Tiina J. Kauppila

Effect of eluent on the ionization process in liquid chromatography-mass spectrometry.

The most widely used ionization techniques in liquid chromatography-mass spectrometry (LC-MS) are electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). All three provide user friendly coupling of LC to MS. Achieving optimal LC-MS conditions is not always easy, however, owing to the complexity of ionization processes and the many parameters affecting mass spectrometric sensitivity and chromatographic performance. The selection of eluent composition requires particular attention since a solvent that is optimal for analyte ionization often does not provide acceptable retention and resolution in LC. Compromises must then be made between ionization and chromatographic separation efficiencies. The review presents an overview of studies concerning the effect of eluent composition on the ionization efficiency of ESI, APCI and APPI in LC-MS. Solvent characteristics are discussed in the light of ionization theories, and selected analytical applications are described. The aim is to provide practical background information for the development and optimization of LC-MS methods.

Microchip technology in mass spectrometry

Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on-chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials.

Desorption and ionization mechanisms in desorption atmospheric pressure photoionization.

The factors influencing desorption and ionization in newly developed desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) were studied. Redirecting the DAPPI spray was observed to further improve the versatility of the technique: for dilute samples, parallel spray with increased analyte signal was found to be the best suited, while for more concentrated samples, the orthogonal spray with less risk for contamination is recommended. The suitability of various spray solvents and sampling surface materials was tested for a variety of analytes with different polarities and molecular weights. As in atmospheric pressure photoionization, the analytes formed [M + H](+), [M - H](-), M(+*), M(-*), [M - H + O](-), or [M - 2H + 2O](-) ions depending on the analyte, spray solvent, and ionization mode. In positive ion mode, anisole and toluene as spray solvents promoted the formation of M(+*) ions and were therefore best suited for the analysis of nonpolar compounds (anthracene, benzo[a]pyrene, and tetracyclone). Acetone and hexane were optimal spray solvents for polar compounds (MDMA, testosterone, and verapamil) since they produced intensive [M + H](+) ion peaks of the analytes. In negative ion mode, the type of spray solvent affected the signal intensity, but not the ion composition. M(-*) ions were formed from 1,4-dinitrobenzene, and [M - H + O](-) and [M - 2H + 2O](-) ions from 1,4-naphthoquinone, whereas acidic compounds (naphthoic acid and paracetamol) formed [M - H](-) ions. The tested sampling surfaces included various materials with different thermal conductivities. The materials with low thermal conductivity, i.e., polymers like poly(methyl methacrylate) and poly(tetrafluoroethylene) (Teflon) were found to be the best, since they enable localized heating of the sampling surface, which was found to be essential for efficient analyte desorption. Nevertheless, the sampling surface material did not affect the ionization mechanisms.

Direct Analysis of Illicit Drugs by Desorption Atmospheric Pressure Photoionization

The feasibility of desorption atmospheric pressure photoionization (DAPPI) in the direct analysis of illicit drugs was demonstrated by the analysis of confiscated drug samples of various forms such as tablets, blotter paper, and plant resin and bloom. 3,4-Methylenedioxymethamphetamine (MDMA), amphetamine, phenazepam, and buprenorphine were detected from the analyzed tablets, lysergic acid diethylamide (LSD) and bromobenzodifuranylisopropylamine (bromo-Dragonfly, ABDF) from blotter paper, and Delta(9)-tetrahydrocannabinol (THC) and cannabinol from Cannabis Sativa bloom and resin. The amphetamines, phenazepam and ABDF showed protonated molecules independent of the solvent used, whereas buprenorphine, LSD and the cannabinoids showed molecular ions with toluene and protonated molecules with acetone as the solvent.

Desorption atmospheric pressure photoionization–mass spectrometry in routine analysis of confiscated drugs

A comprehensive study was made, where desorption atmospheric pressure photoionization (DAPPI) was applied to the direct analysis of confiscated drugs and pharmaceuticals of various forms and matrices. The analyzed samples included herbal products [Catha edulis (khat), Psilocybe mushrooms, opium and Spice], designer drugs in tablet and powder form [e.g. meta-chlorophenylpiperazine (mCPP), 3-fluoromethamphetamine (3-FMA), methylenedioxypyrovalerone (MDPV) and methylone], and anabolic steroids in oil and tablets. The analyses were performed with ion trap mass spectrometer in MS and MS(2) modes and the obtained spectra were compared with GC-MS results. Contamination of the mass spectrometer was avoided by careful adjustment of the distance of the sample from the mass spectrometer inlet. DAPPI proved to be a fast and specific analysis technique, which does not require any sample preparation, and which therefore suits well to this type of forensic analysis.

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.

Environmental and food analysis by desorption atmospheric pressure photoionization‐mass spectrometry

Desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) is a versatile surface analysis technique for a wide range of analytes, especially for neutral and non-polar analytes. Here, a set of analytes typically found in environmental or food samples was analyzed by DAPPI-MS. The set included five polyaromatic hydrocarbons (PAHs), one N-PAH, one brominated flame retardant, and nine pesticides, which were studied with three different spray solvents: acetone and toluene in positive ion mode, and anisole in negative ion mode. The analytes showed [M + H](+), M(+*), and [M-H](-) ions as well as fragmentation and substitution products. Detection limits for the studied compounds ranged from 30 pg to 1 ng (from 0.14 to 5.6 pmol). To demonstrate the feasibility of the use of DAPPI-MS two authentic samples - a circuit board and orange peel - and a spiked soil sample were analyzed. Tetrabromobisphenol A, imazalil, and PAHs were observed from the three above-mentioned samples, respectively. The method is best suited for rapid screening analysis of environmental or food samples.

Infrared Laser Ablation Atmospheric Pressure Photoionization Mass Spectrometry

In this paper we introduce laser ablation atmospheric pressure photoionization (LAAPPI), a novel atmospheric pressure ion source for mass spectrometry. In LAAPPI the analytes are ablated from water-rich solid samples or from aqueous solutions with an infrared (IR) laser running at 2.94 μm wavelength. Approximately 12 mm above the sample surface, the ablation plume is intercepted with an orthogonal hot solvent (e.g., toluene or anisole) jet, which is generated by a heated nebulizer microchip and directed toward the mass spectrometer inlet. The ablated analytes are desolvated and ionized in the gas-phase by atmospheric pressure photoionization using a 10 eV vacuum ultraviolet krypton discharge lamp. The effect of operational parameters and spray solvent on the performance of LAAPPI is studied. LAAPPI offers ~300 μm lateral resolution comparable to, e.g., matrix-assisted laser desorption ionization. In addition to polar compounds, LAAPPI efficiently ionizes neutral and nonpolar compounds. The bioanalytical application of the method is demonstrated by the direct LAAPPI analysis of rat brain tissue sections and sour orange (Citrus aurantium) leaves.

Gas chromatography/mass spectrometry of polychlorinated biphenyls using atmospheric pressure chemical ionization and atmospheric pressure photoionization microchips.

Gas chromatography (GC) and ion trap mass spectrometry (MS) were combined with microchip atmospheric pressure chemical ionization (microAPCI) and microchip atmospheric pressure photoionization (microAPPI) sources. Selected polychlorinated biphenyls (PCBs, IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180) were analyzed by GC/microAPCI-MS and GC/microAPPI-MS to demonstrate the applicability of the miniaturized ion sources in negative ion mode analysis. The microAPCI and microAPPI methods were evaluated in respect of detection limit, linearity and repeatability. The detection limits for the PCB congeners were somewhat lower with microAPCI than with microAPPI, whereas microAPPI showed slightly wider linear range and better repeatability. With both methods, the best results were obtained for highly chlorinated or non-ortho-chlorinated PCBs, which possess the highest electron affinities. Finally, the suitability of the GC/microAPPI-MS method for the analysis of PCBs in environmental samples was demonstrated by analyzing soil extracts, and by comparing the results with those obtained by gas chromatography with electron capture detection (GC/ECD).

Analysis of street market confiscated drugs by desorption atmospheric pressure photoionization and desorption electrospray ionization coupled with mass spectrometry

The rapid screening analysis of drugs has a wide range of applications in the field of forensics and toxicology. Since the introduction of ambient desorption/ ionization techniques, rapid screening of drugs bymass spectrometry (MS) has become possible. Desorption electrospray ionization (DESI), direct analysis in real time (DART), atmospheric solids analysis probe (ASAP), and desorption sonic spray ionization (DeSSI) have all been used in the analysis of commercial and illicit drugs. In DESI, charged solvent droplets, generated by a high gas flow and an electric potential between the sprayer and the mass spectrometer, desorb the analytes from a solid surface as a result of electrostatic and pneumatic forces, and in positive ion mode mainly [MþH]þ ions are produced. Another recently reported desorption/ionization method feasible for drug analysis is desorption atmospheric pressure photoionization (DAPPI). DAPPI is a thermal desorption/ionization method, in which the heated jet, produced by a microchip nebulizer and consisting of nitrogen and spray solvent vapor, is directed towards the sample in order to desorb the analytes from the sampling surface. Desorbed species are then photoionized in the gas phase and ions are analyzed with a mass spectrometer. In the positive ion mode DAPPI produces Mþ . or [MþH]þ ions depending on the analyte and the spray solvent used. Tablets and cream formulations can be analyzed as such by DESI-MS or DAPPI-MS but, due to the nature of desorption/ionization methods, powdered samples need to be compressed to prevent puffing of the powder. In this letter we describe rapid screening applications for powdered samples of drugs of abuse. Instead of being compressed, the drug samples were dissolved in solvent prior to analysis, and analyzed by both DAPPI-MS and DESI-MS. Both methods were observed to be feasible for the rapid detection of drug compounds. The methods are faster than conventional infusion studies with atmospheric pressure photoionization mass spectrometry (APPI-MS) or electrospray ionization mass spectrometry (ESI-MS) and, in addition, both are feasible for very small amounts of sample. The sensitivity of the analysis and the ions generated depended on the analyte, the ionization method, and desorption/ionization conditions. The confiscated drug samples included powders of amphetamine, cocaine, heroin, methamphetamine, and methylenedioxymethamphetamine (MDMA) (Table 1). The samples also contained cutting agents. The powdered drug samples were dissolved in methanol, after which the stock solutions (0.5mg/mL) were further diluted with water/methanol (50:50) to working solutions of 10mg/ mL. For the analysis, 1mL of the sample solution per one sampling spot was pipetted on the sampling surface (poly(methyl methacrylate), PMMA) and left to dry. The actual amount of the analyte in one sample spot was then 2.5–7.8 ng depending on the purity of the drug sample (Table 1). Dried droplets of the samples were desorbed from the PMMA sampling surface, ionized, and analyzed by an ion trap mass spectrometer equipped with a capillary extension (Esquire 3000þ, Bruker Daltonics, Bremen, Germany) operating in positive ion mode. Custom-made DAPPI and DESI sources were used in the analysis. The DAPPI source consisted of a nebulizer microchip, which produced a heated plume to desorb the analytes from the sampling surface into the gas phase, and of a krypton discharge lamp (Cathodeon, Cambridge, UK), which produced photons for photoionization. terscience.wiley.com) DOI: 10.1002/rcm.4005 The heating power of the microchip was 4.5W, which corresponds to a plume temperature of approximately 2208C at 10mm distance, or approximately 3008C on the sampling surface at 4mm distance. The spray solvents used in DAPPI were HPLC grade acetone (Mallinckrodt Baker B.V., Deventer, The Netherlands) and toluene (Labscan, Dublin, Ireland). The DAPPI spray solvent flow rate was 10mL/min. A description of the detailed structure of the ion source is presented elsewhere. In the DESI source, spray solvent was introduced using a silica capillary and spray gas was introduced coaxially at approx. 10 bar pressure. The DESI spray solvent line was grounded and a voltage of 4 kV was applied to the capillary extension of the mass spectrometer. The DESI spray solvent consisted of water (purified with a Milli-Q purifying system, Millipore, Molsheim, France) and methanol (Mallinckrodt Baker B.V.) in the ratio 50:50 with 0.1 vol-% addition of formic acid (99%, Acros Organics, Geel, Belgium). The DESI spray solvent flow rate was 3mL/ min. In both ion sources the plumewas directed onto the sampling surface at 458 angle. The sample spot was placed at a distance of 3mm from the tip of the capillary extension of the mass spectrometer, and the distance between the spray and the sampling surface was 3mm. Nitrogen was used as the spray gas in both techniques. The same powder samples were also identified by gas chromatography/mass spectrometry (GC/MS; HP 6890 gas chromatograph/HP 5973 MSD quadrupole mass spectrometer; Agilent Technologies, Waldbronn, Germany) and quantified by liquid chromatography with UV detection (LC/UV; HP 1100, Agilent Technologies, Santa Clara, CA, USA) (amphetamine and metamphetamine) or gas chromatography with flame ionization detection (GC/FID; HP 6890, Agilent Technologies, Waldbronn, Germany) (cocaine and heroin) to obtain reference data from the samples and the analyte mass percentages reported in Table 1. All the active compounds found by GC/MS analysis were also observed in the analysis by DAPPI-MS and DESI-MS (Table 1). The identities of