Specific Mass Spectrum Research Articles

Rapid Single Particle Atmospheric Solids Analysis Probe-Mass Spectrometry for Multimodal Analysis of Microplastics.

Despite mass spectrometry (MS) being proven powerful for the characterization of synthetic polymers, its potential for the analysis of single particle microplastics (MPs) is yet to be fully disclosed. To date, MPs are regarded as ubiquitous contaminants, but the limited availability of techniques that enable full characterizations of MPs results in a lack of systematic data regarding their occurrence. In this study, an atmospheric solid analysis probe (ASAP) coupled to a compact quadrupole MS is proposed for the chemical analysis of single particle microplastics, while maintaining full compatibility with complementary staining and image analysis approaches. A two-stage ASAP probe temperature program was optimized for the removal of additives and surface contaminants followed by the actual polymer characterization. The method showed specific mass spectra for a wide range of single particle MPs, including polyolefins, polyaromatics, polyacrylates, (bio)polyesters, polyamides, polycarbonates, and polyacrylonitriles. The single particle size detection limits for polystyrene MPs were found to be 30 and 5 μm in full scan and selected ion recording mode, respectively. Moreover, results are presented of a multimodal microplastic analysis approach in which filtered particles are first characterized by staining and fluorescence microscopy, followed by simple probe picking of individual particles for subsequent analysis by ASAP-MS. The method provides a full characterization of MP contamination, including particle number, particle size, particle shape, and chemical identity. The applicability of the developed multimodal method was successfully demonstrated by the analysis of MPs in bioplastic bottled water.

Primordial black holes and dark matter mass spectra

Abstract Because primordial black holes (PBHs) evaporate into all particle species in nature, PBHs may emit several dark matter (DM) particle species with specific mass spectra. We assume that PBHs are the only source of DMs, and DMs only interact with the standard model particles gravitationally. We show a relation between the number of DM particle species NDM and initial PBH density β and mass $M_{\rm BH}^{\rm in}$. β–$M_{\rm BH}^{\rm in}$ curves for different NDM tend to overlap with each other for heavy initial PBHs. We also show the allowed region of DM masses for multiple DMs.

Dark matter and lepton flavour phenomenology in a singlet-doublet scotogenic model

We study the dark matter phenomenology of scotogenic frameworks through a rather illustrative model extending the Standard Model by scalar and fermionic singlets and doublets. Such a setup is phenomenologically attractive since it provides the radiative generation of neutrino masses, while also including viable candidates for cold dark matter. We employ a Markov Chain Monte Carlo algorithm to explore the associated parameter space in view of numerous constraints stemming from the Higgs mass, the neutrino sector, dark matter, and lepton-flavour violating processes. After a general discussion of the results, we focus on the case of fermionic dark matter, which remains rather uncovered in the literature so far. We discuss the associated phenomenology and show that in this particular case a rather specific mass spectrum is expected with fermion masses just above 1 TeV. Our study may serve as a guideline for future collider studies.

Detection of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in blood in a forensic case using liquid chromatography–electrospray ionization linear ion trap mass spectrometry

We present a case of fatal poisoning by 4-F-methcathinone (4-FMC; also called flephedrone), 4-methoxy-α-pyrrolidinopentiophenone (4-MeO-α-PVP), 4-fluoro-α-pyrrolidinopentiophenone (4-F-α-PVP), and α-pyrrolidinohepatanophenone (PV8). In this study, we compared the mass spectra of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, PV8, and α-pyrrolidinohexanophenone between LC–ESI–LIT–MS and GC–EI–MS analyses. Subsequently, we applied LC–ESI–LIT–MS for detection and quantification analyses of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in human authentic whole blood samples. More specific mass spectra for the target compounds were obtained with the LC–ESI–LIT–MS qualitative analyses than with the GC–EI–MS analyses, indicating that LC–ESI–LIT–MS was more suitable for the qualitative analysis of cathinones. The LC–ESI–LIT–MS validation data showed moderately good linearity and reproducibility for the compounds in the quantitative analyses at the range of 1–500 ng/mL. The detection limits of four cathinones ranged from 0.1 to 1 ng/mL. The concentrations of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in heart whole blood samples were 365, 449, 145, and 218 ng/mL, respectively. Those of the 4 cathinones in femoral vein whole blood samples were 397, 383, 127, and 167 ng/mL, respectively. We can then assume that the cause of death was acute poisoning by a combination of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8. In this article, we present a detailed LC–ESI–LIT–MS procedure for detection and quantification analyses of 4-FMC, 4-MeO-α-PVP, 4-F-α-PVP, and PV8 in authentic human whole blood samples.

Replacing the internal standard to estimate micropollutants using deep and machine learning

Similar to the worldwide proliferation of urbanization, micropollutants have been involved in aquatic and ecological environmental systems. These pollutants have the propensity to wreak havoc on human health and the ecological system; hence, it is important to persistently monitor micropollutants in the environment. Micropollutants are commonly quantified via target analysis using high resolution mass spectrometry and the stable isotope labeled (SIL) standard. However, the cost-intensiveness of this standard presents a major obstacle in measuring micropollutants. This study resolved this problem by developing data-driven models, including deep learning (DL) and machine learning (ML), to estimate the concentration of micropollutants without resorting to the SIL standard. Our study hypothesized that natural organic matter (NOM) could replace internal standards if there was a specific mass spectrum (MS) subset, including NOM information, which correlated with an SIL standard peak. Therefore, we analyzed the MS to find the specific MS subsets for replacing the SIL standard peak. Thirty-five alternative MS subsets were determined for applying DL and ML as input data. Thereafter, we trained four different DL models, namely, ResNet101, GoogLeNet, VGG16, and Inception v3, as well as three different ML models, i.e., random forest (RF), support vector machine (SVM), and artificial neural network (ANN). A total of 680 MS data were used for the model training to estimate five different micropollutants, namely Sulpiride, Metformin, and Benzotriazole. Among the DL models, ResNet 101 exhibited the highest model performance, showing that the average validation R2 and MSE were 0.84 and 0.26 ng/L, respectively, while RF was the best in the ML models, manifesting R2 and MSE values of 0.69 and 0.58 ng/L. The trained models showed accurate training and validation results for the estimation of the five micropollutant concentrations. Therefore, this study demonstrates that the suggested analysis has a potential for alternative micropollutant measurement that has rapid and economic vantages.

Determination of sildenafil citrate adulterated in a dietary supplement capsule by LC/MS/MS

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was used to identify and quantify an adulterated substance, in a dietary supplement capsule. The capsule is claimed to be an extract of animal organs and traditional Chinese herbs and indicated for enhancing sexual activity. At first, the sample was extracted with 50% v/v methanol in water and the extract was injected directly into the LC/MS/MS with no separation and a full scan of positive ion eletrospray (ESI +) analysis was performed. The full scan mass spectrum was compared with the NLFD3/LM library created by Division 3rd of National Laboratories of Foods and Drugs for LC/MS/MS analysis. A sildenafil specific mass spectrum was matched indicating that the capsule may have been adulterated with sildenafil, the active ingredient of VIAGRA®. Furthermore, sildenafil was confirmed by carrying out a daughter ion scan and a parent ion scan. The daughter ion spectrum was compared with the NLFD3/LM library. A negative ion eletrospray (ESI -) analysis was performed for confirming the citrate salt in the capsule. The results indicated that the adulterated ingredient was sildenafil citrate. For quantitative analysis of the sildenafil citrate, multiple reaction monitoring (MRM) was performed. Pirenzepine 2HCL was used as the internal standard. A series of standards solution and sample solution with internal standard were analyzed by LC/ MS/MS. The analytical condition is as following: column: Cosmosil 5C18-AR, 4.6 x 150 mm; mobile phase:methanol:acetonitrile: 1% acetic acid (25:17:58); capillary voltage: 3 kV;cone voltage: 80 V; collision energy: 25 eV; source temperature: 120°C; desolvation temperature: 350°C. The detection limit was 40 ng/mL. An excellent calibration curve of sildenafil citrate was obtained with the γ 2 correlation coefficient of 0.9977. The RSDs of interday and intraday were between 7.56∼7.75% and 9.09∼11.25%, respectively. The analytical strategy and method is suitable for identification and measurement of sildenafil citrate adulterated in capsule. Amount of sildenafil citrate in the capsule was determined as 42.8 mg/capsule.

Primordial black holes from sound speed resonance in the inflaton-curvaton mixed scenario

We study sound speed resonance (SSR) mechanism for primordial black hole (PBH) formation in an early universe scenario with inflaton and curvaton being mixed. In this scenario, the total primordial density perturbations could be contributed by the fluctuations from both the inflaton and curvaton fields, in which the inflaton fluctuations lead to the standard adiabatic perturbations, while the sound speed of the curvaton fluctuations are assumed to be oscillating during inflation. Due to the narrow resonance effect of SSR mechanism, we acquire the enhanced primordial density perturbations on small scales and they remain nearly scale-invariant on large scales, which is essential for PBH formation. Finally, we find that the PBHs with specific mass spectrum can be produced with a sufficient abundance for dark matter in the mixed scenario.

Capillary zone electrophoresis-native mass spectrometry for the quality control of intact therapeutic monoclonal antibodies

Therapeutic monoclonal antibodies (mAbs) are complex glycoproteins and ensuring their safety, efficacy and quality is still challenging. Indeed, during their manufacturing process, they are exposed to several stresses that can lead to their denaturation, misfolding or dimerization. We report here a new method based on capillary electrophoresis coupled to native mass spectrometry (MS) with a sheath liquid interface to analyze an intact therapeutic mAb, Infliximab, under non-denaturing conditions that preserve its conformational heterogeneity as well as self-association without inducing further unfolding / denaturation. For capillary zone electrophoresis (CZE) separation, a triple layer coating using polybrene-dextran sulfate-polybrene was employed. A sheath liquid composed of isopropanol - water - acetic acid with a flow rate of 10 μL min−1 and mild MS conditions allowed optimal signal intensities. A specific mass spectrum was obtained for each Infliximab conformation in a “stressed” formulated preparation. This is the first time that within a single analysis different conformational states, i.e. native and unfolded monomers as well as dimers are simultaneously detected. The results and the lack of analytical bias arising from the CZE-MS conditions were confirmed by using atomic force microscopy (AFM) as an orthogonal technique. A middle-up approach combined to CZE-MS analysis of the stressed samples suggested that the dimer formation involved mostly Fab-Fab interactions.

Direct identification of edible insects by MALDI-TOF mass spectrometry

The consumption of edible insects (entomophagy) will gain greater significance facing the increasing global population, which is suggested to reach 9 billion people in 2050 (FAO., 2009). Due to their high amount of proteins, fatty acids, vitamins, and minerals insects represent a valuable source of essential nutrients.While the consumption of insects is very common in many countries of Africa and Asia, there is a far smaller acceptance for entomophagy in Western cultures. Though, products such as noodles or burger paddies made from insect meal have a better compliance and can already be purchased in some countries of the European Union. This processing step however involves the risk of adulteration, because there is no more possibility to authenticate the insects once they are ground.The aim of this study was to investigate whether edible insects could be measured and distinguished by MALDI-TOF MS (matrix-assisted laser desorption ionization-time of flight mass spectrometry). Therefore, different kinds of edible insects (buffalo worms, mealworms, crickets and grasshoppers) were purchased via online shops and ground subsequently. The insect powder was extracted by vigorously shaking in diluted formic acid and measured by MALDI-TOF MS. The measurement provided reproducible as well as specific mass spectra and enabled a precise differentiation of the different species.

Characterization of conformers and dimers of antithrombin by capillary electrophoresis-quadrupole-time-of-flight mass spectrometry

Antithrombin (AT) is a plasma glycoprotein which possesses anticoagulant and anti-inflammatory properties. AT exhibits various forms, among which are native, latent and heterodimeric ones. We studied the potential of capillary electrophoresis-mass spectrometry (CE-MS) using a sheath liquid interface, electrospray ionization (ESI), and a quadrupole-time-of-flight (Q-TOF) mass spectrometer to separate and quantify the different AT forms. For CE separation, a neutral polyvinyl alcohol (PVA) coated capillary was employed. The protein conformation was preserved by using a background electrolyte (BGE) at physiological pH. A sheath liquid of isopropanol-water 50:50 (v/v) with 14 mM ammonium acetate delivered at a flow rate of 120 μL h−1 resulted in optimal signal intensities. Each AT form exhibited a specific mass spectrum, allowing unambiguous distinction. Several co-injection experiments proved that latent AT had a higher electrophoretic mobility (μep) than native AT, and that these conformers could associate to form a heterodimer during the CE analysis. The developed CE-MS method enabled the detection and quantitation of latent and heterodimeric forms in a commercial AT preparation stored at room temperature for three weeks.

Black Component of Dark Matter

A mechanism of primordial black hole formation with specific mass spectrum is discussed. It is shown that these black holes could contribute to the energy density of dark matter. Our approach is elaborated in the framework of universal extra dimensions.

Paracetamol Interference in Uric Acid Levels in Uremic Patients Revealed by Monitoring Spent Dialysate

The aim of this study was to assess removal dynamics of paracetamol (PAR), as an extraordinary chromophore in spent dialysate, upon the optical monitoring of dialysis of end-stage renal disease patients with inflammation complications. Seven dialysis sessions of different patients were followed to whom PAR was used as a pain reliever or antipyretic. Spent dialysate was sampled hourly and analyzed using HPLC with MS/MS and UV detection. Quantitative calculations were made on the basis of the peak areas on the chromatograms at 280 nm for uric acid (UA) and 254 nm for PAR and its metabolites (PAR-M). Peaks of UA, PAR, PAR-glucuronide, and PAR-sulphate were identified on the basis of specific mass spectra. Removal of PAR was found to be proportional to that of uric acid if intake of the drug by patient occurred half a day before dialysis. But disturbances of the UV-absorbance curves at 280 nm were observed related to rise of UA concentration in spent dialysate when PAR was taken by patients in the course of dialysis. The mechanism of such relation remains unknown. It was concluded that possible benefits and risks of treatment of uremic patients with paracetamol-containing drugs may need to be reassessed.

Higgs inflation in a radiative seesaw model

We investigate a simple model to explain inflation, neutrino masses and dark matter simultaneously. This is based on the so-called radiative seesaw model proposed by E. Ma in order to explain neutrino masses and dark matter by introducing a Z2-odd isospin doublet scalar field and Z2-odd right-handed neutrinos. We study the possibility that the Higgs boson as well as neutral components of the Z2-odd scalar doublet field can satisfy conditions from slow-roll inflation and vacuum stability up to the inflation scale. We find that a part of parameter regions where these scalar fields can play a role of an inflaton is compatible with the current data from neutrino experiments and those of the dark matter abundance as well as the direct search results. A phenomenological consequence of this scenario results in a specific mass spectrum of scalar bosons, which can be tested at the LHC, the International Linear Collider and the Compact Linear Collider.

Ambient Mass Spectrometry for the Intraoperative Molecular Diagnosis of Human Brain Tumors

The role of surgery in the management of brain tumors is a delicate balancing act in which the surgeon's goal is to maximize tumor resection while minimizing postoperative neurological deficits. Surgery for gliomas is challenging because of the infiltrative nature of these lesions. Delineation of surgical margins is especially difficult, as the periphery of the tumor becomes indistinguishable from the surrounding normal brain. Neurosurgeons utilize a variety of tools in order to address this problem such as intraoperative MRI, fluorescence labeling, and intraoperative histopathological analysis.1-3 At present, histopathological examination with immunohistochemistry labeling, genetic and proteonomic analysis are collectively considered the gold standards for diagnosis and classification of tumors. However, the lengthy processing time required for these results makes them impractical tools to help guide intraoperative decision making in order to achieve maximal tumor resection. Recent research published in Proceedings of the National Academy of Science from Purdue University and Brigham and Women's Hospital, demonstrates a novel method to provide accurate intraoperative tumor diagnosis as well as sample composition in near-real time using desorption electrospray ionization mass spectrometry (DESI-MS).4 The technique is performed by direct lipid analysis from tumor samples and takes less than a second to provide the result. The group's initial experiments demonstrated that the DESI-MS technique could distinguish between the lipid profiles of gliomas vs meningiomas. Using 21 banked glioma samples and 11 banked meningioma samples, the group was able to train a computerized classification model to detect the unique lipid profiles of these two tumor types.5 The accuracy of this prediction model was subsequently validated on a second set of 15 gliomas and 8 meningiomas with a 100% agreement between the lipid profile analysis and the histological diagnosis.6 The researchers then applied the DESI-MS technique to tissue samples from 5 stereotactic surgical cases. Tissue samples were registered from MRI images used for image guidance and analyzed ex situ using DESI-MS. The results of the DESI-MS analysis were then correlated to the histopathological analysis. In one of the representative surgical cases (Case 2) seven surgical samples were obtained and analyzed (S7, S8, S10-S13, and S15) by DESI-MS. DESI mass spectra revealed lipid profiles that were characteristic of a low-grade glioma. Changes in the relative abundances of ions due to certain lipid species are observed as a function of grade for oligodendrogliomas. For example, the ratio between specific mass spectra peaks increases as the grade of the oligodendroglioma increases. When tested for glioma subtype, grade, and tumor cell concentration, agreement was achieved for all samples within all classes when compared to the histological analysis (Table 1). Some anticipated disparity in the DESI-MS and histological analysis was seen mostly in distinguishing between tumor grades II & III. The group justifies these differences based on the inherent heterogeneity of tumor cells especially seen at the margins of the tumor, where neoplastic cells are admixed with normal surrounding brain tissue. Additional testing was performed on 4 other surgical specimens with similar results in which the DESI-MS analysis correlated to histological observations with high fidelity. In conclusion, DESI-MS is a near-real time intraoperative tumor-analyzing tool that permits rapid, reliable, and reproducible results with regard to tumor type, subtype, grade and concentration. Such information may prove to be invaluable in guiding the neurosurgeon to achieve maximal tumor resection while minimizing the extent of collateral damage to the surrounding normal brain tissue. Although currently at its infancy, the implications of this novel technique are far reaching and hold promise in helping surgeon and patient alike in the treatment of these challenging tumors.Figure: A representative DESI-MS mass spectra obtained from a surgical Sample. The lipid profile observed is highly characteristic of oligodendroglioma. Reprinted with Permssion from: Eberlina LS, Norton I, Orringer D, et al. Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors. Proc Natl Acad Sci U S A. 2013;110(5):1611-1616.

Laser desorption/ionization of carbon clusters

Results of mass spectrometric investigations of soot by using the laser desorption/ionization (LDI) method and time of flight (TOF) mass spectrometry are presented. Several liquid fuels (benzene, tetrahydrofuran, toluene, acetonitrile, acetone, isopropanol, ethanol) were used to produce soot samples. Each soot gives specific mass spectrum of carbon clusters C n as well as their size. The best clustering process was observed for benzene soot with the cluster size n⩽31. The benzene soot was applied in the detection of insulin by using the matrix-assisted laser desorption/ionization (MALDI) method.

Link test—A statistical method for finding prostate cancer biomarkers

We present a new method, link- test, to select prostate cancer biomarkers from SELDI mass spectrometry and microarray data sets. Biomarkers selected by link-test are supported by data sets from both mRNA and protein levels, and therefore results in improved robustness. Link-test determines the level of significance of the association between a microarray marker and a specific mass spectrum marker by constructing background mass spectra distributions estimated by all human protein sequences in the SWISS-PROT database. The data set consist of both microarray and mass spectrometry data from prostate cancer patients and healthy controls. A list of statistically justified prostate cancer biomarkers is reported by link-test. Cross-validation results show high prediction accuracy using the identified biomarker panel. We also employ a text-mining approach with OMIM database to validate the cancer biomarkers. The study with link-test represents one of the first cross-platform studies of cancer biomarkers.

Bis‐methylene‐interrupted octadecadienoic fatty acids in Bulgarian bovine butter fats

AbstractPreparative silver nitrate thin‐layer chromatography of fatty acid methyl esters and gas chromatography‐mass spectrometry of 4,4‐dimethyloxazoline derivatives were applied in combination to analyze the cis,cis octadecadienoic (18:2) fraction in commercial samples of bovine butter fat in Bulgaria. The main component, 9,12–18:2 was accompanied by a series of bis‐methylene‐interrupted isomers, cis,cis‐5,9‐; 6,10‐; 9,13‐ and 11,15–18:2, which were unambiguously identified by their specific mass spectra. The latter are characterized by the presence of very intensive diagnostic fragments which help to correctly locate the position of the double bond system in the carbon chain. The cis,cis‐5,9–18:2 isomer was found for the first time in butter fat, and the 6,10–18:2 isomer has not been described as yet.

Quaternion family symmetry of quarks and leptons

To a first approximation, the quark mixing matrix has $\theta^q_{13} = \theta^q_{23} = 0$, whereas the lepton mixing matrix has $\theta^l_{23} = \pi/4$. We show how this structure may be understood if the family symmetry is $Q_8$, the quaternion group of eight elements. We find three viable scenarios for the Majorana neutrino mass matrix, each depending on 4 parameters and predicting a specific mass spectrum. The phenomenology of the two Higgs doublets which generate the Yukawa sector is analyzed and testable predictions are derived. We discuss also the closely related model based on $D_4$, the symmetry group of the square.

Gas chromatographic–mass spectrometric analysis of di(2-ethylhexyl) phthalate and its metabolites in hepatic microsomal incubations

A method is reported for the determination of di(2-ethylhexyl) phthalate (DEHP) and its metabolites in in vitro metabolism studies. Gas chromatography–mass spectrometry (GC–MS) analysis allows separation of 18 by-products of DEHP metabolism. On the basis of retention time and specific mass spectra m/ z values, three classes of compounds can be identified: (i) alcohols as hydrolysis product; (ii) acids produced by alcohol oxidation; (iii) compounds retaining phthalic moiety. The chromatogram can also be acquired in SIM mode at m/ z 149 resulting in 13 well-separated chromatographic peaks: from retention time and mass spectra it can be inferred that the main peaks correspond to mono(2-ethylhexyl) phthalate (MEHP) and (ω-1)-hydroxyl-MEHP. The kinetics of DEHP metabolism was studied using an S9 Aroclor-induced liver fraction as in vitro model and following incubation assay after 20, 40, 60 and 90 min. The composition of incubation mixtures can be quantitatively evaluated from selected ion monitoring chromatograms at m/ z 149: the by-product concentration increases during the incubation time, as a consequence of DEHP degradation. During the incubation test a significant conversion of DEHP into MEHP is observed: a conversion yield of 10, 13, 16 and 20% of the original DEHP is obtained after 20, 40, 60 and 90 min, respectively. The metabolic conversion of DEHP to MEHP explains the endocrine-disrupting activity of the original DEHP; moreover, it has been demonstrated that MEHP and its (ω-1)-oxidation metabolite induce peroxisome proliferation. This result strengthens the suggestion that the study of DEHP metabolic pathway is fundamental to better understanding its toxicological behavior.

N-methyl-N-alkylsilyltrifluoroacetamide-I2 as a new derivatization reagent for anabolic steroid control.

Analytical methods for the control of growth promoters have to be specific and sensitive. At low concentration levels, it is difficult to identify some molecules unambiguously even with the improved performance of analytical methods. GC-MS analysis of 17 beta-trenbolone and its major metabolite, 17 alpha-trenbolone, is a good example. A new derivatization agent has been developed which is based on silylation of the 3- and 17-oxygenated functions and nucleophilic substitution in the 4-position. The structure of the derivatized products was demonstrated using a simple model, cyclohex-2-en-1-one, by NMR and MS spectrometry. In contrast to data found in the literature, this derivative permitted specific mass spectra for trenbolone, sensitive signals for high mass ions and reproducible gas chromatograms to be obtained. The addition of an N(CH3)COCF3 radical to the steroid nucles allowed highly specific detection in GC-high resolution MS even following extraction from complex matrices; sensitive responses were also observed in the negative chemical ionization mode. Moreover, there are significant differences in the electron ionization mass spectra of the two stereoisomers, 17 alpha- and 17 beta-trenbolone. These preliminary results and those obtained for androsta-1,4-dien-3-one and pregna-4,6-dien-3-one indicate useful advances for the determination of steroids and potential applications for metabolism studies on such compounds.