High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) and Differential Mobility Spectrometry (DMS) harness differences in ion mobility in low and high electric fields to achieve a gas-phase separation of ions at atmospheric pressure. This separation is orthogonal to either chromatographic or mass spectrometric separation, thereby increasing the selectivity and specificity of analysis. The orthogonality of separation, which in some cases may obviate chromatographic separation, can be used to differentiate isomers, to reduce background, to resolve isobaric species, and to improve signal-to-noise ratios by selective ion transmission. This review will focus on the applications of these techniques to the separation of various classes of analytes, including chemical weapons, explosives, biologically active molecules, pharmaceuticals and pollutants. These papers cover the period up to January 2007.

The effect of metabolite interference during liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis of an amine drug was investigated using FAIMS (high-Field Asymmetric waveform Ion Mobility Spectrometry). The selected reaction monitoring (SRM) transition used for the drug exhibited an interference due to in-source conversion of the N-oxide metabolite to generate an ion isobaric with the drug. The on-line FAIMS device removed the metabolite interference before entrance to the mass spectrometer. FAIMS was used to demonstrate the relative accuracy and precision of drug analysis even in the presence of a co-eluting metabolite that may undergo insource conversion. Copyright # 2005 John Wiley & Sons, Ltd.Liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) is a standard technique for bioanalysis in the pharmaceutical industry.1-4 One of the main reasons for the success of LC/MS/MS is the very high level of selectivity that can be routinely achieved. This selectivity is due to the distinct nature of the separation mechanisms of each individual technique involved in LC/MS/MS bioanalysis. The condensed-phase LC separation provides selectivity based on the physicochemical properties of the analyte in relation to mobile and stationary phases. In contrast, the gas-phase MS/MS separation offers selectivity based on mass-to-charge (m/z) ratio differences as well as chemical fragmentation. When these two orthogonal techniques are used together, the combined selectivity allows for very low limits of quantitation with accurate determinations of drug levels in complex matrices. In addition to enhanced selectivity, the introduction of LC/ MS/MS has demonstrated the potential for increases in sample throughput. In the race to produce the next blockbuster drug, pharmaceutical companies and contract research organizations analyze many samples in increasingly shorter periods of time. Common bioanalytical laboratory practices to reduce this time-to-market include minimizing the effort put into sample preparation, reducing or eliminating chromatographic analyses, and using elaborate MS n techniques.5-9 However, the race for higher throughput must be balanced with the requirement of maintaining sufficient selectivity. One potential source for loss of selectivity in LC/ MS/MS bioanalysis is the interference of a metabolite that can undergo in-source conversion. The interference problem arises from the fact that the metabolite can produce a molecular ion identical to the molecular ion of the drug. This conversion may be due to thermal decomposition during sample ionization, which has been observed during atmospheric pressure chemical ionization (APCI). 10 In contrast, the conversion may be the result of the cone voltage causing in-source collisionally activated dissociation (in-source CAD), as ions enter the moderate-pressure region of the vacuum chamber prior to mass analysis. The presence of a prodrug, due to incomplete in vivo conversion into the intended drug, could also cause a similar interference in t...

Flow injection high field asymmetric waveform ion mobility spectrometry (FAIMS)-mass spectrometry (MS) methodology was developed for the detection and identification of chemical warfare (CW) agents in spiked food products. The CW agents, soman (GD), sarin (GB), tabun (GA), cyclohexyl sarin (GF), and four hydrolysis products, ethylphosphonic acid (EPA), methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (Pin MPA), and isopropyl methylphosphonic acid (IMPA) were separated and detected by positive ion and negative ion atmospheric pressure ionization-FAIMS-MS. Under optimized conditions, the compensation voltages were 7.2 V for GD, 8.0 V for GA, 7.2 V for GF, 7.6 V for GB, 18.2 V for EPA, 25.9 V for MPA, -1.9 V for PinMPA, and +6.8 V for IMPA. Sample preparation was kept to a minimum, resulting in analysis times of 3 min or less per sample. The developed methodology was evaluated by spiking bottled water, canola oil, cornmeal, and honey samples at low microgram per gram (or microg/mL) levels with the CW agents or CW agent hydrolysis products. The detection limits observed for the CW agents in the spiked food samples ranged from 3 to 15 ng/mL in bottled water, 1-33 ng/mL in canola oil, 1-34 ng/g in cornmeal, and 13-18 ng/g in honey. Detection limits were much higher for the CW agent hydrolysis products, with only MPA being detected in spiked honey samples.

Underlying the risk management of pesticides to protect human health and to facilitate trade among nations are sound scientific data on the levels of compliance with standards set by governments and internationally from monitoring of the levels of pesticides in foods. Although glyphosate is among the universally used pesticides in the world, monitoring has been hampered by the analytical difficulties in dealing with this highly polar compound. Starting in 2015, using liquid chromatography/tandem mass spectrometry (LC-MS/MS) that permits accurate and reproducible determination of glyphosate, the prevalence, concentrations, and compliance rates were determined. In this work, the glyphosate residues contents of 7955 samples of fresh fruits and vegetables, milled grain products, pulse products, and finished foods collected from April 2015 to March 2017 in the Canadian retail market are reported. A total of 3366 samples (42.3%) contained detectable glyphosate residues. The compliance rate with Canadian regulations was 99.4%. There were 46 noncompliant samples. Health Canada determined that there was no long-term health risk to Canadian consumers from exposure to the levels of glyphosate found in the samples of a variety of foods surveyed. The high level of compliance (99.4% of samples with the Canadian regulatory limits) and the lack of a health risk for noncompliant samples indicate that, with respect to glyphosates, the food available for sale in Canada is safe.

The separation and ion focusing properties of High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) depend on desolvated ions entering the device, leading to a compound-specific, reproducible compensation voltage (CV) for each ion. This study shows that the conditions identified for stable spray and satisfactory ion desolvation in normal electrospray ionization mass spectrometry (ESI-MS) operation might significantly differ from those required for FAIMS-MS. In a typical setup with high-flow electrospray conditions, ions could be incompletely desolvated, resulting in the formation of unidentified clusters with differing behavior in a FAIMS environment. This causes compound-specific shifts of as much as 10 V in CV values when the mobile phase composition and/or flow rate are varied. The shifts diminish and finally disappear when the flow rate of methanol, used as mobile phase, is reduced to 40 microL/min and that of acetonitrile to 20 microL/min. The reproducibility of the observed CV was determined by scanning the CV while infusing a five-component mixture into a 400 microL/min flow of methanol or 50:50 acetonitrile/water. The relative standard deviation (RSD) for these multiple scans ranged from 0.7% to 6%. Therefore, under a constant set of experimental parameters, the CV does not shift appreciably. These observations have an impact on method development strategies. High flow rates can be used with the FAIMS device, since the CV values are reproducible, but it is likely that clusters are forming. Therefore, CV scans should be performed under conditions which mimic the chromatographic elution or flow injection analysis conditions, including matrix composition, to minimize errors in CV determination. An alternative approach is to determine the liquid flow rate at which the CV becomes compound-specific and to split the mobile phase stream accordingly. These experimental results may be specific to the setup used for this study and may not be directly applicable to other instrument FAIMS devices.