Analysis of lipids with desorption atmospheric pressure photoionization‐mass spectrometry (DAPPI‐MS) and desorption electrospray ionization‐mass spectrometry (DESI‐MS)

In this article, the effect of spray solvent on the analysis of selected lipids including fatty acids, fat‐soluble vitamins, triacylglycerols, steroids, phospholipids, and sphingolipids has been studied by two different ambient mass spectrometry (MS) methods, desorption electrospray ionization‐MS (DESI‐MS) and desorption atmospheric pressure photoionization‐MS (DAPPI‐MS). The ionization of the lipids with DESI and DAPPI was strongly dependent on the spray solvent. In most cases, the lipids were detected as protonated or deprotonated molecules; however, other ions were also formed, such as adduct ions (in DESI), [M‐H]⁺ ions (in DESI and DAPPI), radical ions (in DAPPI), and abundant oxidation products (in DESI and DAPPI). DAPPI provided efficient desorption and ionization for neutral and less polar as well as for ionic lipids but caused extensive fragmentation for larger and more labile compounds because of a thermal desorption process. DESI was more suitable for the analysis of the large and labile lipids, but the ionization efficiency for less polar lipids was poor. Both methods were successfully applied to the direct analysis of lipids from pharmaceutical and food products. Although DESI and DAPPI provide efficient analysis of lipids, the multiple and largely unpredictable ionization reactions may set challenges for routine lipid analysis with these methods. Copyright © 2012 John Wiley & Sons, Ltd.     

Desorption electrospray ionization ‐ orbitrap mass spectrometry of synthetic polymers and copolymers

Desorption ElectroSpray Ionization (DESI) ‐ Orbitrap Mass Spectrometry (MS) was evaluated as a new tool for the characterization of various industrial synthetic polymers (poly(ethylene glycol), poly(propylene glycol), poly(methylmethacrylate), poly(dimethylsiloxane)) and copolymers, with masses ranging from 500 g.mol⁻¹ up to more than 20 000 g.mol⁻¹. Satisfying results in terms of signal stability and sensitivity were obtained from hydrophobic surfaces (HTC Prosolia) with a mixture water/methanol (10/90) as spray solvent in the presence of sodium salt. Taking into account the formation of multiplied charged species by DESI‐MS, a strategy based on the use of a deconvolution software followed by the automatic assignment of the ions was described allowing the rapid determination of M_n, M_w and PDI values. DESI‐Orbitrap MS results were compared to those obtained from matrix‐assisted laser desorption/ionization‐ time‐of‐flight MS and gel permeation chromatography. An application of DESI‐Orbitrap MS for the detection and identification of polymers directly from cosmetics was described. Copyright © 2012 John Wiley & Sons, Ltd.     

Detection of the Short‐Lived Radical Cation Intermediate in the Electrooxidation of N,N‐Dimethylaniline by Mass Spectrometry

The N,N‐dimethylaniline (DMA) radical cation DMA^.+, a long‐sought transient intermediate, was detected by mass spectrometry (MS) during the electrochemical oxidation of DMA. This was accomplished by coupling desorption electrospray ionization (DESI) MS with a waterwheel working electrode setup to sample the surface of the working electrode during electrochemical analysis. This study clearly shows that DESI‐based electrochemical MS is capable of capturing electrochemically generated intermediates with half‐lives on the order of microseconds, which is 4–5 orders of magnitude faster than previously reported electrochemical mass spectrometry techniques.     

A dopant for improved sensitivity in easy ambient sonic‐spray ionization mass spectrometry

Recently, 3‐nitrobenzonitrile (3‐NBN) has been used to improve sensitivity of sonic‐spray ionization mass spectrometry. Easy ambient sonic‐spray ionization (EASI) is one of the simplest, gentlest and most used spray‐based desorption/ionization ambient techniques, but limited sensitivity has been commonly taken as its major drawback. Herein we investigate the use of 3‐NBN as a dopant in EASI‐MS for improved sensitivity. Using a few typical EASI samples as test cases, the presence of 10 ppm (µg ml^?1) of 3‐NBN in the spray solvent showed two to fourfold gains in EASI‐MS sensitivity as measured both by total ion current and S/N ratios, accompanied with significant reductions in chemical noise. Sensitivity for DESI using 3‐NBN as a dopant also improved and dopant DESI versus dopant EASI sensitivities were compared. The use of solvent dopants seems therefore to be a promising strategy to improve sensitivity for spray‐based ambient MS techniques. Copyright © 2015 John Wiley & Sons, Ltd.     

Protein analysis by desorption electrospray ionization mass spectrometry and related methods

Desorption electrospray ionization mass spectrometry (DESI‐MS) requires little to no sample preparation and has been successfully applied to the study of biologically significant macromolecules such as proteins. However, DESI‐MS and other ambient methods that use spray desorption to process samples during ionization appear limited to smaller proteins with molecular masses of 25 kDa or less, and a decreasing instrumental response with increasing protein size has often been reported. It has been proposed that this limit results from the inability of some proteins to easily desorb from the surface during DESI sampling. The present study investigates the apparent mass dependence of the instrumental response observed during the DESI‐MS analysis of proteins using spray desorption collection and reflective electrospray ionization. Proteins, as large as 66 kDa, are shown to be quantitatively removed from surfaces by using spray desorption collection. However, incomplete dissolution and the formation of protein–protein and protein–contaminant clusters appear to be responsible for the mass‐dependent loss in sensitivity for protein analysis. Alternative ambient mass spectrometry approaches that address some of the problems encountered by spray desorption techniques for protein analysis are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.     

Direct analysis of pharmaceutical formulations from non‐bonded reversed‐phase thin‐layer chromatography plates by desorption electrospray ionisation ion mobility mass spectrometry

The direct analysis of pharmaceutical formulations and active ingredients from non‐bonded reversed‐phase thin layer chromatography (RP‐TLC) plates by desorption electrospray ionisation (DESI) combined with ion mobility mass spectrometry (IM‐MS) is reported. The analysis of formulations containing analgesic (paracetamol), decongestant (ephedrine), opiate (codeine) and stimulant (caffeine) active pharmaceutical ingredients is described, with and without chromatographic development to separate the active ingredients from the excipient formulation. Selectivity was enhanced by combining ion mobility and mass spectrometry to characterise the desorbed gas‐phase analyte ions on the basis of mass‐to‐charge ratio (m/z) and gas‐phase ion mobility (drift time). The solvent composition of the DESI spray using a step gradient was varied to optimise the desorption of active pharmaceutical ingredients from the RP‐TLC plates. The combined RP‐TLC/DESI‐IM‐MS approach has potential as a rapid and selective technique for pharmaceutical analysis by orthogonal gas‐phase electrophoretic and mass‐to‐charge separation. Copyright © 2009 John Wiley & Sons, Ltd.     

Direct analysis of Salvia divinorum leaves for salvinorin A by thin layer chromatography and desorption electrospray ionization multi‐stage tandem mass spectrometry

Salvia divinorum is widely cultivated in the US, Mexico, Central and South America and Europe and is consumed for its ability to produce hallucinogenic effects similar to those of other scheduled hallucinogenic drugs, such as LSD. Salvinorin A (SA), a kappa opiod receptor agonist and psychoactive constituent, is found primarily in the leaves and to a lesser extent in the stems of the plant. Herein, the analysis of intact S. divinorum leaves for SA and of acetone extracts separated using thin layer chromatography (TLC) is demonstrated using desorption electrospray ionization (DESI) mass spectrometry. The detection of SA using DESI in the positive ion mode is characterized by several ions associated with the compound – [M+H]⁺, [M+NH₄]⁺, [M+Na]⁺, [2M+NH₄]⁺, and [2M+Na]⁺. Confirmation of the identity of these ions is provided through exact mass measurements using a time‐of‐flight (ToF) mass spectrometer. The presence of SA in the leaves was confirmed by multi‐stage tandem mass spectrometry (MSⁿ) of the [M+H]⁺ ion using a linear ion trap mass spectrometer. Direct analysis of the leaves revealed several species of salvinorin in addition to SA as confirmed by MSⁿ, including salvinorin B, C, D/E, and divinatorin B. Further, the results from DESI imaging of a TLC separation of a commercial leaf extract and an acetone extract of S. divinorum leaves were in concordance with the TLC/DESI‐MS results of an authentic salvinorin A standard. The present study provides an example of both the direct analysis of intact plant materials for screening illicit substances and the coupling of TLC and DESI‐MS as a simple method for the examination of natural products. Copyright © 2010 John Wiley & Sons, Ltd.     

Desorption electrospray ionization mass spectrometric analysis of organophosphorus chemical warfare agents using ion mobility and tandem mass spectrometry

Desorption electrospray ionization mass spectrometry (DESI‐MS) has been applied to the direct analysis of sample media for target chemicals, including chemical warfare agents (CWA), without the need for additional sample handling. During the present study, solid‐phase microextraction (SPME) fibers were used to sample the headspace above five organophosphorus CWA, O‐isopropyl methylphosphonofluoridate (sarin, GB), O‐pinacolyl methylphosphonofluoridate (soman, GD), O‐ethyl N,N‐dimethyl phosphoramidocyanidate (tabun, GA), O‐cyclohexyl methylphosphonofluoridate (cyclohexyl sarin, GF) and O‐ethyl S‐2‐diisopropylaminoethyl methyl phosphonothiolate (VX) spiked into glass headspace sampling vials. Following sampling, the SPME fibers were introduced directly into a modified ESI source, enabling rapid and safe DESI of the toxic compounds. A SYNAPT HDMS? instrument was used to acquire time‐aligned parallel (TAP) fragmentation data, which provided both ion mobility and MSⁿ (n = 2 or 3) data useful for the confirmation of CWA. Unique ion mobility profiles were acquired for each compound and characteristic product ions of the ion mobility separated ions were produced in the Triwave? transfer collision region. Up to six full scanning MSⁿ spectra, containing the [M + H]⁺ ion and up to seven diagnostic product ions, were acquired for each CWA during SPME fiber analysis. A rapid screening approach, based on the developed methodology, was applied to several typical forensic media, including Dacron sampling swabs spiked with 5 µg of CWA. Background interference was minimal and the spiked CWA were readily identified within one minute on the basis of the acquired ion mobility and mass spectrometric data. Copyright © 2010 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.     

Spray desorption collection: an alternative to swabbing for pharmaceutical cleaning validation

Spray Desorption Collection (SDC) allows for much larger areas of surfaces to be sampled compared to traditional swabbing techniques, providing a valuable pre-concentration advantage. Closely related to desorption electrospray ionization (DESI), analytes from the sample surface are collected onto a selected collection surface, which in a second step can be analyzed directly. Here we demonstrate the application of SDC as a large surface area sampling tool coupled with paper spray MS (PS-MS) and demonstrate its capabilities for cleaning validation of pharmaceutical equipment for both acidic and basic active ingredients from an aluminium surface.     

Improved desorption electrospray ionization mass spectrometry performance using edge sampling and a rotational sample stage

The position of the surface to be analyzed relative to the sampling orifice or capillary into the mass spectrometer has been known to dramatically affect the observed signal levels in desorption electrospray ionization mass spectrometry (DESI‐MS). In analyses of sample spots on planar surfaces, DESI‐MS signal intensities as much as five times greater were routinely observed when the bottom of the sampling capillary was appropriately positioned beneath the surface plane (‘edge sampling’) compared with when the capillary just touched the surface. To take advantage of the optimum ‘edge sampling’ geometry and to maximize the number of samples that could be analyzed in this configuration, a rotational sample stage was integrated into a typical DESI‐MS setup. The rapid quantitative determination of caffeine in two diet sport drinks spiked with an isotopically labeled internal standard demonstrated the utility of this approach. Published in 2008 by John Wiley & Sons, Ltd.     

Desorption electrospray ionisation mass spectrometric analysis of chemical warfare agents from solid‐phase microextraction fibers

Desorption electrospray ionisation mass spectrometry (DESI‐MS) was recently reported for the direct analysis of sample media without the need for additional sample handling. During the present study, direct analysis of solid‐phase microextraction (SPME) fibers by DESI‐MS/MS was evaluated with indoor office media that might be collected during a forensic investigation, including wall surfaces, office fabrics, paper products and Dacron swabs used for liquid sampling. Media spiked at the µg/g level with purified chemical warfare agents and a complex munitions grade sample of tabun, to simulate the quality of chemical warfare agent that might be used for terrorist purposes, were successfully analysed by DESI‐MS/MS. Sulfur mustard, a compound that has not been successfully analysed by electrospray mass spectrometry in the past, was also sampled using a SPME fiber and analysed for the first time by DESI‐MS/MS. Finally, the overall analytical approach involving SPME headspace sampling and DESI‐MS analysis was evaluated during a scenario‐based training live agent exercise. A sarin sample collected by the military was analysed and confirmed by DESI‐MS in a mobile laboratory under realistic field conditions. Copyright © 2007 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.     

Time‐of‐flight mass spectrometry for time‐resolved measurements: Some developments and applications

In this paper, the time resolution for kinetic studies of reactions with mass spectrometric detection is characterized in detail, and it is shown how this allows faster kinetic processes to be determined. The time‐resolved technique used pulsed laser photolysis to initiate reaction and a time‐of‐flight mass spectrometer (TOFMS) to monitor progress, where the reactant gas was sampled by a sampling orifice and photoionized using pulsed, laser vacuum ultraviolet light before being analyzed by the TOFMS. Characterization of this setup has been carried out to identify the parameters that affect the time for “sampling,” which limits the fastest reactions that can be measured. A simple mathematical equation has been developed to correct for “sampling” delays (k_sampling～25, 000 s^?1), which extends the range of rate coefficients to be measured in a kinetic mass spectrometry reactor to k′ < 7000 s^?1. This method could be applied to any other kinetic mass spectrometry system where k_sampling can be measured; an important advantage since it allows the study of reactions over a wider range of conditions (e.g., larger concentrations of reagents/products can be used to minimize the contribution from wall losses). The system can produce reliable kinetic data whether monitoring reactant decay or product growth even when the reaction and sampling processes are occurring on a similar timescale (k′ < 7000 s^?1). Reproducible and reliable kinetic data have been obtained for the following reactions: SO + NO₂ → products (R1), ClSO + NO₂ → products (R2), where SO and ClSO were monitored under pseudo‐first‐order conditions, and HCO + O₂ → CO + HO₂ (R3), where CO was monitored by a [1+1] resonance enhanced ionization multiphoton ionization (REMPI) scheme with HCO reacting under pseudo–first‐order conditions. The limitations and potential developments of this setup are described. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 44: 532–545, 2012     

Reactive desorption electrospray ionization for rapid screening of guests for supramolecular inclusion complexes

Reactive desorption electrospray ionization (DESI), an ambient technique, has been explored as a tool for the development of a fast screening approach for supramolecular complexes capitalizing on the specificity of mass spectrometric detection. A library of twelve potential guests for inclusion by a β‐cyclodextrin host was initially screened via DESI using a spray solution incorporating the host directed toward an array of deposited guests. The steroid nortestosterone was used to verify the applicability of reactive DESI for complexation experiments with β‐cyclodextrin. Results from the DESI experiment and results from an analogous electrospray ionization (ESI) mass spectral screen were compared with solution‐phase data obtained by nuclear magnetic resonance (NMR) spectroscopy. The complexes detected using DESI were identical to those determined using NMR, validating the applicability of the technique to supramolecular applications, but the ESI data exhibited significant disparities, predominantly due to the interference of nonspecific artifacts. Copyright © 2008 John Wiley & Sons, Ltd.     

Desorption electrospray ionization with a portable mass spectrometer: in situ analysis of ambient surfaces

Desorption electrospray ionization (DESI) is implemented on a portable mass spectrometer and used to demonstrate in situ detection of active ingredients in pharmaceutical preparations, alkaloids in plant tissues, explosives, chemical warfare agent simulants and agricultural chemicals from a variety of surfaces; air monitoring applications using DESI are also introduced.     

Evaluation of electron capture detection in reversed‐phase HPLC for pharmaceutical analysis

The coupling of RP‐LC to electron capture detection (ECDNi⁶³) is described. To reduce the amount of mobile phase entering into the detector, interfacing was performed via a Scott‐type spray chamber. The performance of RP‐LC/ECDNi⁶³ was evaluated for pharmaceutical analysis and the results show that the system is able to work in a routine environment using columns with 2 mm id and common amounts of the organic modifiers methanol or ACN in the mobile phase. Because of the high sensitivity and selectivity toward electrophilic compounds, the use of this detector opens possibilities for the analysis of impurities down to the 0.05% level of active pharmaceutical ingredients (API).     

Large‐scale isolation of high‐purity anthocyanin monomers from mulberry fruits by combined chromatographic techniques

Anthocyanins have attracted attention over the past several decades because of their beneficial health effects. In this research, a strategy combining column chromatography and high‐speed countercurrent chromatography was developed for the separation of high‐purity anthocyanin monomers from mulberry fruits. After purification using Amberlite XAD‐7HP column with 80% ethanol (0.1% HCl), a fraction of anthocyanins mixtures with a purity of 68.6% was obtained. High‐speed countercurrent chromatography with a biphasic solvent system of n‐butanol/methyl tert‐butyl ether/acetonitrile/water/trifluoroacetic acid (30:10:10:50:0.05, v/v) was used to separate the anthocyanin monomers. Three monomers of delphinidin‐3‐O‐ rutinoside, cyanidin‐3‐O‐ rutinoside, and cyanidin‐3‐O‐ glucoside were obtained, and identified by ¹H and ¹³C NMR spectroscopy and high‐performance liquid chromatography with electrospray ionization‐mass spectrometry. The method developed in this work can be used to conduct large‐scale separations of anthocyanin monomers from mulberry fruits and other plants.     

Use of whole‐body cryosectioning and desorption electrospray ionization mass spectrometry imaging to visualize alkaloid distribution in poison frogs

Ambient mass spectrometry is useful for analyzing compounds that would be affected by other chemical procedures. Poison frogs are known to sequester alkaloids from their diet, but the sequestration pathway is unknown. Here, we describe methods for whole‐body cryosectioning of frogs and use desorption electrospray ionization mass spectrometry imaging (DESI‐MSI) to map the orally administered alkaloid histrionicotoxin 235A in a whole‐body section of the poison frog Dendrobates tinctorius. Our results show that whole‐body cryosectioning coupled with histochemical staining and DESI‐MSI is an effective technique to visualize alkaloid distribution and help elucidate the mechanisms involved in alkaloid sequestration in poison frogs.     

Direct detection of chlorpropham on potato skin using desorption electrospray ionization

Most pesticides, herbicides and other plant treatment agents are applied to the crop surface. Direct mass spectrometric methods, such as desorption electrospray ionization (DESI), offer new ways to analyze plant samples directly and rapidly. A strategy for the development and optimization of a DESI method for the direct determination of chemicals on complex surfaces is described. Chlorpropham (CP) was applied to potato surfaces as an example for a crop protection agent and analyzed using a self‐made DESI source. Aspects such as instrument selectivity, sensitivity and reproducibility were investigated. The MS⁴ fragmentation pattern of CP was analyzed to achieve the necessary detection selectivity, and is discussed in detail. Similar fragmentation was found in the ESI and DESI mass spectra, indicating that the mechanisms of ESI and DESI are closely related. A DESI method for semi‐quantification of CP on potatoes was developed. Detection limits of 6.5 µg/kg were found using MS/MS. The reproducibility, in the range of 12% (signal variation), appears to be sufficient for semi‐quantitative measurements. Copyright © 2013 John Wiley & Sons, Ltd.     

Analysis of impurities in pharmaceuticals by LC‐MS with cold electron ionization

Pharmaceuticals require careful and precise determination of their impurities that might harm the user upon consumption. Although today, the most common technique for impurities identification is liquid chromatography‐mass spectrometry (LC‐MS/MS), it has several downsides due to the nature of the ionization method. Also, the analyses in many cases are targeted thus despite being present, some of the compounds will not be revealed. In this paper, we propose and show a new method for untargeted analysis and identification of impurities in active pharmaceutical ingredients (APIs). The instrument used for these analyses is a novel electron ionization (EI) LC‐MS with supersonic molecular beams (SMB). The EI‐LC‐MS‐SMB was implemented for analyses of several drug samples spiked with an impurity. The instrument provides EI mass spectra with enhanced molecular ions, named Cold EI, which increases the identification probabilities when the compound is identified with the aid of an EI library like National Institute of Standards and Technology (NIST). We analyzed ibuprofen and its impurities, and both the API and the expected impurity were identified with names and structures by the NIST library. Moreover, other unexpected impurities were found and identified proving the ability of the EI‐LC‐MS‐SMB system for truly untargeted analysis. The results show a broad dynamic range of four orders of magnitude at the same run with a signal‐to‐noise ratio of over 10 000 for the API and almost uniform response.     

Synthesis and characterization of fully aliphatic polyimides from an aliphatic dianhydride with piperazine spacer for enhanced solubility,transparency, and low dielectric constant

A new series of fully aliphatic polyimide (API) based on a novel aliphatic dianhydride monomer‐2,2′‐(1,4‐piperazinediyl)‐disuccinic anhydride (PDA), in which two units of succinic anhydride have been connected by an aliphatic heterocyclic piperazine spacer that possesses aminomethylene (‐NCH₂) moiety in the aliphatic/alicylic backbone capable of inducing charge transfer (CT) interactions in the polyimide network, was successfully synthesized. The APIs were soluble in common polar organic solvents. The polyimide films of PDA with alicyclic diamines were almost colorless. T₁₀ (temperature of 10% weight loss) of APIs were ranged from 299–418 °C and T_g of API3‐API6 were in the temperature range of 170 to 237 °C. The light‐colored polyimide films of API3‐API6 possessed good mechanical properties with tensile strength of 54–72 Mpa, tensile modulus of 1.6–2.3 Gpa and elongation at break of 4–9%. The polyimide films of API3‐API6 were highly flexible and free‐standing which is quite rare in fully APIs. The dielectric constant of one of the synthesized API (API4) was as low as 2.14. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2316–2328