Positive SIMS Research Articles

Comparison of static and dynamic mode in the electrochemical oxidation of fesoterodine with the use of experimental design approach

Electrochemical conversion of fesoterodine to one of its oxidation products was evaluated with the application of the wall-jet flow cell. A traditional, “static” mode of electrolysis was compared with the “dynamic” mode of cell performance. For statistical assessment of the data, experiments were planned and performed with the application of design of experiments approach, namely Taguchi L18 design. After screening phase, the experimental settings were broadened or adjusted according to the results and optimization was performed. All of the samples were electrolysed with the use of chronoamperometric method in a three electrode system. The electrolysed samples were analysed using UHPLC-PDA-QDA method. The chromatographic run was performed in gradient elution with the application of C8 column. The response was expressed as % area of the main peak found with the PDA detection method whereas QDA detector was used in positive SIM mode for structural confirmation. All data obtained for both screening and optimization were treated together and linear models were adjusted. The use of large-surface glassy carbon electrode along with pH~7 were found to be the most significant factors influencing electrochemical oxidation of fesoterodine in both modes. The major differences were identified in terms of voltage applied to the electrodes which yielded the highest amounts of oxidation product. Evolution of electrochemical methods may serve as complementary technique in stress degradation studies in pharmaceutical industry.

Determination of corticosterone from rat hair samples by HPLC-MS method

Abstract Corticosterone is an adrenocortical steroid hormone with glucocorticoid and mineralocorticoid effects. Based on previous studies, the plasma level of corticosterone correlates with the stress exposure of rodents. Because the half-life of corticosterone in blood is short, its plasma concentration can be used as an acute stress marker. But hair is accumulating the systemic and locally produced corticosterone, therefore it can be used to study chronic stress. However, the accurate quantification of corticosterone is an analytical challenge owing to the very low amount of hormone found in a complicated biological matrix. The high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) can provide the required selectivity and sensitivity for this purpose. Currently published methods for corticosterone quantification involve complicated sample preparation and long run time. Accordingly, the aims of the study were to simplify the extraction method of the corticosterone from rat hair samples and to develop an optimized HPLC-MS method for the accurate quantification. The rat hair samples were washed with methanol, dried and cut, then extracted with methanol at room temperature for 24 hours. The lipids were precipitated with formic acid aqueous solution and eliminated by centrifugation. The corticosterone was separated from other compounds with reverse phase chromatography using acetonitrile and 0,1% aqueous solution of formic acid as mobile phase. The detection was performed in positive SIM mode measuring the 347 m/z molecular ion. A six point calibration was performed in the range of 0,5-20 ng/ml, the accuracy was tested with quality control samples at two different concentration level. The total run time is only 4,2 minutes and the lower limit of quantification (LLOQ) is 0,5 ng/ml, with 10 pg absolute sensitivity. By determining the quantity of the hormone for a well-defined hair region, based on the speed of hair growth, we can characterize the retrospective stress exposure of the animals in different conditions.

Chemical imaging of molecular changes in a hydrated single cell by dynamic secondary ion mass spectrometry and super-resolution microscopy.

Chemical imaging of single cells at the molecular level is important in capturing biological dynamics. Single cell correlative imaging is realized between super-resolution microscopy, namely, structured illumination microscopy (SIM), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) using a multimodal microreactor (i.e., System for Analysis at the Liquid Vacuum Interface, SALVI). SIM characterized cells and guided subsequent ToF-SIMS analysis. Lipid fragments were identified in the cell membrane via dynamic ToF-SIMS depth profiling. Positive SIMS spectra show intracellular potassium and sodium ion transport due to exposure to nanoparticles. Spectral principal component analysis elucidates differences in chemical composition among healthy alveolar epithelial mouse lung C10 cells, cells that uptake zinc oxide nanoparticles, and various wet and dry control samples. The observation of Zn(+) gives the first direct evidence of ZnO NP uptake and dissolution by the cell membrane. Our results provide submicron chemical mapping for investigating cell dynamics at the molecular level.

Tandem MS and C60 SIMS for the identification and characterization of lipids

The tandem MS capability of a C60‐Qstar hybrid instrument was utilized for the characterization of glycerophosphocholine (GPC) lipids in positive ion mode SIMS. In general, the tandem MS of lipids is facilitated by cationization or reaction with alkali metal salts. Thus, the lipids were treated with LiTFA salt (lithiation) prior to mass spectrometric analysis. As a result of the sample treatment, cationized lipid molecular ions with lithium adducts were formed and were revealed by mass shifts of 6 Da relative to unreacted species in the SIMS spectra. The lithiated molecular ions of GPCs were then subjected to collision‐induced dissociation (CID) in tandem MS mode. Upon CID, fragments specifying the fatty acid and head group composition of the GPC lipid were generated and could be used for its structural characterization and identification. In addition, a more significant observation was revealed in the time‐of‐flight‐SIMS spectral data of the lithiated GPC. Here, we found that fragmentation was enhanced, and fragment ions similar to those produced by CID were present in the SIMS spectra. The implications of these results are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

TOF‐SIMS VG Ionex IX23LS: upgrade and application for the urinary stones analysis

TOF‐SIMS VG Ionex IX23LS with upgraded data acquisition and control system was used to study the real urinary stones along with calcium oxalate (COX) and four different calcium phosphate (CP) references. Reliable phase identification of CPs was achieved in the positive SIMS mode on basis of the PO+/POH+ and CaPO2+/Ca2O+ peak ratios. In real urinary stones, pure COX was distinguished from calcium phosphates with confidence via the presence of its characteristic ion peaks. We also quantified the calcium phosphate in the human calculi containing calcium oxalate as major or minor component, which is of a great interest for medical community. Copyright © 2012 John Wiley & Sons, Ltd.

HPLC–MS analysis of iodotyrosines produced by sample hydrolysis: A simple method for monitoring iodinated casein in feed premixes

A new and simple HPLC–MS method was developed for monitoring iodinated casein in feed premixes. In this method, feed premixes were hydrolyzed, and the iodotyrosines thus released were analyzed. Sample pretreatment included precipitation of transition metals ions with Na 2S, hydrolysis with sodium hydroxide, and cleaning up with an Oasis SAX cartridge. Gradient elution was carried out on a C 18 column with water (containing 0.1% formic acid) and acetonitrile. Ion detection was performed using ESI positive SIM at m/ z 262, 308, 388, and 434. Iodinated casein levels were monitored by qualitative analysis of the iodotyrosines released upon sample hydrolysis and by quantifying the 3,5-diiodotyrosine released. The validation data demonstrated that the method was selective and sensitive (≤0.2 mg g −1) for iodinated casein and had acceptable accuracy (recoveries: 81.3–106.7%) and precision (RSD: 1.7–16.0%).

A quantitative HPLC–MS method for the simultaneous determination of testosterone, 11-ketotestosterone and 11-β hydroxyandrostenedione in fish serum

A simple and novel HPLC–MS method for the simultaneous quantification of testosterone, 11-ketotestosterone, and 11β-hydroxyandrostenedione in fish serum was developed and validated. Separation was achieved on a C-18 column using a water–acetonitrile mobile-phase with a cycle time of 12min. Ion detection was performed using ESI positive SIM at [M+H] (m/z 303, 303, 289). The linear ranges (0.2–50ng/ml), limits of detection (0.1–0.2ng/ml) and quantification (0.2–0.5ng/ml) were established. The method was validated by measuring the three androgens in goldfish sera, displaying comparable values to those reported by other analytical techniques (RIA, EIA).

Bioavailability of water-soluble CoQ10 in beagle dogs

The bioavailability of a novel water-soluble inclusion complex of CoQ10, prepared in our laboratory was determined and compared with the bioavailability of commercially available oil-based form of CoQ10. Experimental work consisted of single dose comparative bioavailability study on seven beagle dogs, with a 14-day washout period between treatments. Identification and quantification of CoQ10 was done with HPLC–MS method using positive APCI ionization and SIM mode, M + m/ z 863.4. The bioavailability results confirm that the water-soluble formulation has nearly three times higher AUC (0–48 h) , two times higher C max, and T max is shortened from 6 to 4 h.

Single quadrupole mass spectrometry for pre-clinical pharmacokinetic analysis: Quantitation of carvedilol in dog plasma

The pharmaceutical industry standard for bioanalysis is LC/MS/MS. There are, however, many instances where a single quadrupole detector could successfully be used to provide adequate sensitivity and selectivity for quantitation of drug substances in biological matrices. This paper presents one example of how a single quadrupole detector can be employed in a sensitive and selective analytical method for quantitation of carvedilol. A Synergi Hydro-RP (50 mm × 2 mm i.d.; 4 μm) column was used with acetonitile:water:formic acid mobile phase (32:68:0.01, v/v) at a flow rate of 200 μL/min into a single quadrupole mass spectrometer with an electrospray interface in the positive SIM mode. Using a 300 μL plasma aliquot and a liquid–liquid extraction procedure the limit of quantitation for the assay was 1 ng/mL. The assay utility was demonstrated in the analysis of carvedilol pharmacokinetic profiles in beagle dogs following oral carvedilol administration.

Blue natural organic dyestuffs—from textile dyeing to mural painting. Separation and characterization of coloring matters present in elderberry, logwood and indigo

Natural dyestuffs used for painting or dyeing of textiles are complex mixtures of compounds of various chemical properties. Proper identification of the dye used by a painter and, even better, its origin is possible only when its compositional 'fingerprint' can be evaluated. For this reason gradient program for liquid chromatographic separation of 16 color compounds--components of natural blue dyes: elderberry, logwood and indigo--has been developed. Two detector systems were used simultaneously: UV-Vis spectrophotometry (at 280, 445, 520 and 600 nm) and ESI mass spectrometry (positive and negative SIM mode). It was found that fragmentation observed in ESI-MS is affected not only by ion source parameters, but also by chromatographic conditions, especially in case of the less stable substances: cyanidin glucosides, tannic acid, rutin and hematoxylin. Examination of characteristic dissociation pathways of the compounds under investigation after direct admission into ion source or after chromatographic separation allowed to select proper ions for SIM detection and to develop novel and efficient reversed phase high performance liquid chromatographic (RP-HPLC)-UV-Vis/ESI-MS method for the analysis of natural blue dyes. The procedure was successfully applied for identification of indigotin and carminic acid-main colorants extracted from a fiber taken from the blue-red 'Italian' tapestry (the collection of the National Museum in Warsaw, Poland).

Capillary Electrochromatography−Mass Spectrometry of Zwitterionic Surfactants

This work describes the on-line hyphenation of a packed capillary electrochromatography (CEC) column with an internally tapered tip coupled to electrospray ionization-mass spectrometry (ESI-MS) and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) for the analysis of betaine-type amphoteric or zwitterionic surfactants (Zwittergent). A systematic investigation of the CEC separation and MS detection parameters comparing ESI and APCI is shown. First, a detailed and optimized manufacturing procedure for fabrication of the CEC-MS column with a reproducible internally tapered tip (7-9 microm) is presented. Next, the optimization of the separation parameters by varying the C(18) stationary-phase particle size (3 versus 1.5 microm), as well as mobile-phase composition including acetonitrile (ACN) volume fraction, ionic strength, and pH is described. The optimized separation is achieved using 3-microm C(18) packing with 75% ACN (v/v), 5 mM Tris at pH 8.0. Optimization for on-line CEC-ESI-MS detection is then done varying both the sheath liquid and spray chamber parameters while evaluating the use of random versus structured factorial table experimental designs. The more structured approach allows fundamental analysis of individual ESI-MS parameters while minimizing CEC and MS equilibration time between settings. A comparison of CEC-ESI-MS to CEC-APCI-MS using similar sheath and spray chamber conditions presents new insight for coupling of CEC to APCI-MS. The sheath liquid flow rate required to maintain adequate sensitivity is much higher in APCI source (50 microL/min) as compared to the ESI source (3 microL/min). The on-line mass spectra obtained in the full scan mode show that fragmentation in the two sources occurs at different positions on the Zwittergent molecules. For ESI-MS, the protonated molecular ion is always highest in abundance with minor fragmentation occurring due to the loss of the alkyl chain. In contrast, the APCI-MS spectra show that the highest abundant ion resulted by elimination of propane sulfonate from the Zwittergent molecule. A comparison of the sensitivity between the two sources in positive ionization SIM mode shows that CEC-ESI-MS provides an impressive limit of detection (LOD) of 5 ng/mL, which is at least 3 orders of magnitude lower than CEC-APCI-MS (LOD 100 microg/mL). Finally, the optimized CEC-MS methods comparing ESI and APCI are applied for separation and structural characterization of a real industrial zwittergent sample, Rewoteric AM CAS.

Detection of the diatomic dications SiH 2+ and AlH 2+

The diatomic dications SiH 2+ and AlH 2+ were produced by Ar + sputtering of a hydrogenated amorphous silicon (a-Si:H) layer deposited on an Al substrate. These exotic dications were observed in positive SIMS mass spectra taken at low ( 30 Si 1 H 2+ at m/ z 15.5) and at high mass resolution. More intense signals of SiH 2+ or AlH 2+ could be produced by toluene (C 7H 8) vapor flooding of an Ar + bombarded Si or Al surface. The ion energy distributions of SiH 2+ for both a-Si:H/Al and toluene-flooded Si show that it is formed at or near the sputtered surface. Ion formation by collisional processes in the gas phase several micrometers away from the surface is found to be negligible. Exposure of the sputtered a-Si:H surface to oxygen reduced the intensity of SiH 2+. This argues strongly against an association of Si + and H + at or near the surface. It is conjectured that ion formation of SiH 2+ may be caused by Auger shake-off decay of Si2p core-excited molecules of SiH * a few nanometers in front of the sputtered surface.

Detection of the diatomic dications SiH2+ and AlH2+

The diatomic dications SiH2+ and AlH2+ were produced by Ar+ sputtering of a hydrogenated amorphous silicon (a-Si:H) layer deposited on an Al substrate. These exotic dications were observed in positive SIMS mass spectra taken at low (30Si1H2+ at m/z 15.5) and at high mass resolution. More intense signals of SiH2+ or AlH2+ could be produced by toluene (C7H8) vapor flooding of an Ar+ bombarded Si or Al surface. The ion energy distributions of SiH2+ for both a-Si:H/Al and toluene-flooded Si show that it is formed at or near the sputtered surface. Ion formation by collisional processes in the gas phase several micrometers away from the surface is found to be negligible. Exposure of the sputtered a-Si:H surface to oxygen reduced the intensity of SiH2+. This argues strongly against an association of Si+ and H+ at or near the surface. It is conjectured that ion formation of SiH2+ may be caused by Auger shake-off decay of Si2p core-excited molecules of SiH* a few nanometers in front of the sputtered surface.

Improved charge neutralization method for depth profiling of bulk insulators using O 2+ primary beam on a magnetic sector SIMS instrument

Use of electrons for charge neutralization during positive secondary ion SIMS analysis of insulators has typically been achieved using coincident primary ion and electron beams. The normal incidence electron gun on CAMECA magnetic sector SIMS instruments can effectively eliminate sample charging during analysis of thin insulating films if the electron energy is sufficient to penetrate the film. However, positive secondary ion SIMS bulk insulator analysis using this instrument can be difficult, especially if high sputtering rates are required. A neutralization method has been developed utilizing electron beam impact of a region adjacent to the sputtered area. Prior to analysis, the surface of the sample is coated with gold which provides a conductive surface layer and which has a high secondary and backscattered electron yield. Results have been obtained showing excellent neutralization for a variety of bulk insulators including glass, silica, alumina, and lithium niobate. Sputtering rates exceeding 2 nm/s have been achieved in bulk silica. The technique should be applicable to minerals and possibly for other materials in cases where the analyzed area cannot be directly irradiated with an electron beam.

CIGS2 Thin Film Solar Cells on Stainless Steel Foil

ABSTRACTCuIn1−xGaxS2 (CIGS2) thin-film solar cells are of interest for space power applications because of the near optimum bandgap for AM0 solar radiation in space. CuIn1−xGaxSe2−ySy (CIGS) and CIGS2 solar cells are expected to be superior to Si and GaAs solar cells for the space missions especially in terms of the performance at the end of low earth orbit (LEO) mission. Ultra-lightweight thin-film solar cells deposited on flexible stainless steel (SS) foils have a potential for achieving high specific power.Magnetron-sputter-deposition parameters of molybdenum back-contact layer were optimized so as to minimize residual stress. Cu-rich Cu-Ga/In layers were sputter-deposited on unheated Mo-coated SS foils from CuGa(22%) and In targets. Well-adherent, large (3 μm), compact-grain Cu-rich CIGS2 films were obtained by sulfurization in a Ar:H2S 1:0.04 mixture and argon flow rate of 650 sccm, at the maximum temperature of 475° C for 60 minutes with intermediate 30 minute annealing step at 120° C. p-type CIGS2 thin films were obtained by etching away the Cu- rich layer segregated at the surface in a dilute KCN solution. XRD analysis of a CIGS2 film on SS foil revealed growth of chalcopyrite CIGS2 phase having ao= 5.519 Å and co= 11.125 Å and {112} preferred orientation. Positive SIMS depth profile of CIGS2 film showed gallium concentration increasing toward the back contact.Solar cells were completed by deposition of CdS heterojunction partner layer by chemical bath deposition, transparent-conducting ZnO/ZnO:Al window bilayer by RF sputtering, and vacuum deposition of Ni/Al contact fingers through metal mask. PV parameters of a CIGS2 solar cell on SS flexible foil measured under AM 0 conditions at the NASA GRC were: Voc = 802.9 mV, Jsc = 25.07 mA/cm2, FF = 60.06%, and η = 8.84%. For this cell, AM 1.5 PV parameters measured at NREL were: Voc = 788 mV, Jsc = 19.78 mA/cm2, FF = 59.44%, η = 9.26%. Quantum efficiency curve showed a sharp QE cutoff equivalent to CIGS2 bandgap of ∼1.50 eV, fairly close to the optimum value for efficient AM0 PV conversion in the space.

Sulfonation of Poly(N-vinylcarbazole) Studied by Combined Time-of-Flight Secondary Ion Mass Spectrometry and X-ray Photoelectron Spectroscopy

A series of sulfonated poly(N-vinylcarbazole) (PVK) samples have been systematically studied by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS). Negative TOF-SIMS results provided unambiguous evidence that sulfonate groups are chemically attached to the carbazole moiety of PVK. The positive SIMS spectrum of PVK was, however, little affected by the sulfonation reaction. The degree of sulfonation was quantitatively determined by XPS. Therefore, the combination of TOF-SIMS and XPS is useful to follow the sulfonation reaction, both qualitatively and quantitatively. The SIMS intensities of some characteristic fragments are linearly related to the degree of sulfonation, suggesting that quantitative analysis is possible from TOF-SIMS data.

Positive secondary ion mass spectrum of poly(methyl methacrylate): a high mass resolution ToF-SIMS study

The positive SIMS spectrum of poly(methyl methacrylate) (PMMA) has been obtained with a mass resolution in excess of 8000 and all the components assigned up to m/z 200 based on accurate mass measurements. Aspects of the interpretation of the spectrum, previously based on quadrupole SIMS data from a number of acrylic polymers, need to be revised significantly. In particular, the spectrum is dominated by oxygen-containing fragments derived from oligomeric units rather than hydrocarbon fragments derived from the polymer backbone. To aid further the understanding of the fragmentation of acrylic polymers, a less-detailed study of poly(methyl acrylate) has also been carried out. Copyright © 2000 John Wiley & Sons, Ltd.

Chemical behaviour of zirconium oxychloride octahydrate and acetic acid in precursor solution for zirconia film formation on glass

Precursor solutions for zirconia films on soda lime silica glass substrate were prepared from zirconium oxychloride octahydrate (ZOO) and acetic acid (HOAC) maintaining the mol ratios, [HOAC]/[ZOO]=2, 4, 6, 8 and 10. A characteristic UV absorption band at ∼280 nm in the ∼120h aged precursor solutions was identified for acetate group of the zirconium acetato complexed species. The presence of acetate ligand coordinated with either ZrOOH+ or [Zr4(OH)8]8+ or with both was predicted by the studies of UV spectra of aged solutions and FTIR spectra of unbaked films on silicon wafer. Dipping technique was followed for film formation. Thicknesses and refractive indices of the baked (450°±5°C) films were in the ranges 1818±20 A and 1.702–1.762 respectively. The positive SIMS experiment on two typical films baked at 450°±5°C derived from the precursors with [HOAC]/[ZOO]=2 and 6, detected the ionic species, Zr+, ZrO+, ZrO2+, Na+, Ca+, Fe+, H+ while the negative SIMS detected O− and Cl−. The relative contents of the ionic species with respect to Zr+ were dependent on the acid content of the precursors. Reflection (%) of the baked films in the UV region was also dependent on the acid content of the precursors. Electron diffraction pattern of the typical baked film derived from the precursor with [HOAC]/[ZOO]=2 exhibited meta-stable cubic phase of zirconia and the grains were found to be elongated (aspect ratio, 2.00–2.33).

Surface characterization of tyrosine-derived polycarbonates

The surfaces of five biodegradable tyrosine-derived polycarbonates were studied using contact angle measurements, ESCA, and static SIMS. The wettability, critical surface tension, and polarity of these polymers decreased with increasing chain length of the pendent alkyl groups. Surface elemental composition, as determined by ESCA, was consistent with the stoichiometry of the repeat unit of the polymers. High-resolution C1s, O1s, and N1s ESCA spectra also showed results consistent with the different bonding states of these elements in the polymer repeat unit. In both positive and negative ion spectra, SIMS experiments showed fragment ions characteristic of the polymer backbone. Fragment ions characteristic of the pendent groups were identified in the negative ion SIMS spectra only, while the positive SIMS spectra provided a characteristic fingerprint for each polymer. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 63: 1467–1479, 1997

Sputtering investigation of boron nitride with secondary ion and secondary neutral mass spectrometry

Sputtering of boron nitride with xenon ions was investigated using secondary ion (SIMS) and secondary neutral (SNMS) mass spectrometry. The ions generated from the ion gun were incident on the target at an angle of 50° with respect to the surface normal. The energy of ions ranged from 100 eV to 3 keV. A flood electron gun was used to neutralize the positive charge buildup on the target surface. The intensities of sputtered neutral and charged particles, including single atoms, molecules, and clusters, were measured as a function of ion energy. Positive SIMS spectra were dominated by the two boron isotopes whereas BN− and B− were the two major constituents of the negative SIMS spectra. Nitrogen could be detected only in the SNMS spectra. The intensity–energy curves of the sputtered particles were similar in shape. The knees in p-SIMS and SNMS intensity–energy curves appear at around 1 keV, which is significantly higher than the 100–300 eV energy range at which knees appear in the sputtering of medium and heavy elements by ions of argon and xenon. This difference in the position of the sputter yield knee between boron nitride and heavier targets is due to the reduced ion energy differences.