Comparison of electrospray ionization,atmospheric pressure chemical ionization and atmospheric pressure photoionization for determining estrogenic chemicals in water by liquid chromatography tandem mass spectrometry with chemical derivatizations

This study compared the sensitivities and matrix effects of four ionization modes and four reversed-phase liquid chromatographic (LC) systems on analyzing estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), 4-nonylphenol (NP), 4-tert-octylphenol (OP), bisphenol A (BPA) and their derivatives of dansyl chloride or pentafluorobenzyl bromide (PFBBr) in water matrixes using a triple-quadrupole mass spectrometer with selected reaction monitoring (SRM). The four probes were electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI) and APCI/APPI; the four LC systems were ultra-performance liquid chromatography (UPLC) with or without post-column split, a mixed-mode column and two-dimensional LC (2D-LC). Dansylated compounds with ESI at UPLC condition had the most intense signals and less matrix effects of the various combinations of ionization and LC systems. The on-column limits of detection (LODs) of dansylated estrogens by SRM were 0.05–0.20 pg, and the LODs in sewage treatment plant effluent and in river water were 0.23–0.52 and 0.56–0.91 ng/L, respectively. The LODs using selected ion monitoring (SIM) reached low ng/L levels in real samples and measured concentrations were comparable with those of SRM.     

Determination of selected sulfonamide antibiotics and trimethoprim in manure by electrospray and atmospheric pressure chemical ionization tandem mass spectrometry

A method for the determination of sulfonamides and trimethoprim in the complex matrix liquid manure has been developed using reversed-phase liquid chromatography and atmospheric pressure chemical ionization (APCI) tandem mass spectrometry. A comparison was made between electrospray and atmospheric pressure chemical ionization. APCI proved to be more robust and less sensitive to matrix effects. High-performance liquid chromatographic (HPLC) separation of the analytes was achieved in less than 7 min. The compounds were extracted with ethyl acetate and the extracts were cleaned up by solid-phase extraction on an aminopropyl column. Recoveries were not dependent on the concentration level. The mean recoveries were as follows: trimethoprim 79.0%, sulfadiazine 80.5%, N(4)-acetylsulfadiazine 91.0%, sulfamerazine 78.6%, sulfadimidine 77.2% and sulfamethoxazole 82.8%. Linearity was established over a concentration range of 5 to 5000 microg/kg with correlation coefficients greater than 0.99. The method had a limit of quantitation (LOQ) of 5 microg/kg manure.     

Atmospheric pressure chemical ionization of fluorinated phenols in atmospheric pressure chemical ionization mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) for fluorinated phenols (C6H5-xFxOH Where x = 0-5) in nitrogen with Cl- as the reagent ion yielded product ions of M Cl- through ion associations or (M-H)- through proton abstractions. Proton abstraction was controllable by potentials on the orifice and first lens, suggesting that some proton abstraction occurs through collision induced dissociation (CID) in the interface region. This was proven using CID of adduct ions (M Cl-) with Q2 studies where adduct ions were dissociated to Cl- or proton abstracted to (M-H)-. The extent of proton abstraction depended upon ion energy and structure in order of calculated acidities: pentafluorophenol > tetrafluorophenol > trifluorophenol > difluorophenol. Little or no proton abstraction occurred for fluorophenol, phenol, or benzyl alcohol analogs. Ion mobility spectrometry was used to determine if proton abstraction reactions passed through an adduct intermediate with thermalized ions and mobility spectra for all chemicals were obtained from 25 to 200 degrees C. Proton abstraction from M Cl- was not observed at any temperature for phenol, monofluorophenol, or difluorophenol. Mobility spectra for trifluorophenol revealed the kinetic transformations to (M-H)- either from M Cl- or from M2 Cl- directly. Proton abstraction was the predominant reaction for tetra- and penta-fluorophenols. Consequently, the evidence suggests that proton abstraction occurs from an adduct ion where the reaction barrier is reduced with increasing acidity of the O-H bond in C6H5-xFxOH.     

Fragmentation study of protonated chalcones by atmospheric pressure chemical ionization and tandem mass spectrometry

Fragmentation mechanisms of protonated chalcone and its derivatives with different functional groups were investigated by atmospheric pressure chemical ionization with tandem mass spectrometry (MS/MS). The major fragmentation pathways were loss of the phenyl group from the A or B ring, combined with loss of CO. Losses of H(2)O and CO from the precursor ions of [M+H](+) are proposed to occur via rearrangements. Elimination of water from protonated chalcones was observed in all the title compounds to yield a stable ion but it was difficult to obtain skeletal fragmentation of a precursor ion. Loss of CO was found in the MS/MS spectra of all the compounds except the nitro-substituted chalcones. When the [M+H--CO](+) ion was fragmented in the MS/MS experiments, there were distinctive losses of 15 and 28 Da, as the methyl radical and ethylene, respectively. The ion at m/z 130, found only in the nitro-substituted chalcones, was assigned as C(9)H(6)O by Fourier transform ion cyclotron resonance (FTICR)-MS/MS; m/z 130 is a common fragment ion in the electron ionization (EI) spectra of chalcones. In order to more easily distinguish the constitutional isomers of these chalcones, breakdown curves were produced and these provided strong support in this study.     

Study of atmospheric pressure chemical ionization of PETN by ion mobility spectrometry/tandem mass spectrometry

We present the results of studying the effects of temperature and humidity of the reaction medium and the intensity of ultraviolet radiation on the atmospheric pressure chemical ionization of Penthrite. The peculiarities of the ion mobility spectra of this compound obtained by ion mobility spectrometry-tandem mass spectrometry are analyzed.     

Analysis of polycyclic aromatic hydrocarbons by liquid chromatography/tandem mass spectrometry using atmospheric pressure chemical ionization or electrospray ionization with tropylium post-column derivatization

Polycyclic aromatic hydrocarbons (PAHs) with four to six rings are potent carcinogens. This study analyzed ten of the sixteen US EPA priority PAHs using reversed-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) in selected reaction monitoring mode with two ionization sources: positive atmospheric pressure chemical ionization (APCI+) or positive elecrtrospray ionization (ESI+) with tropylium post-column derivatization. Several factors were investigated, including mobile phases, stationary phases of columns and chromatographic temperature, to determine how optimal separation and sensitivity might be achieved. Methanol used as an organic mobile phase provided better sensitivities for most PAHs than acetonitrile, although some PAHs co-eluted. Acidic buffers did not increase analyte signals. Use of Restek Pinnacle II PAH columns (250 x 4.6 mm or 250 x 2.1 mm, 5 microm) with water/acetonitrile gradient at 27 degrees C made possible a good separation of the ten analytes. [M]+. were the best precursor ions in both APCI and ESI, although fluoranthene could not be detected in ESI mode when tropylium post-column derivatization was performed. [M-28]+ and [M-52]+ were the major product ions of PAHs after collision-induced dissociation, a result of neutral losses of C(2)H(4) and (C(2)H(2))(2), respectively. Chromatographic separation for PAH isomers was crucial because the mass spectra were so similar that even MS/MS could not distinguish them from each other. The recoveries of sample preparations of PAHs spiked onto air-sampling filters ranged between 77.5 and 106% with relative standard deviations between 1.1 and 15.9%. This method was validated by analyzing NIST SRM 1649a (urban dust), producing results comparable with the certified PAH concentrations. The detection limits using APCI and ESI interfaces, defined as three times the noise levels, ranged between 0.23 and 0.83 ng and between 0.16 and 0.84 ng of on-column injection, respectively.     

Liquid chromatography with atmospheric pressure chemical ionization and electrospray ionization mass spectrometry of flavonoids with triple-quadrupole and ion-trap instruments

With 15 flavonoids as test compounds, the analytical performance of four modes of LC-MS, multiple MS (MSn) and tandem MS operation (atmospheric pressure chemical ionization (APCI), electrospray ionization, positive and negative ionization) was compared for two mass spectrometers, a triple-quadrupole and an ion-trap instrument. Two organic modifiers, methanol and acetonitrile, and two buffers, ammonium acetate and ammonium formate, were used. In general, the use of APCI in the negative ion mode gave the best response, with the signal intensities and the mass-spectral characteristics not differing significantly between the two instruments. The best results were obtained when methanol-ammonium formate (pH 4.0) was used as LC eluent. Under optimum conditions full-scan limits of detection of 0.1-30 mg/l were achieved in the negative APCI mode. Here it needs to be emphasized that up to 2-order response differences were found both between analytes and between modes of ionization. This implies that one should be very cautious when interpreting data on the screening of real-life samples. The main fragmentations observed in the MSn spectra on the ion-trap, or the tandem MS spectra on the triple-quadrupole were generally the same. The advantage of the former approach is the added possibility to ascertain precursor-->product ion relationships.     

Probing the mechanism of the Petasis olefination reaction by atmospheric pressure chemical ionization mass and tandem mass spectrometry

Atmospheric pressure chemical ionization mass (APCI-MS) and tandem mass spectrometry (APCI-MS/MS) is used to probe the mechanism of the Petasis olefination reaction. Oxatitanacycle intermediates 4 were transferred from solution to the gas phase, detected as 4H+ by APCI-MS with characteristic Ti-isotopic patterns, and structurally characterized by APCI-MS/MS. Detection of 4H+, which upon collision activation dissociates to both 3H+ and Cp(2)TiOH+, fully supports the Hughes mechanism as depicted above. [reaction: see text]     

Analysis of benzylisoquinoline-type alkaloids by electrospray tandem mass spectrometry and atmospheric pressure photoionization

Benzylisoquinoline alkaloids found in the Papaveraceae family play a major role in pharmaceutical biology. This is the first systematic study dealing with electrospray tandem mass spectrometry (ESI-MS/MS) of all benzylisoquinolines found as biogenetic precursors of morphinan alkaloids. Tandem mass spectral data are presented for norlaudanosoline, laudanosoline, 4'-O-methyl-norlaudanosoline, 6-O-methyl-norlaudanosoline, norcoclaurine, coclaurine, N-methylcoclaurine, N-methyl-3'-hydroxycoclaurine, N-methyl-3'-O-methylcoclaurine, norreticuline and reticuline. This study compares results obtained using an ion trap mass spectrometer with those obtained using a triple quadrupole one. The results highlight the differences of the tandem-in-time versus the tandem-in-space principle, often hampering the development of ESI-MS/MS libraries. Additionally, the use of the atmospheric pressure photoionisation technique for the analysis of such substances is discussed.     

Quantitative determination of polar and ionic compounds in petroleum fractions by atmospheric pressure chemical ionization and electrospray ionization mass spectrometry

The capabilities of atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) methods for quantitative analysis of polar and ionic compounds in petroleum fractions have been examined. The requirements of the analysis for sensitivity, linear dynamic range, and structural characterization have been discussed. ESI was found to be approximately two orders of magnitude more sensitive than APCI and is most suitable for the detection of analytes in weak concentrations. Equivalent relative linear dynamic ranges were observed by the two methods (at least three orders of magnitude). For the relatively high analyte concentrations examined here (e.g., 1-100 ppm or higher), the absolute area counts increased linearly with the analyte amount only in APCI, making this method more attractive for quantitative liquid chromatography/mass spectrometry (LC/MS) applications. Nevertheless, a wider range of ionic compounds can be detected by ESI than by APCI.     

Precursor ion scan profiles of acylcarnitines by atmospheric pressure thermal desorption chemical ionization tandem mass spectrometry

The fatty acyl esters of L-carnitine (acylcarnitines) are useful biomarkers for the diagnosis of some inborn errors of metabolism analyzed by liquid chromatography/tandem mass spectrometry. In this study the acylcarnitines were analyzed by atmospheric pressure thermal desorption chemical ionization using a commercial tandem mass spectrometer (APTDCI-MS/MS). The method is based on the precursor ion scan mode determination of underivatized acylcarnitines desorbed from samples by a hot desolvation gas flow and ionized by a corona pin discharge. During desorption/ionization step the temperature induces the degradation of acylcarnitines; nevertheless, the common fragment to all acylcarnitines [MH-59](+) is useful for analyzing their profile. APTDCI parameters, including angle of collection and incidence, gas flows and temperatures, were optimized for acylcarnitines. The experiments were performed drying 2 microL of an equimolar mixture of acylcarnitine standards on a glass slide. The specificity was evaluated by comparing product ion spectra and the precursor ion spectra of 85 m/z of acylcarnitines obtained by the APTDCI method and by electrospray ionization flow injection analysis (ESI-FIA). The method was also employed to analyze acylcarnitines extracted from a pathological dried blood spot and a control. The method enables analysis of biological samples and recognition of some acylcarnitines that are diagnostic markers of inherited metabolic diseases. The intrinsic high-throughput analysis of the ambient desorption ionization methods offers a new opportunity either for its potential application in clinical chemistry and for the expanded screening of some inborn errors of metabolism.     

Super‐atmospheric pressure chemical ionization mass spectrometry

Super‐atmospheric pressure chemical ionization (APCI) mass spectrometry was performed using a commercial mass spectrometer by pressurizing the ion source with compressed air up to 7 atm. Similar to typical APCI source, reactant ions in the experiment were generated with corona discharge using a needle electrode. Although a higher needle potential was necessary to initiate the corona discharge, discharge current and detected ion signal were stable at all tested pressures. A Roots booster pump with variable pumping speed was installed between the evacuation port of the mass spectrometer and the original rough pumps to maintain a same pressure in the first pumping stage of the mass spectrometer regardless of ion source pressure. Measurement of gaseous methamphetamine and research department explosive showed an increase in ion intensity with the ion source pressure until an optimum pressure at around 4–5 atm. Beyond 5 atm, the ion intensity decreased with further increase of pressure, likely due to greater ion losses inside the ion transport capillary. For benzene, it was found that besides molecular ion and protonated species, ion due to [M + 2H]⁺ which was not so common in APCI, was also observed with high ion abundance under super‐atmospheric pressure condition. Copyright © 2013 John Wiley & Sons, Ltd.     

Structural determination of sphingomyelin by tandem mass spectrometry with electrospray ionization

Alkaline metal adduct ions of sphingomyelin were formed by electrospray ionization in positive ion mode. Under low energy collisionally activated dissociation (CAD), the product ion spectra yield abundant fragment ions representative of both long chain base and fatty acid which permit unequivocal determination of the structure. Tandem spectra obtained by constant neutral loss scanning permit identification of sphingomyelin class and specific long chain base subclass in the mixture. The fragmentation pathways under CAD were proposed, and were further confirmed by source CAD tandem mass spectrometry. The total analysis of sphingomyelin mixtures from bovine brain, bovine erythrocytes, and chicken egg yolk is also presented.     

Characterization of the chemical composition of a block copolymer by liquid chromatography/mass spectrometry using atmospheric pressure chemical ionization and electrospray ionization

Liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in the positive and negative ion modes was used for the characterization of a block copolymer consisting of methoxy poly(ethylene oxide) (mPEO), an epsilon-caprolactone (CL) segment and linoleic acid (LA), used as surfactant in water-based latex paints. Chromatographic separation was obtained based on the number of CL units in the polymer species and the presence of an mPEO and/or LA tail. Different ionization methods were found to be complementary and only their combination allowed the qualitative profiling of the chemical composition. The LC/MS method has proven valuable for following the reaction in time, as well as for comparison of different polymeric surfactants.     

Identification and determination of glycosides in tobacco leaves by liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry

HPLC-atmospheric pressure chemical ionization MS (HPLC-APCI-MS) was used to screen and identify glycosides in tobacco leaf. MS/MS and MS3 and photodiode array (PDA) detection were also used in the characterization. A total of 12 glycosides were found and four of them were identified based on their abundant [M + H]+ ions, UV spectra, and MS/MS analysis and they are scopolin, rutin, quercetin-3-glycoside, and kaempferol-3-rutinoside. Analytical characteristics of the method were investigated. The contents of these glycosides were obtained and compared based on the relative peak area to the internal standard in seven kinds of tobacco leaf.     

High-throughput assay of rotenone in olive oil using atmospheric pressure chemical ionization tandem mass spectrometry

A high-throughput method is presented for the determination of rotenone in contaminated matrices. The procedure involves atmospheric pressure chemical ionization tandem mass spectrometry with a triple-quadrupole instrument and the use as internal standard of a cycloadduct derivative of rotenone itself. The method was applied to the evaluation of the decay of rotenone in olives and olive oil at various times after exposure to the contaminant.