have an accurate and sensitive analysis without disturbing the electrospray process, in static elution method. Venlafaxine as a test compound was extracted from human urine and plasma by a convenient headspace SPME method. The positive ion mobility spectrum of the extracted drug was obtained and the analyte responses were calculated. The coupled method of SPME–ESI–IMS was comprehensively validated in terms of sensitivity, dynamic range, and recovery percentage. Finally, various real samples of human urine and plasma were analyzed, all verifying the feasibility and success of the proposed method for the easy routine analysis.     

Selective separation and determination of primidone in pharmaceutical and human serum samples using molecular imprinted polymer-electrospray ionization ion mobility spectrometry (MIP-ESI-IMS)

Application of electrospray ionization ion mobility spectrometry (ESI-IMS) as the detection technique for separation method based on molecular imprinted polymer (MIP) was investigated and evaluated. The method is exhaustively validated, including sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic range of 0.02-2.00 μg mL⁻¹ was obtained for primidone analysis with ESI-IMS. The recovery of drug analyzed was calculated to be above 90% and the relative standard deviation (RSD), was below 3% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient clean-up of the samples using MIP separation before the analysis by ESI-IMS as a detection technique.     

Detection of inorganic ions from water by electrospray ionization-ion mobility spectrometry

The results from this study illustrate the first time electrospray ionization-ion mobility spectrometry (ESI-IMS) has been used to separate inorganic cations in aqueous solutions. Using ESI-IMS nine inorganic cation solutions were analyzed. Counter ions affected both the sensitivity and the identity of the response ions. Aluminum sulfate, lanthanum chloride, strontium chloride, uranyl acetate, uranyl nitrate, and zinc sulfate produced spectra containing a single response ion. Aluminum nitrate and zinc acetate solutions produced multiple ion peaks, which increased the detection limits and the difficulty of identification. Cation detection limits ranged from 0.16 to 13 ng μl⁻¹ depending on the solution studied. The identities of the ion species detected were unconfirmed, but mass spectrometry literature suggested the detection of positively charged cation-solvent or cation-solvent-anion complexes. Finally, cations from strontium and lanthanum chloride solutions were separated with a resolution of 2.2. The results from this study suggest that ESI-IMS has potential as a field technique for the detection of metal cations and their complexes in the environment.     

High‐performance liquid chromatography with electrospray ionization ion mobility spectrometry: Characterization,data management,and applications

The combination of high‐performance liquid chromatography and electrospray ionization ion mobility spectrometry facilitates the two‐dimensional separation of complex mixtures in the retention and drift time plane. The ion mobility spectrometer presented here was optimized for flow rates customarily used in high‐performance liquid chromatography between 100 and 1500 μL/min. The characterization of the system with respect to such parameters as the peak capacity of each time dimension and of the 2D spectrum was carried out based on a separation of a pesticide mixture containing 24 substances. While the total ion current chromatogram is coarsely resolved, exhibiting coelutions for a number of compounds, all substances can be separately detected in the 2D plane due to the orthogonality of the separations in retention and drift dimensions. Another major advantage of the ion mobility detector is the identification of substances based on their characteristic mobilities. Electrospray ionization allows the detection of substances lacking a chromophore. As an example, the separation of a mixture of 18 amino acids is presented. A software built upon the free mass spectrometry package OpenMS was developed for processing the extensive 2D data. The different processing steps are implemented as separate modules which can be arranged in a graphic workflow facilitating automated processing of data.     

Towards metals analysis using corona discharge ionization ion mobility spectrometry

For the first time, the capability of corona discharge ionization ion mobility spectrometry (CD-IMS) in the determination of metal complex was evaluated. The extreme simplicity of dispersive liquid–liquid microextraction (DLLME) coupled to the high sensitivity of CD-IMS measurement could make this combination really useful for simple, rapid, and sensitive determination of metals in different samples. In this regard, mercury, as a model metal, was complexed with diethyldithiocarbamate (DEDTC), and then extracted into the carbon tetrachloride using DLLME. Some parameters affecting the extraction efficiency, including the type and volume of the extraction solvent, the type and volume of the disperser solvent, the concentration of the chelating agent, salt addition and, pH were exhaustively investigated. Under the optimized condition, the enrichment factor was obtained to be 142. The linear range of 0.035–10.0 μg mL⁻¹ with r² = 0.997 and the detection limit of 0.010 μg mL⁻¹ were obtained. The relative standard deviation values were calculated to be lower than 4% and 8% for intra-day and inter-day, respectively. Finally, the developed method was successfully applied for the extraction and determination of mercury in various real samples. The satisfactory results revealed the capability of the proposed method in trace analysis without tedious derivatization or hydride generation.     

Ribonucleotide and ribonucleoside determination by ambient pressure ion mobility spectrometry

Detection limits and reduced mobilities for 12 ribonucleotides and 4 ribonucleosides were measured by ambient pressure electrospray ionization-ion mobility spectrometry (ESI-IMS). With the instrument used in this study it was possible to separate some of these compounds within mixtures. Detection limits reported for ribonucleotides and ribonucleosides ranged from 15 to 300 pmol and the reduced mobilities ranged from 41 to 56 suggesting that ambient pressure ESI-IMS may be used for their rapid and sensitive separation and detection. This report demonstrates that it was possible to use ion mobility spectrometry (IMS) to obtain a spectrum for the separation of nucleotides and nucleosides in less than 1 min. The application holds great promise for nucleotide analysis in the area of separating DNA fragments in genome sequencing and also for forensics DNA typing examinations used for the identification of blood stains in crime scenes and paternity testing.     

Characterization of a distributed plasma ionization source (DPIS) for ion mobility spectrometry and mass spectrometry

A recently developed atmospheric pressure ionization source, a distributed plasma ionization source (DPIS), was characterized and compared to commonly used atmospheric pressure ionization sources with both mass spectrometry (MS) and ion mobility spectrometry (IMS). The source consisted of two electrodes of different sizes separated by a thin dielectric. Application of a high RF voltage across the electrodes generated plasma in air yielding both positive and negative ions. These reactant ions subsequently ionized the analyte vapors. The reactant ions generated were similar to those created in a conventional point-to-plane corona discharge ion source. The positive reactant ions generated by the source were mass identified as being solvated protons of general formula (H₂O)_nH⁺ with (H₂O)₂H⁺ as the most abundant reactant ion. The negative reactant ions produced were mass identified primarily as CO₃⁻, NO₃⁻, NO₂⁻, O₃⁻ and O₂⁻ of various relative intensities. The predominant ion and relative ion ratios varied depending upon source construction and supporting gas flow rates. A few compounds including drugs, explosives and amines were selected to evaluate the new ionization source. The source was operated continuously for 3 months and although surface deterioration was observed visually, the source continued to produce ions at a rate similar that of the initial conditions.     

High-performance ion mobility spectrometry with direct electrospray ionization (ESI-HPIMS) for the detection of additives and contaminants in food

High-performance ion mobility spectrometry (HPIMS) with an electrospray ionization (ESI) source detected a series of food contaminants and additive compounds identified as critical to monitoring the safety of food samples. These compounds included twelve phthalate plasticizers, legal and illegal food and cosmetic dyes, and artificial sweeteners that were all denoted as detection priorities. HPIMS separated and detected the range of compounds with a resolving power better than 60 in both positive and negative ion modes, comparable to the commonly used high-performance liquid chromatography (HPLC) methods, but with most acquisition times under a minute. The reduced mobilities, K₀, have been determined, as have the linear response ranges for ESI-HPIMS, which are 1.5–2 orders of magnitude for concentrations down to sub-ng μL⁻¹ levels. At least one unique mobility peak was seen for two subsets of the phthalates grouped by the country where they were banned. Furthermore, ESI-HPIMS successfully detected low nanogram levels of a phthalate at up to 30 times lower concentration than international detection levels in both a cola matrix and a soy-based bubble tea beverage using only a simplified sample treatment. A newly developed direct ESI source (Directspray) was combined with HPIMS to detect food-grade dyes and industrial dye adulterants, as well as the sweeteners sodium saccharin and sodium cyclamate, with the same good performance as with the phthalates. However, the Directspray method eliminated sources of carryover and decreased the time between sample runs. Limits-of-detection (LOD) for the analyte standards were estimated to be sub-ng μL⁻¹ levels without extensive sample handling or preparation.     

Direct infusion electrospray ionization–ion mobility–mass spectrometry for comparative profiling of fatty acids based on stable isotope labeling

A rapid method for fatty acids (FAs) comparative profiling based on carboxyl-specific stable isotope labeling (SIL) and direct infusion electrospray ionization–ion mobility–mass spectrometry (ESI–IM–MS) is established. The design of the method takes advantage of the three-dimensional characteristics of IM–MS including drift time, m/z and ion intensity, for comparison of d0-/d6-2,4-dimethoxy-6-piperazin-1-yl pyrimidine (DMPP)-labeled FAs. In particular, without chromatographic separation, the method allowed direct FAs profiling in complex samples due to the advantageous priority of DMPP in signal enhancement as well as the extra resolution that IM–MS offered. Additionally, the d0-/d6-DMPP-labeled FAs showed expected features, including very similar drift times, 6 Da mass deviations, specific reporter ions, similar MS responses, and adherence to the drift time rule regarding the influence of carbon chain length and unsaturation on relative drift times. Therefore, the introduction of isotope analogs minimized the matrix effect and variations in quantification and ensured accurate identification of non-targeted FAs by those typical features. Peak intensity ratios between d0-/d6-DMPP-labeled ions were subsequently used in relative quantification for the detected FAs. The established strategy has been applied successfully in the rapid profiling of trace free FAs between normal and cancerous human thyroid tissues. Sixteen free FAs were found with the increased level with a statistically significant difference (p < 0.05) compared to the normal tissue samples. The integrated SIL technique and ESI–IM–MS are expected to serve as an alternative tool for high-throughput analysis of FAs in complex samples.     

Evaluation of false positive responses by mass spectrometry and ion mobility spectrometry for the detection of trace explosives in complex samples

Secondary electrospray ionization-ion mobility-time of flight mass spectrometry (SESI-IM-TOFMS) was used to evaluate common household products and food ingredients for any mass or mobility responses that produced false positives for explosives. These products contained ingredients which shared the same mass and mobility drift time ranges as the analyte ions for common explosives. The results of this study showed that the vast array of compounds in these products can cause either mass or mobility false positive responses. This work also found that two ingredients caused either enhanced or reduced ionization of the target analytes. Another result showed that an IMS can provide real-time separation of ion species that impede accurate mass identifications due to overlapping isotope peak patterns. The final result of this study showed that, when mass and mobility values were used to identify an ion, no false responses were found for the target explosives. The wider implication of these results is that the possibility exists for even greater occurrences of false responses from complex mixtures found in common products. Neither IMS nor MS alone can provide 100% assurance from false responses. IMS, due to its low cost, ease of operation, rugged reliability, high sensitivity and tunable selectivity, will remain the field method of choice for the near future but, when combined with MS, can also reduce the false positive rate for explosive analyses.     

A review of recent, unconventional applications of ion mobility spectrometry (IMS)

The applications of ion mobility spectrometry (IMS) have grown exponentially beyond its uses for explosive, illicit drug and chemical warfare agent monitoring in recent years. Instrumental developments including new drift tube materials and ionization sources have enabled the manufacturing of more sophisticated and affordable IMS equipment for the advantageous analysis of samples with no pretreatment. The most recent applications of IMS include quality control and cleaning validation procedures in the pharmaceutical industry; determinations of contaminants in food samples; clinical analyses of biological fluids; environmental analyses of contaminants in gaseous, liquid and solid samples; and (bio)process quality control monitoring. Coupling IMS with MSⁿ has enabled the analysis of very complex samples and the extraction of knowledge unavailable from isolated MS measurements, especially in the polymer and petroleomic industries.     

Analysis of biogenic amines using corona discharge ion mobility spectrometry

A new method based on corona discharge ion mobility spectrometry (CD-IMS) was developed for the analysis of biogenic amines including spermidine, spermine, putrescine, and cadaverine. The ion mobility spectra of the compounds were obtained with and without n-Nonylamine used as the reagent gas. The high proton affinity of n-Nonylamine prevented ion formation from compounds with a proton affinity lower than that of n-Nonylamine and, therefore, enhanced its selectivity. It was also realized that the ion mobility spectrum of n-Nonylamine varied with its concentration. A sample injection port of a gas chromatograph was modified and used as the sample introduction system into the CD-IMS. The detection limits, dynamic ranges, and analytical parameters of the compounds with and without using the reagent gas were obtained. The detection limits and dynamic ranges of the compounds were about 2 ng and 2 orders of magnitude, respectively. The wide dynamic range of CD-IMS originates from the high current of the corona discharge. The results revealed the high capability of the CD-IMS for the analysis of biogenic amines.     

Comprehensive ultra-high pressure capillary liquid chromatography/ion mobility spectrometry

Summary An ultra-high pressure liquid chromatograph was interfaced to a moderately high-resolution nanoelectrospray ionization ion mobility spectrometer operating at ambient temperature and pressure to achieve fast multidimensional separations. The potential of using ion mobility spectrometry as the second dimension in a comprehensive arrangement with liquid chromatography to offer improved qualitative information for compounds under specific operating conditions, is discussed. Separation and detection of selected benzodiazepines and triazine herbicides are demonstrated. Composite peak capacities of 39 and 33 for benzodiazepine and triazine herbicide mixtures, respectively, were achieved in less than 75 s using a 16.5 cm×50 μm internal diameter fused silica capillary liquid chromatographic column packed with 1.5 μm diameter ODS-bonded silica particles.     

Identity confirmation of drugs and explosives in ion mobility spectrometry using a secondary drift gas

This work demonstrated the potential of using a secondary drift gas of differing polarizability from the primary drift gas for confirmation of a positive response for drugs or explosives by ion mobility spectrometry (IMS). The gas phase mobilities of response ions for selected drugs and explosives were measured in four drift gases. The drift gases chosen for this study were air, nitrogen, carbon dioxide and nitrous oxide providing a range of polarizability and molecular weights. Four other drift gases (helium, neon, argon and sulfur hexafluoride) were also investigated but design limitations of the commercial instrument prevented their use for this application. When ion mobility was plotted against drift gas polarizability, the resulting slopes were often unique for individual ions, indicating that selectivity factors between any two analytes varied with the choice of drift gas. In some cases, drugs like THC and heroin, which are unresolved in air or nitrogen, were well resolved in carbon dioxide or nitrous oxide.     

Fingerprinting bacterial strains using ion mobility spectrometry

Ion mobility spectrometry (IMS) is currently in widespread use for the detection and identification of narcotic and explosive compounds without prior sample clean-up or concentration steps. IMS analysis is rapid, less than a minute, and sensitive, with detection limits in the nanogram to picogram range, depending on the target analyte. Our studies indicate that this technique has potential for detection of specific components of bacterial cells and for identification and differentiation of bacterial strains and species within a minute, and with no specialized test kits or reagents required. When microgram quantities of whole bacterial cells are thermally desorbed, complex positive or negative ion patterns (plasmagrams) are obtained. These plasmagrams differ reproducibly for different strains and species and for different conditions of growth, and can be used for the classification and differentiation of specific strains and species of bacteria, including pathogens. Methods for improved ion peak detection, most notably sequential sample desorption at stepped increases in temperature (programmed temperature ramping), are described.     

The coupling of solid-phase microextraction/surface enhanced laser desorption/ionization to ion mobility spectrometry for drug analysis

The construction of a new solid-phase microextraction/surfaced enhanced laser desorption/ionization-ion mobility spectrometry (SPME/SELDI-IMS) device is reported here. A polypyrrole (PPY) coated SPME/SELDI fiber was employed as the extraction phase and SELDI surface to introduce analytes into the IMS. Analytes were directly ionized from the PPY coated fiber tip by a Nd:YAG laser without the addition of a matrix. Optimal experimental parameters, such as extraction conditions and laser parameters, were investigated. The use of a SPME/SELDI fiber simplified the sampling and sample preparation for IMS. Verapamil could be directly extracted from urine sample and analyzed by IMS without any further sample cleanup. This technique could be used for the analysis of drugs and other non-volatile compounds.