Direct Mass Spectrometry Method Research Articles

Direct mass spectrometry analysis of exhaled human breath in real-time.

The molecular composition of exhaled human breath can reflect various physiological and pathological conditions. Considerable progress has been achieved over the past decade in real-time analysis of exhaled human breath using direct mass spectrometry methods, including selected ion flow tube mass spectrometry, proton transfer reaction mass spectrometry, extractive electrospray ionization mass spectrometry, secondary electrospray ionization mass spectrometry, acetone-assisted negative photoionization mass spectrometry, atmospheric pressure photoionization mass spectrometry, and low-pressure photoionization mass spectrometry. Here, recent developments in direct mass spectrometry analysis of exhaled human breath are reviewed with regard to analytical performance (chemical sensitivity, selectivity, quantitative capabilities) and applications of the developed methods in disease diagnosis, targeted molecular detection, and real-time metabolic monitoring.

A direct mass spectrometry method for cannabinoid quantitation in urine and oral fluid utilizing reactive paper spray ionization.

A direct mass spectrometry method utilizing reactive paper spray ionization was developed for sensitive cannabinoid quantitation in biofluid matrices. The ca. 2-minute sample measurements used on-paper derivatization to significantly increase paper spray mass spectrometry (PS-MS) positive ion mode sensitivity while minimizing sample preparation steps. Calibrations demonstrate high linearity, with R2 > 0.99 for (-)-trans-Δ9-tetrahydrocannabinol (THC) in oral fluid and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine. The limit of detection and lower limit of quantitation were 0.78 and 10 ng mL-1 for THC in oral fluid and 1.3 and 10 ng mL-1 for THC-COOH in urine, respectively. THC-COOH levels measured by reactive PS-MS in seven spiked human urine samples showed bias of -9.4 to 5.9%, and percent difference values of -16.8 to 9.8% in comparison with a reference LC-MS method. Based upon the method simplicity, validation experiments, sensitivity, and rapidity, we conclude that reactive PS-MS has potential applications for rapid cannabinoid drug testing in urine and oral fluid.

Standard Validation Protocol for Selected Ion Flow Tube Mass Spectrometry Methods Applied to Direct Headspace Analysis of Aqueous Volatile Organic Compounds.

Analysis of volatile organic compounds (VOCs) in water is conventionally conducted using gas chromatography (GC)-based methods, for which sample preparation demands are relatively high and throughput is relatively low due to the time taken to achieve chromatographic separation. Direct mass spectrometry (DMS) techniques such as selected ion flow tube mass spectrometry (SIFT-MS) have potential to analyze water headspace (HS) at high sensitivity with minimal sample preparation, eliminating preconcentration/purging and/or water management steps. However, the dearth of guidance for validation of DMS methods is an impediment to their adoption in routine analysis. This study applies and adapts an internationally recognized pharmaceutical industry guidance document for method validation to a prototypical SIFT-MS headspace analysis method for 17 toxic VOCs in water. The approach to validation is, however, applicable to any routine analysis conducted using SIFT-MS, and very likely to any methods developed using other DMS techniques. For the method developed and validated here, linearities (as measured by the linear regression coefficient, R2) were better than 0.990 for all compounds. Repeatability (measured using relative standard deviation, RSD) was less than 10% for all compounds. Similar method performance was observed for accuracy and recovery. The performance criteria achieved by this HS-SIFT-MS method suggest it has potential application in environmental and pharmaceutical routine analyses, perhaps as a rapid screening tool.

РАЗРАБОТКА МЕТОДА ИСПОЛЬЗОВАНИЯ ПОРИСТЫХ ОБЪЕМНЫХ ПРОБООТБОРНИКОВ ДЛЯ ПРЯМОГО МАСС-СПЕКТРОМЕТРИЧЕСКОГО АНАЛИЗА БИОЛОГИЧЕСКИХ ОБРАЗЦОВ

The paper presents a method for rapid multi-omics investigation of biological samples using polypropylene bulk porous samplers. The use of porous samplers makes it easy to collect samples from the surface of the skin, mucous membranes, and biological fluids even in a field, and the surfaces of wounds and injuries. Collected samples do not require special storage conditions, and the samplers are lightweight and very compact. They can be used to monitor the condition of cosmonauts before, during, and after the spaceflight with the same sample collection method. The analysis of biomaterial applied to the sampler is performed using direct mass spectrometry methods, similar to the dried blood spot technique that is already used in clinical practice. However, bulk porous samplers allow expanding the range of analytes ionization conditions, which increases the stability and reliability of the ionization process, which expands the variety of analyzed molecules. The proposed method can be used to study compounds of various classes, including proteins, lipids, and metabolites, to systematically monitor the status of people in extreme conditions (athletes, astronauts), or to study the condition of patients in the clinic.

Novel Mass Spectrometric Utilities for Assisting in Oncological Surgery

Broad application of mass spectrometry in clinical practice was only possible with the development of the physicochemical fundamentals of the method. New ionization techniques and ion detection systems have not only enhance the variety of biomolecules in diagnostics, but also provided an opportunity to apply direct mass spectrometry methods to guide surgical interventions. Here we present a brief review of the latest achievements in mass spectrometry applications in oncological surgery and neurosurgery in particular. We describe our recent advance in this area and demonstrate that the combination of different mass spectrometric techniques improves the overall comprehensiveness of the analysis.

Condensed Phase Membrane Introduction Mass Spectrometry with In Situ Liquid Reagent Chemical Ionization in a Liquid Electron Ionization Source (CP-MIMS-LEI/CI)

Direct mass spectrometry has grown significantly due to wide applicability, relative ease of use, and high sample throughput. However, many current direct mass spectrometry methods are largely based on ambient ionization techniques that can suffer from matrix effects and poor selectivity. A strategy that addresses these shortcomings is condensed phase membrane introduction mass spectrometry-liquid electron ionization utilizing in situ liquid reagent chemical ionization (CP-MIMS-LEI/CI). In CP-MIMS measurements, a semipermeable hollow fiber polydimethylsiloxane membrane probe is directly immersed into a complex sample. Neutral, hydrophobic analytes permeating the membrane are entrained by a continuously flowing liquid acceptor phase (nL/min) to an LEI/CI source, where the liquid is nebulized, followed by analyte vaporization and ionization. This study marks the first intentional exploitation of the liquid CP-MIMS acceptor phase as an in situ means of providing liquid chemical ionization (CI) reagents for improved analyte sensitivity and selectivity (CP-MIMS-LEI/CI). Acetonitrile and diethyl ether were used as a combination acceptor phase/CI proton transfer reagent system for the direct analysis of dialkyl phthalates. Using isotopically labeled reagents, the gas phase ionization mechanism was found to involve reagent autoprotonation, followed by proton transfer to dialkyl phthalates. A demonstration of the applicability of CP-MIMS-LEI/CI for rapid and sensitive screening of bis(2-ethylhexyl) phthalate in house dust samples is presented. The detection limit in house dust (6 mg/kg) is comparable to that obtained by conventional analyses, but without time-consuming sample workup or chromatographic separation steps.

The analysis of the Saltzman Collection of Peruvian dyes by high performance liquid chromatography and ambient ionisation mass spectrometry

Yarn samples from the Saltzman Collection of Peruvian dyes were characterized by several different analytical techniques: high performance liquid chromatography with both diode array detection (HPLC-DAD) and electrospray ionisation with tandem mass spectrometry (HPLC-ESI-Q-ToF), direct analysis in real time (DART) mass spectrometry and paper spray mass spectrometry. This report serves primarily as a database of chemical information about the colorants in these dye materials for those studying ancient South American textiles and their colorants. We also provide a comparison of the results obtained by currently widespread HPLC techniques with those of two different ambient ionisation direct mass spectrometry methods to highlight the advantages and disadvantages of these approaches.

Risk factors for recurrence of external genital endometriosis after surgical treatment: prospective cohortant study

Objectives of the study: improve early non-invasive diagnosis of external genital endometriosis (EGE) using the mass spectrometry method, and determine the risk factors for recurrence of EGE after surgical treatment. Material and methods: a prospective cohort study included 100 patients with EGE who underwent surgical treatment during the 2014 to 2016 period. The EGE diagnosis was made on the basis of diagnostic and therapeutic laparoscopic findings and finally confirmed at histological exam. All patients underwent blood sampling before and after surgical treatment to detect recurrence of endometriosis using direct mass spectrometry method. Results: recurrences of EGE were diagnosed in 22% of patients at 18–36 months postoperatively. High incidence of recurrent EGE was reported in the group of patients who did not receive post-surgical hormonal therapy. The hormone therapy with dienogest 2 mg for 6-9 months, as well as with goserelin 3.6 mg for 3-6 months showed the greatest efficacy for the prevention of recurrent EGE. Significant predictive factors of recurrence after surgical treatment for EGE include intensive acyclic pelvic pain; presence of surgical interventions for the history of EGE; infertility; stimulation of ovulation with hormonal drugs as part of the Assisted Reproductive Technologies Program; degree 3-4 disease spread; pronounced adhesions of the small pelvis; infiltrative forms of endometriosis; endometrioid cysts of large size; bilateral ovarian lesions. The plasma lipid profile including determination of phosphatidylcholines, phosphoethanolamines, diglyceride and sphingomyelin in the patients with endometriosis provides an approach for noninvasive early diagnosis of recurrence of this disease by mass spectrometry (sensitivity 93%, specificity 95%). Conclusion: This study developed an individual comprehensive approach to the prevention of recurrent EGE, including surgical treatment, hormonal therapy and diagnosis of the disease at an early stage of development. Timely administration of a-GnRH or dienogest 2 mg at the post-surgery stage is associated with a minimal or total absence of recurrent EGE. The administration of COCs showed no efficacy in preventing the recurrence of EGE, and therefore COCs cannot be recommended as a prophylactic drug, but exclusively for contraceptive use.

Distinguishing Sulfotyrosine Containing Peptides from their Phosphotyrosine Counterparts Using Mass Spectrometry.

Sulfotyrosine and phosphotyrosine are two post-translational modifications present in higher eukaryotes. A simple and direct mass spectrometry method to distinguish between these modifications is crucial to advance our understanding of the sulfoproteome. While sulfation and phosphorylation are nominally isobaric, the accurate mass of the sulfuryl moiety is 9.6 mDa less than the phosphoryl moiety. Based on this difference, we have used an Orbitrap Fusion Lumos mass spectrometer to characterize, resolve, and distinguish between sulfotyrosine and phosphotyrosine modifications using a set of model peptides. Multiple fragmentation techniques, namely HCD, CID, ETD, ETciD, and EThcD, have been used to compare the different fragmentation behaviors between peptides modified with these species. Sulfotyrosine undergoes neutral loss using HCD and CID, but the sulfuryl moiety is largely stable under ETD. In contrast, phosphotyrosine is stable during fragmentation using all these methods. This differential stability provides a mechanism to distinguish sulfopeptides from phosphopeptides. Based on the rigorous characterization presented herein, this work serves as a model for accurate identification of phosphotyrosine and, more challenging, sulfotyrosine, in complex proteomic samples. Graphical Abstract ᅟ.

Rapid Classification of Coffee Products by Data Mining Models from Direct Electrospray and Plasma-Based Mass Spectrometry Analyses

In coffee manufacture, analytical methods with high-throughput and cost efficacy are required for process development and quality control. Thus, we investigated the applicability of direct mass spectrometry methods to distinguish coffee products according to species, geographic origin and processing. We tested the performance of the established method direct-injection electrospray mass spectrometry (DIESI-MS) and the emerging method low-temperature plasma ionization mass spectrometry (LTP-MS). Both methods are capable of classifying coffee products, but DIESI-MS and LTP-MS yield complementary information about the chemical composition of the samples. DIESI-MS shows a broad molecular weight range of compounds. In contrast, LTP-MS detects mainly low molecular weight compounds, which correspond to quality-related ingredients, such as caffeine and purines. LTP-MS displays a high potential for rapid quality control measurements and online monitoring, because no sample processing is required. Data mining methods support the discovery of ‘important’ compounds, which are responsible for the discrimination between sample groups, and reveal associated chemical processes.

Comparison of direct mass spectrometry methods for the on‐line analysis of volatile compounds in foods

For the on-line monitoring of flavour compound release, atmospheric pressure chemical ionization (APCI) and proton transfer reaction (PTR) combined to mass spectrometry (MS) are the most often used ionization technologies. APCI-MS was questioned for the quantification of volatiles in complex mixtures, but direct comparisons of APCI and PTR techniques applied on the same samples remain scarce. The aim of this work was to compare the potentialities of both techniques for the study of in vitro and in vivo flavour release. Aroma release from flavoured aqueous solutions (in vitro measurements in Teflon bags and glass vials) or flavoured candies (in vivo measurements on six panellists) was studied using APCI- and PTR-MS. Very similar results were obtained with both techniques. Their sensitivities, expressed as limit of detection of 2,5-dimethylpyrazine, were found equivalent at 12 ng/l air. Analyses of Teflon bag headspace revealed a poor repeatability and important ionization competitions with both APCI- and PTR-MS, particularly between an ester and a secondary alcohol. These phenomena were attributed to dependency on moisture content, gas/liquid volume ratio, proton affinities and product ion distribution, together with inherent drawbacks of Teflon bags (adsorption, condensation of water and polar molecules). Concerning the analyses of vial headspace and in vivo analyses, similar results were obtained with both techniques, revealing no competition phenomena. This study highlighted the equivalent performances of APCI-MS and PTR-MS for in vitro and in vivo flavour release investigations and provided useful data on the problematic use of sample bags for headspace analyses.

Exhaled breath analysis for early cancer detection: principle and progress in direct mass spectrometry techniques

Volatile biomarker analysis in exhaled breath is becoming one of the desirable strategies for cancer detection because it may offer a relatively inexpensive, rapid, and non-invasive screening method for early diagnosis. Breath analysis has attracted a considerable amount of scientific and clinical interest over the past decade. However, breath is not yet used for routine medical diagnostic purposes. Challenges faced in the development of breath analysis for cancer diagnosis include developing techniques that can measure biomarkers in exhaled breath at ultratrace levels, providing definitive evidence for their presence and for the relationship between the proposed biomarker and the underlying condition. Various analytical methods are used for the detection of breath biomarkers. Gas chromatography-based methods which involve sample collection, analyte preconcentration, desorption, and separation steps are the most popular. However, direct-sampling mass spectrometry techniques have been proven more reliable for air analysis without prior sample pretreatment or chromatographic separation. This review focuses on the most commonly used direct mass spectrometry methods for the direct online analysis of endogenous cancer biomarkers in exhaled breath, with particular attention to principle of detection, method performance, advantages, shortcomings, recent advances, and applications within health-related studies for cancer biomarkers research. The principle behind the science of breath analysis for cancer diagnosis is also discussed.

Evaluating the physiological state of maize (Zea mays L.) plants by direct-injection electrospray mass spectrometry (DIESI-MS)

Climatic change is an increasing challenge for agriculture that is driving the development of suitable crops in order to ensure supply for both human nutrition and animal feed. In this context, it is increasingly important to understand the biochemical responses of cells to environmental cues at the whole system level, an aim that is being brought closer by advances in high throughput, cost-efficient plant metabolomics. To support molecular breeding activities, we have assessed the economic, technical and statistical feasibility of using direct mass spectrometry methods to evaluate the physiological state of maize (Zea mays L.) plants grown under different stress conditions.

Evaluation of three gas chromatography and two direct mass spectrometry techniques for aroma analysis of dried red bell peppers

Three gas chromatography methods and two direct mass spectrometry techniques were compared for the analysis of the aroma of rehydrated diced red bell peppers. Gas chromatography methods included systems with olfactometry detection (GC–O), flame ionisation detection (GC–FID) and mass spectrometry (GC–MS). The evaluated direct mass spectrometry techniques involved atmospheric pressure chemical ionisation–time-of-flight mass spectrometry (APCI–TOFMS) and proton transfer reaction–mass spectrometry (PTR–MS). The relevance of the aroma component of the flavour was shown by sensory analysis. High intensity scores were obtained for the aroma attributes ‘bell pepper,’ ‘cooked vegetables’ and ‘grassy.’ Sixty-three volatile compounds were identified in the headspace of the bell peppers by GC–MS. According to GC–O analysis, 11 compounds possessed odour activity. Consistently across all techniques, 3-methylbutanal was the most abundant odour active compound, followed by 2-methylbutanal. Compounds present at low concentrations were more affected by the methodology. Chromatography methods correlated strongly with each other (ρ=0.946), whereas the direct mass spectrometry methods showed less significant correlation (ρ=0.613). Examining differences across all methods, it appeared that the proportions of the odour active compounds were not significantly different for GC–MS, GC–FID and PTR–MS. Significant differences were observed for APCI–TOFMS and the other techniques (P<0.01).

Direct mass spectrometry of polymers. IX. Copoly(carbonate‐urethanes) prepared by reorganization of polycarbonates with piperazine

AbstractA detailed analysis of the reaction products generated by reorganization of polycarbonates with piperazine, performed by direct mass spectrometry methods, has shown that this reaction actually follows the pathway postulated and that, at 50% piperazine incorporation level, urethanediphenol compounds are almost exclusively produced. This allowed us to obtain, by repolymerization with phosgene, alternating copoly(carbonate‐urethanes) with thermal stabilities comparable to those of the parent polyurethanes. The primary fragmentation mechanisms in the thermal decomposition of these copolymers were studied by direct pyrolysis into the mass spectrometer. Ester exchange reactions predominate here, causing the formation of cyclic oligomers, which are subsequently cleaved to open‐chain oligomers containing hydroxyl end groups.