Full Mass Spectra Research Articles

Identification and Characterization of Indole and Oxindole Alkaloids from Leaves of Mitragyna speciosa Korth Using Liquid Chromatography-Accurate QToF Mass Spectrometry.

Alkaloids have been reported to be the major physiologically active constituents in Mitragyna. An analytical method was developed to provide an alternative, fast method for characterization of alkaloids from various M. speciosa samples. The separation was achieved using an RP octylsilyl (C8) column, MS detection, and a water-acetonitrile with formic acid gradient as the mobile phase. Ultra-HPLC/quadrupole time-of-flight MS analysis and characterization were performed on 12 corynanthe-type indole/oxindole alkaloids obtained from the leaves of M. speciosa Korth. The indoles and oxindoles had an open E ring with or without substitution occurring at the C9 position. The full single mass spectrum of alkaloids showed a strong signal for the protonated molecule [M+H]+. The product ion spectrum of mitragynine type of alkaloids showed strong response at m/z=174.0901 suggestive of an ion containing an odd number of nitrogen atoms corresponding to formula C11H12NO, which is characteristic of indole alkaloids. A multivariate statistical analysis technique, principal component analysis, was used to show discrimination between the M. speciosa samples. The results indicated that the analytical method is suitable for QC testing of various Mitragyna commercial samples and can be used to evaluate market products purported to contain M. speciosa.

ХИМИЧЕСКИЙ СОСТАВ ЭФИРНОГО МАСЛА HYSSOPUS OFFICINALIS L., КУЛЬТИВИРУЕМОГО В АСТРАХАНСКОЙ ОБЛАСТИ

By hydro distillation method were obtained samples of essential oils from Hyssopus officinalis L., cultivated in the Astrakhan region and the dependence of its yields from the plant vegetation period was studied. The highest yield of essential oil from flowers (0,6–0,8%) was observed. From the ground plant parts in the flowering stage essential oil was obtained in 0,4% yield of based on air-dry feed. Quantitative analysis of the components of essential oil of Hyssopus officinalis L. was performed by GLC method. From the 32 founded components in the essential oil were identified 27 compounds. Qualitative analysis was performed by comparing retention indices and linear full mass spectra data components with corresponding pure compounds. Quantification of components of essential oil was calculated from the gas chromatographic peak areas without correction factors. The main components of hyssop essential oil were oxygenated monoterpenes: isopinocamphone (63,55%) and pinanediol (9,45%). Comparative analysis of the experimental results and the literature data on the component composition of essential oils of hyssop growing in other countries shows a significant difference in the chemical composition of the obtained samples of Hyssop officinalis L. essential oil. They lack limonene, thujones, linalool, and β-pinene content is significantly less (1,58%) than in the essential oil of hyssop grown in Poland (6,14%) and India (18,4%).

A compact PTR-ToF-MS instrument for airborne measurements of volatile organic compounds at high spatiotemporal resolution

Abstract. Herein, we report on the development of a compact proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS) for airborne measurements of volatile organic compounds (VOCs). The new instrument resolves isobaric ions with a mass resolving power (m/Δm) of ~1000, provides accurate m/z measurements (Δm < 3 mDa), records full mass spectra at 1 Hz and thus overcomes some of the major analytical deficiencies of quadrupole-MS-based airborne instruments. 1 Hz detection limits for biogenic VOCs (isoprene, α total monoterpenes), aromatic VOCs (benzene, toluene, xylenes) and ketones (acetone, methyl ethyl ketone) range from 0.05 to 0.12 ppbV, making the instrument well-suited for fast measurements of abundant VOCs in the continental boundary layer. The instrument detects and quantifies VOCs in locally confined plumes (< 1 km), which improves our capability of characterizing emission sources and atmospheric processing within plumes. A deployment during the NASA 2013 DISCOVER-AQ mission generated high vertical- and horizontal-resolution in situ data of VOCs and ammonia for the validation of satellite retrievals and chemistry transport models.

Low-mass dilepton production with ALICE at the LHC

The production of low-mass dileptons, including those from ρ, ω and ϕ light vector meson decays, provides key information on the hot and dense state of strongly interacting matter produced in high-energy heavy-ion collisions. In particular, strangeness production can be studied through ϕ meson measurements, while the detailed description of the full dilepton mass spectra down to the kinematic threshold can be used to reveal in-medium modifications of hadron properties and the thermal emission arising from the medium. Measurements in pp and p–A, respectively, provide a reference for the observations in heavy-ion collisions and give insight on soft particle production in cold nuclear matter. Dilepton production is studied with the ALICE apparatus at the LHC both at central (|y|<0.9) and forward (2.5<y<4) rapidity, respectively in the dielectron and dimuon channel. In this contribution, we present recent results on low-mass dimuon production at forward rapidity in Pb–Pb and p–Pb collisions.

The Taurus Boundary of Stellar/Substellar (TBOSS) Survey

With Herschel/PACS 134 low mass members of the Taurus star-forming region spanning the M4-L0 spectral type range and covering the transition from low mass stars to brown dwarfs were observed. Combining the new Herschel results with other programs, a total of 150 of the 154 M4-L0 Taurus members members have observations with Herschel. Among the 150 targets, 70um flux densities were measured for 7 of the 7 ClassI objects, 48 of the 67 ClassII members, and 3 of the 76 ClassIII targets. For the detected ClassII objects, the median 70um flux density level declines with spectral type, however, the distribution of excess relative to central object flux density does not change across the stellar/substellar boundary in the M4-L0 range. Connecting the 70um TBOSS values with the results from K0-M3 ClassII members results in the first comprehensive census of far-IR emission across the full mass spectrum of the stellar and substellar population of a star-forming region, and the median flux density declines with spectral type in a trend analogous to the flux density decline expected for the central objects. SEDs were constructed for all TBOSS targets covering the optical to far-IR range and extending to the submm/mm for a subset of sources. Based on an initial exploration of the impact of different physical parameters; inclination, scale height and flaring have the largest influence on the PACS flux densities. From the 24um to 70um spectral index of the SEDs, 5 new candidate transition disks were identified. The steep 24um to 70um slope for a subset of 8 TBOSS targets may be an indication of truncated disks in these systems.Two examples of mixed pair systems that include secondaries with disks were measured. Finally, comparing the TBOSS results with a Herschel study of Ophiuchus brown dwarfs reveals a lower fraction of disks around the Taurus substellar population.

Evaluation of quadrupole-time-of-flight mass spectrometry in comprehensive two-dimensional gas chromatography

Quadrupole time-of-flight mass spectrometry (Q-TOFMS) has been evaluated with respect to its applicability in comprehensive two-dimensional gas chromatography (GC×GC). At a maximum acquisition frequency, while approximately 50 full accurate mass spectra on disk were acquired per s (50Hz) in scan mode, the sampling rate in target mode (MS/MS) was strongly dependent on the number of target ions selected. The number of selected precursor ions per time window proportionally decreased the acquisition rate for each ion; one precursor ion ≅31.35Hz; two ions ≅16.68Hz; and for 8 precursor ions, a sampling rate of just 4.18Hz was found. When Q-TOFMS was used in simultaneous mode, where in addition to the acquisition of target ion MS/MS signals, it also collects the full mass spectrum, sampling rates were even lower. It is demonstrated that Q-TOFMS generates sufficient data points over each peak in GC×GC operation in scan mode using TOFMS acquisition only, or is able to collect sufficient data points for relatively wide chromatographic peaks (≥600ms) in the target mode (MS/MS), however only if one or two precursor ions are selected per time window. Mass accuracy was found to perform within specification (<5ppm), even for the fastest acquisition operation (50Hz). Spectral deconvolution is demonstrated to work better in GC×GC than in 1D GC mode. Data visualisation in target GC×GC mode presents difficulties when there are overlapping target windows comprising different numbers of precursor ions.

Enhancing non-refractory aerosol apportionment from an urban industrial site through receptor modeling of complete high time-resolution aerosol mass spectra

Abstract. Receptor modeling was performed on quadrupole unit mass resolution aerosol mass spectrometer (Q-AMS) sub-micron particulate matter (PM) chemical speciation measurements from Windsor, Ontario, an industrial city situated across the Detroit River from Detroit, Michigan. Aerosol and trace gas measurements were collected on board Environment Canada's Canadian Regional and Urban Investigation System for Environmental Research (CRUISER) mobile laboratory. Positive matrix factorization (PMF) was performed on the AMS full particle-phase mass spectrum (PMFFull MS) encompassing both organic and inorganic components. This approach compared to the more common method of analyzing only the organic mass spectra (PMFOrg MS). PMF of the full mass spectrum revealed that variability in the non-refractory sub-micron aerosol concentration and composition was best explained by six factors: an amine-containing factor (Amine); an ammonium sulfate- and oxygenated organic aerosol-containing factor (Sulfate-OA); an ammonium nitrate- and oxygenated organic aerosol-containing factor (Nitrate-OA); an ammonium chloride-containing factor (Chloride); a hydrocarbon-like organic aerosol (HOA) factor; and a moderately oxygenated organic aerosol factor (OOA). PMF of the organic mass spectrum revealed three factors of similar composition to some of those revealed through PMFFull MS: Amine, HOA and OOA. Including both the inorganic and organic mass proved to be a beneficial approach to analyzing the unit mass resolution AMS data for several reasons. First, it provided a method for potentially calculating more accurate sub-micron PM mass concentrations, particularly when unusual factors are present, in this case the Amine factor. As this method does not rely on a priori knowledge of chemical species, it circumvents the need for any adjustments to the traditional AMS species fragmentation patterns to account for atypical species, and can thus lead to more complete factor profiles. It is expected that this method would be even more useful for HR–ToF–AMS data, due to the ability to understand better the chemical nature of atypical factors from high-resolution mass spectra. Second, utilizing PMF to extract factors containing inorganic species allowed for the determination of the extent of neutralization, which could have implications for aerosol parameterization. Third, subtler differences in organic aerosol components were resolved through the incorporation of inorganic mass into the PMF matrix. The additional temporal features provided by the inorganic aerosol components allowed for the resolution of more types of oxygenated organic aerosol than could be reliably resolved from PMF of organics alone. Comparison of findings from the PMFFull MS and PMFOrg MS methods showed that for the Windsor airshed, the PMFFull MS method enabled additional conclusions to be drawn in terms of aerosol sources and chemical processes. While performing PMFOrg MS can provide important distinctions between types of organic aerosol, it is shown that including inorganic species in the PMF analysis can permit further apportionment of organics for unit mass resolution AMS mass spectra.

Suspected-target pesticide screening using gas chromatography–quadrupole time-of-flight mass spectrometry with high resolution deconvolution and retention index/mass spectrum library

A strategy for suspected-target screening of pesticide residues in complicated matrices was exploited using gas chromatography in combination with hybrid quadrupole time-of-flight mass spectrometry (GC–QTOF MS). The screening workflow followed three key steps of, initial detection, preliminary identification, and final confirmation. The initial detection of components in a matrix was done by a high resolution mass spectrum deconvolution; the preliminary identification of suspected pesticides was based on a special retention index/mass spectrum (RI/MS) library that contained both the first-stage mass spectra (MS1 spectra) and retention indices; and the final confirmation was accomplished by accurate mass measurements of representative ions with their response ratios from the MS1 spectra or representative product ions from the second-stage mass spectra (MS2 spectra). To evaluate the applicability of the workflow in real samples, three matrices of apple, spinach, and scallion, each spiked with 165 test pesticides in a set of concentrations, were selected as the models. The results showed that the use of high-resolution TOF enabled effective extractions of spectra from noisy chromatograms, which was based on a narrow mass window (5mDa) and suspected-target compounds identified by the similarity match of deconvoluted full mass spectra and filtering of linear RIs. On average, over 74% of pesticides at 50ng/mL could be identified using deconvolution and the RI/MS library. Over 80% of pesticides at 5ng/mL or lower concentrations could be confirmed in each matrix using at least two representative ions with their response ratios from the MS1 spectra. In addition, the application of product ion spectra was capable of confirming suspected pesticides with specificity for some pesticides in complicated matrices. In conclusion, GC–QTOF MS combined with the RI/MS library seems to be one of the most efficient tools for the analysis of suspected-target pesticide residues in complicated matrices.

Remodeling of Marrow Hematopoietic Stem and Progenitor Cells by Non-self ST6Gal-1 Sialyltransferase

Glycans occupy the critical cell surface interface between hematopoietic cells and their marrow niches. Typically, glycosyltransferases reside within the intracellular secretory apparatus, and each cell autonomously generates its own cell surface glycans. In this study, we report an alternate pathway to generate cell surface glycans where remotely produced glycosyltransferases remodel surfaces of target cells and for which endogenous expression of the cognate enzymes is not required. Our data show that extracellular ST6Gal-1 sialyltransferase, originating mostly from the liver and released into circulation, targets marrow hematopoietic stem and progenitor cells (HSPCs) and mediates the formation of cell surface α2,6-linked sialic acids on HSPCs as assessed by binding to the specific lectins Sambucus nigra agglutinin and Polysporus squamosus lectin and confirmed by mass spectrometry. Marrow HSPCs, operationally defined as the Lin-c-Kit+ and Lin-Sca-1+c-Kit+ populations, express negligible endogenous ST6Gal-1. Animals with reduced circulatory ST6Gal-1 have marrow Lin-Sca-1+c-Kit+ cells with reduced S. nigra agglutinin reactivity. Bone marrow chimeras demonstrated that α2,6-sialylation of HSPCs is profoundly dependent on circulatory ST6Gal-1 status of the recipients and independent of the ability of HSPCs to express endogenous ST6Gal-1. Biologically, HSPC abundance in the marrow is inversely related to circulatory ST6Gal-1 status, and this relationship is recapitulated in the bone marrow chimeras. We propose that remotely produced, rather than the endogenously expressed, ST6Gal-1 is the principal modifier of HSPC glycans for α2,6-sialic acids. In so doing, liver-produced ST6Gal-1 may be a potent systemic regulator of hematopoiesis.

Investigation of the lipophilic constituents of Camphorosma lessingii

The genus Camphorosma (Chenopodiaceae) is represented by four species (C. lessingii, C. monspeliacum, C. annuum, and C. soongoricum) in salt marshes and rocky slopes of central and south Asia. Three species are indigenous to the flora of Kazakhstan (C. lessingii, C. monspeliacum, and C. soongoricum) [1–3]. The genus Camphorosma is used in folk medicine to treat various diseases such as lung diseases and rheumatism, and used in Central Asia externally to treat fungal skin diseases, and internally as a diuretic, diaphoretic, stimulant, and aphrodisiac [1, 2]. From this view point, it is definitely interesting as a raw material source for drug production.We studied previously the chemical composition of Campharosma monspeliacum L. [4, 5], and now we continue investigation of another species of the genus Campharosma not studied before. Because lipids affect the bioavailability and general pharmacotherapeutic effect of plant extracts and preparations based on them, and some of the biologically active compounds of plants are lipids that play an integral role in the metabolism of living organisms, our goal was to study the lipids of Camphorosma lessingii. We studied the chemical composition of lipids from the flowering parts of Camphorosma lessingii collected from the Almaty region in Kazakhstan. GC-MS analysis of the hexane extract of C. lessingii was performed by electron impact ionization (EI) (gas chromatography coupled with mass spectrometry) using a silica capillary column coated with PES [He carrier gas flow rate 1 mL/min, gradient column temperature 60–290 C, injector temperature 310oC, and ion source detector (EI-70 eV)]. The components were identified from the peak areas without using correction factors and by comparing their retention times and full mass spectra with the NIST and Wiley electronic libraries. GC-MS analysis revealed the presence of 12 known compounds comprising 32.31% of the total lipophilic constituents (Table 1). In addition to a number of unknown constituents, which represent about 67.69%, this high percent prompted us to do further comprehensive research on these lipophilic constituents.

Correlation Queries for Mass Spectrometry Imaging

Mass spectrometry imaging (MSI) generates large volumetric data sets consisting of mass to charge ratio (m/z), ion current, and x,y coordinate location. These data sets usually serve limited purposes centered on measuring the distribution of a small set of ions with known m/z. Such earmarked queries consider only a fraction of the full mass spectrum captured, and there are few tools to assist the exploration of the remaining volume of unknown data in terms of demonstrating similarity or discordance in tissue compartment distribution patterns. Here we present a novel, interactive approach to extract information from MSI data that relies on precalculated data structures to perform queries of large data sets with a typical laptop. We have devised methods to query the full volume to find new m/z values of potential interest based on similarity to biological structures or to the spatial distribution of known ions. We describe these query methods in detail and provide examples demonstrating the power of the methods to "discover" m/z values of ions that have such potentially interesting correlations. The "discovered" ions may be further correlated with either positional locations or the coincident distribution of other ions using successive queries. Finally, we show it is possible to gain insight to the fragmentation pattern of the parent molecule from such correlations. The ability to discover new ions of interest in the unknown bulk of an MSI data set offers the potential to further our understanding of biological and physiological processes related to health and disease.

Reliable Comparison of Electron Ionization Mass Spectra Recorded Under Identical Experimental Conditions

ABSTRACT For the most reliable identification by means of electron ionization mass spectrometry, the full mass spectra of unknown compound and possible candidate should be recorded under identical experimental conditions and compared. The main problem is how to compare full mass spectra, which may contain a lot of peaks. We have proposed a new approach (based on using principal component analysis) for the reliable comparison of electron ionization mass spectra recorded under identical experimental conditions. Applicability of the approach has been demonstrated on the example of xylenol isomers.

Combined use of liquid chromatography triple quadrupole mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry in systematic screening of pesticides and other contaminants in water samples

As a suitable way for routine screening of pesticides and control of other organic contaminants in water, the combination of liquid chromatography triple quadrupole tandem mass spectrometry (LC–QqQ-MS/MS) and liquid chromatography–hybrid quadrupole time-of-flight mass spectrometry (LC–QTOF-MS) has been applied to the analysis of 63 surface and waste water samples after conventional solid-phase extraction (SPE). The extracts were screened for 43 pesticides or degradation products by LC–QqQ-MS/MS achieving limits of detection (LOD) ranged from 0.04 to 2ngL−1. Of the 43 selected pesticides, 33 were detected in water samples. The ESI–QTOF MS instrument was run using two simultaneous acquisition functions with low and high collision energy (MSE approach) and acquiring the full mass spectra. A home-made database containing more than 1100 organic pollutants was used for substance identification. Around 250 of these compounds were available at the laboratory as reference standards. Five pesticides and 3 of their degradation products, different to those selected in the QqQ method, were detected by QqTOF-MS. Thirteen pharmaceuticals and two drugs of abuse were also identified in the samples. In practice, the sample preparation proved to be suitable for both techniques and for a wide variety of substances with different polarity. Mutual confirmation and evidence of co-occurrence of several other organic contaminants were the main advantages of the combination of both techniques.

Heavy Quarkonium Mass Spectra in A Coulomb Field Plus Quadratic Potential Using Nikiforov-Uvarov Method

In this work, the spin-averaged mass spectra of heavy quarkonia (cc and bb ) in a Coulomb plus quadratic potential is studied within the framework of nonrelativistic Schrodinger equation. The energy eigenvalues and eigenfunctions are obtained in compact forms for any -value using Nikiforov-Uvarov method. The obtained results are used to produce potential parameters (a, b , and o ) for the charmonium and bottomonium systems, from which then their full mass spectra are determined. The obtained values are compared with the available experimental results. The predictions from our model are found to be in good agreement with the experimental results. As a side result, the Hydrogen atom known spectrum is recovered.

Rapid detection and quantification of 35 benzodiazepines in urine by GC-TOF-MS

A rapid and sensitive method for the screening and quantification of 35 benzodiazepines in human urine by gas chromatography/time-of-flight mass spectrometry was developed and validated. Target analytes were isolated from 1 ml urine by solid-phase extraction using Oasis MCX extraction columns (extraction recovery between 35 and 99%). With a supported liquid-liquid extraction method, a new modification of conventional liquid-liquid-extraction, a less time intensive alternative for benzodiazepine extraction is presented. The sample pretreatment entails the derivatization of the benzodiazepines with N,O-bis(trimethylsilyl)trifluoroacetamide plus 1% trimethylchlorosilane. Separation of all benzodiazepines was done within 9.5 min, and detection was based on full mass spectra for each analyte. A deconvolution algorithm was used for unresolved chromatographic peaks to identify coeluted substances. The subsequent quantification was done using significant masses. The limit of quantification is 10 ng/ml for most of the compounds. Linearity is in the range between 10 and 350 ng/ml. Reproducibility was observed with coefficients of variation below 2% at concentrations of 50 and 200 ng/ml. The accuracy is between 88 and 108% depending on the respective analyte and the concentration.

Methoxy-substituted octachlorodibenzo-p-dioxins in the Vietnamese soil

A lot of data have been accumulated to date on the sources of formation of polychlorinated dibenzodiox� ins (PCDD) and dibenzofurans (PCDF), their envi� ronmental levels, and effects on living organisms, but there relatively few data about the properties of these compounds (1). Indeed, the octachlorodibenzop� dioxin (OCDD) phenomenon, in particular, the fact that it is detected in very high concentrations in soils that have not been affected by any human interven� tion, while the concentrations of other PCDD in these soils exponentially decrease and the PCDF level is negligibly low, has not been explained as yet. Often, this abnormal profile is detected in hot climate areas such as Australia, Thailand (2, 8), and Vietnam (4). Moreover, this compound is not characteristic of any industrial process. The source of OCDD in these areas is unknown but probably detection of some precursors or metabolites would help to estimate the theory of natural formation of OCDD from pentachlorophenol (PeCP), which was indirectly supported by our earlier study (5). Here, we present the results of detailed analysis of a soil sample with abnormally high OCDD concentra� tion collected at the Sa Pa mountain range in the North of Vietnam. Due to the low absolute concentra� tions of PCDD/PCDF, these compounds are deter� mined most efficiently by gas chromatography/high� resolution mass spectrometry (GC/HRMS) with recording of selected characteristic ions. Since the compounds to be determined were unknown before� hand, we applied GC/HRMS in the full scan mode, i.e., recorded the full highresolution mass spectrum. EXPERIMENTAL The soil and bottom sediment samples were taken in 2010 by expeditions organized by the Russian- Vietnam Tropical Center. The samples were analyzed at the Laboratory for Analytical Ecotoxicology of the Institute of Ecology. In all samples, PCDD, PCDF, and PeCP were determined by gas chromatogra� phy/highresolution mass spectrometry (GC/HRMS) with isotope dilution (4). The possible OCDD metab� olites were determined by recording GC/MS patterns in the full scan mode and the selected ion detection (SID) mode. The samples were extracted with a toluene-ace� tone mixture and with an aqueous solution of sodium hydroxide; this was followed by acidification of the aqueous phase and reextraction into dichloromethane. The extracts were analyzed without purification and after passing through a silica gel layer impregnated with sulfuric acid.

Virtual separation of phytochemical constituents by their adduct-ion patterns in full mass spectra

In the present study, a tool called classifier for traditional Chinese medicine (CTCM) was developed to facilitate the discrimination of phytochemical constituents in two-dimensional datasets of liquid chromatography/mass spectrometry (LC/MS). Based on the full mass spectral characteristics of components in a mixture, particularly their adduct-ion patterns, an entire LC/MS dataset can be separated into several sub-datasets, each corresponding to one or several types of natural products. CTCM has been verified using 24 standard compounds and successfully applied in two previously reported LC/MS datasets, which confirmed the capability of proposed tool to extract adduct-ion patterns from LC/MS datasets. Moreover, the LC/MS dataset of a Wei-Fu-Chun (WFC) tablet, a prescription drug consisting of three crude herbs used for the treatment of enteric diseases, was analyzed using CTCM. The analysis indicated that the compounds in WFC could be split into three groups, with the main constituents including saponins from Radix Ginseng Rubra, flavonoids from Fructus aurantii, and phenolic compounds from Isodon amethystoides. The major compounds in the three groups were either positively identified or tentatively characterized by multi-stage and high resolution MS. The proposed tool provides a novel approach for processing the LC/MS datasets of complex samples, such as traditional Chinese medicine and botanical drugs.

Serum Peptide Profiles of Duchenne Muscular Dystrophy (DMD) Patients Evaluated by Data Handling Strategies for High Resolution Content

The accuracy of Mass Spectrometry (MS)-based analysis of peptides in complex biological mixtures improves upon using high resolution instrumentation. However, high resolution content poses challenges to data processing and statistical analysis. Here, three different data handling strategies were evaluated with respect to classification performance using a well-defined cohort of serum samples from Duchenne Muscular Dystrophy (DMD) patients and controls. For this purpose, serum samples were purified using a solid-phase extraction (SPE) protocol based on Reversed-Phase (RP) C18 magnetic beads. Isotopically-resolved peptide profiles were acquired on a Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectrometer and examined by either using the full mass spectrum or after selecting peaks between 1000<m/z<4000 followed by data filtering or data integration. To identify discriminative peptides, linear Logistic Regression Analysis (LRA) with double-cross validation was applied for each method. The data integration strategy resulted in the lowest classification error rate while use of the filtered or full profile data gave higher error rates. From this it was concluded that peak selection methods may increase the discriminative power, however with the potential downside of loss of potentially interesting peptides. Seven peptides were found by all three methods when considering the top 15 discriminating peptides. Correlation analysis of discriminative peptides showed strong associations between peptides of different m/z-values, suggesting that the list of discriminative peptides reflected a smaller group of proteins. Validation studies using larger patient cohorts are required for further statistical evaluation of these results.

Direct monitoring of drug degradation by easy ambient sonic-spray ionization mass spectrometry: the case of enalapril

Using enalapril maleate as a test case, the ability of ambient mass spectrometry, namely, via easy ambient sonic-spray ionization mass spectrometry (EASI-MS), to perform direct monitoring of drug degradation has been tested. Two manufacturing processes were investigated (direct compression and wet granulation), and the formation of degradation products was measured via both EASI-MS and high-performance liquid chromatography with ultraviolet detection for a total period of 18 months. Both techniques provide comparable results, which indicate that direct analysis by ambient mass spectrometric techniques presents a viable alternative for drug degradation monitoring with superior simplicity, throughput, and reliability (no sample manipulation), and comparable quantitative results. In terms of qualitative monitoring, the full mass spectra with intact species provided by EASI-MS allow for comprehensive monitoring of known and unknown (or unexpected) degradation products.

Inlet Ionization: A New Highly Sensitive Approach for Liquid Chromatography/Mass Spectrometry of Small and Large Molecules

Inlet ionization is a new approach for ionizing both small and large molecules in solids or liquid solvents with high sensitivity. The utility of solvent based inlet ionization mass spectrometry (MS) as a method for analysis of volatile and nonvolatile compounds eluting from a liquid chromatography (LC) column is demonstrated. This new LC/MS approach uses reverse phase solvent systems common to electrospray ionization MS. The first LC/MS analyses using this novel approach produced sharp chromatographic peaks and good quality full mass range mass spectra for over 25 peptides from injection of only 1 pmol of a tryptic digest of bovine serum albumin using an eluent flow rate of 55 μL min(-1). Similarly, full acquisition LC/MS/MS of the MH(+) ion of the drug clozapine, using the same solvent flow rate, produced a signal-to-noise ratio of 54 for the major fragment ion with injection of only 1 μL of a 2 ppb solution. LC/MS results were acquired on two different manufacturer's mass spectrometers using a Waters Corporation NanoAcquity liquid chromatograph.