Early detection of bacterial pneumonia by characteristic induced odor signatures.

Introduction: The ability to detect pathogenic bacteria before the onsets of severe respiratory symptoms and to differentiate bacterial infection allows to improve patient-tailored treatment leading to a significant reduction in illness severity, comorbidity as well as antibiotic resistance. As such, this study refines the application of the non-invasive Secondary Electrospray Ionization-High Resolution Mass Spectrometry (SESI-HRMS) methodology for real-time and early detection of human respiratory bacterial pathogens in the respiratory tract of a mouse infection model.

Methods: A real-time analysis of changes in volatile metabolites excreted by mice undergoing a lung infection by Staphylococcus aureus or Streptococcus pneumoniae were evaluated using a SESI-HRMS instrument.

Extracting Knowledge from MS Clinical Metabolomic Data: Processing and Analysis Strategies.

Assessing potential alterations of metabolic pathways using large-scale approaches plays today a central role in clinical research. Because several thousands of mass features can be measured for each sample with separation techniques hyphenated to mass spectrometry (MS) detection, adapted strategies have to be implemented to detect altered pathways and help to elucidate the mechanisms of pathologies. These procedures include peak detection, sample alignment, normalization, statistical analysis, and metabolite annotation.

A novel ultra-high-performance supercritical fluid chromatography hyphenated to tandem mass spectrometry method for the analysis of urinary endogenous steroids in the anti-doping context.

The first step in the detection of testosterone (T) doping is to measure the urinary steroid profile for the athlete biological passport (ABP). To harmonise the analysis between anti-doping laboratories, urinary steroid profiling is parametrised in deep detail and shall be performed by gas chromatography hyphenated to mass spectrometry (GC-MS). However, due to its requirement for extensive sample preparation, alternatives to GC-MS are being actively pursued.

Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids.

The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed.

Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials.

Hospital pharmacy compoundings are crucial for maintaining patient care. They are time- and cost-effective in hospital pharmacy settings because they prevent waste, preparation errors, dosage errors, microbial contamination and breakage due to handling. Unfortunately, the drawbacks of hospital pharmacy compounding include the selection of inappropriate medical devices (MDs) for long-term storage, which could directly impact patients.

Substantial benefits of an inert biphenyl column for the analysis of steroids and their phase II metabolites in biological samples.

Steroids can be used as biomarkers in clinical metabolomics and other fields related to human toxicology. This chemical group is known for its complexity, considering its number of isobaric compounds and the wide variety of phases I and II metabolic pathways that parent compounds can undergo. For a successful analysis of steroids in biological samples, liquid chromatography separation must be finely tuned.

Fast neonicotinoid quantification in honey using the one-point internal calibration approach.

Neonicotinoids, a highly effective class of insecticides used worldwide, have been identified as a major cause of concern for biodiversity. To assess the ecological and environmental consequences of neonicotinoids' use, reliable analytical methodologies, including calibration approaches, are needed. Here, we compared the performance of internal calibration (IC) using a single concentration of stable isotope-labeled standard (SIL) with classical multipoint external calibration (EC) for the quantification of six neonicotinoids in honey.

Hyphenation of microflow chromatography with electrospray ionization mass spectrometry for bioanalytical applications focusing on low molecular weight compounds: A tutorial review.

Benefits of miniaturized chromatography with various detection modes, such as increased sensitivity, chromatographic efficiency, and speed, were recognized nearly 50 years ago. Over the past two decades, this approach has experienced rapid growth, driven by the emergence of mass spectrometry applications serving -omics sciences and the need for analyzing minute volumes of precious samples with ever higher sensitivity. While nanoscale liquid chromatography (flow rates <1 μL/min) has gained widespread recognition in proteomics, the adoption of microscale setups (flow rates ranging from 1 to 100 μL/min) for low molecular weight compound applications, including metabolomics, has been surprisingly slow, despite the inherent advantages of the approach.

N-acetylglucosamine supplementation fails to bypass the critical acetylation of glucosamine-6-phosphate required for Toxoplasma gondii replication and invasion.

The cell surface of Toxoplasma gondii is rich in glycoconjugates which hold diverse and vital functions in the lytic cycle of this obligate intracellular parasite. Additionally, the cyst wall of bradyzoites, that shields the persistent form responsible for chronic infection from the immune system, is heavily glycosylated. Formation of glycoconjugates relies on activated sugar nucleotides, such as uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).

Assessment of the surface contamination of the primary packaging of oral antineoplastic drugs and secondary packaging of chemotherapy preparations at a Swiss hospital.

Introduction: Due to the high toxicity of antineoplastic drugs, handling their packaging could lead to the chemical contamination of hospital environments and exposure risks to healthcare professionals and patients. This study aimed to assess the contamination of two main surfaces: the outer primary packaging of oral antineoplastic drug formulations (  =  36) available on the Swiss market and the surface of secondary packaging of injectable antineoplastic drug preparations (  =  60) produced by the pharmacy of a Swiss hospital and carriers used for transport (  =  5).

Methods: Samples were collected using a validated wipe sampling method.

Development of a generic sample preparation method using dispersive liquid-liquid microextraction for the monitoring of leachable compounds in hospital pharmacy-prepared prefilled drug products.

Performant sample preparation is mandatory in any leachable study to clean and preconcentrate analytes within the sample to offer the best possible extraction recovery as well the best precision for any given substance. The aim consists in developing a sample preparation method for hospital pharmacy-prepared drug products such as long-term storage prefilled syringes, vials and IV bags for the screening of leachable compounds. The Quality Control Laboratory of the Pharmacy of the Lausanne University Hospital (Switzerland) has developed a time- and cost-effective, highly sensitive, robust, and fast method using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for the analysis of 205 plastic additives.

Comprehensive plasma steroidomics reveals subtle alterations of systemic steroid profile in patients at different stages of prostate cancer disease.

The steroid submetabolome, or steroidome, is of particular interest in prostate cancer (PCa) as the dependence of PCa growth on androgens is well known and has been routinely exploited in treatment for decades. Nevertheless, the community is still far from a comprehensive understanding of steroid involvement in PCa both at the tissue and at systemic level. In this study we used liquid chromatography/high resolution mass spectrometry (LC/HRMS) backed by a dynamic retention time database DynaSTI to obtain a readout on circulating steroids in a cohort reflecting a progression of the PCa.

Metabolites in the regulatory risk assessment of pesticides in the EU.

A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities.

Development of a generic approach for monitoring leachable compounds in hospital pharmacy-prepared prefilled plastic packaging by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry with postcolumn infusion.

Prefilled plastic packaging is time- and cost-effective in hospital pharmacy because it prevents waste, preparation errors, dosage errors, microbial contamination and accidents. This packaging mostly includes prefilled syringes (PFS), intravenous (IV) bags and vials intended for long-term storage that can be used for immediate treatment. There is a rising availability in the market for prefilled drug products due to their practical approach.

Multitargeted Internal Calibration for the Quantification of Chronic Kidney Disease-Related Endogenous Metabolites Using Liquid Chromatography-Mass Spectrometry.

Accurate quantitative analysis in liquid chromatography-mass spectrometry (LC-MS) benefits from calibration curves generated in the same matrix as the study sample. In the case of endogenous compound quantification, as no blank matrix exists, the multitargeted internal calibration (MTIC) is an attractive and straightforward approach to avoid the need for extensive matrix similarity evaluation. Its principle is to take advantage of stable isotope labeled (SIL) standards as internal calibrants to simultaneously quantify authentic analytes using a within sample calibration.

Targeted metabolomic profiling as a tool for diagnostics of patients with non-small-cell lung cancer.

Lung cancer is referred to as the second most common cancer worldwide and is mainly associated with complex diagnostics and the absence of personalized therapy. Metabolomics may provide significant insights into the improvement of lung cancer diagnostics through identification of the specific biomarkers or biomarker panels that characterize the pathological state of the patient. We performed targeted metabolomic profiling of plasma samples from individuals with non-small cell lung cancer (NSLC, n = 100) and individuals without any cancer or chronic pathologies (n = 100) to identify the relationship between plasma endogenous metabolites and NSLC by means of modern comprehensive bioinformatics tools, including univariate analysis, multivariate analysis, partial correlation network analysis and machine learning.

Straightforward quantification of endogenous steroids with liquid chromatography-tandem mass spectrometry: Comparing calibration approaches.

Different calibration strategies are used in liquid chromatography hyphenated to mass spectrometry (LC-MS) bioanalysis. Currently, the surrogate matrix and surrogate analyte represent the most widely used approaches to compensate for the lack of analyte-free matrices in endogenous compounds quantification. In this context, there is a growing interest in rationalizing and simplifying quantitative analysis using a one-point concentration level of stable isotope-labeled (SIL) standards as surrogate calibrants.

A new multimodal paradigm for biomarkers longitudinal monitoring: a clinical application to women steroid profiles in urine and blood.

Background: Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeling strategy to a multivariate score integrating several biomarkers (compound concentration and/or ratio).

A unified strategy to rebalance multifactorial designs with unequal group sizes: application to analysis of variance multiblock orthogonal partial least squares.

Background: Adequately handling unbalanced groups remains one of the major challenges for the analysis of multivariate data collected from multifactorial experimental designs. While partial least squares-based methods, such as analysis of variance multiblock orthogonal partial least squares (AMOPLS), can offer better discrimination between factor levels, they can be more heavily affected by this issue, and unbalanced designs of experiments may lead to a substantial confusion of the effects. Even state-of-the-art analysis of variance (ANOVA) decomposition methodologies using general linear models (GLM) lack the ability to efficiently disentangle these sources of variation when combined with AMOPLS.

Investigation of several chromatographic approaches for untargeted profiling of central carbon metabolism.

Monitoring the central carbon metabolism (CCM) network using liquid chromatography/mass spectrometry (LC-MS) analysis is hampered by the diverse chemical nature of its analytes, which are extremely difficult to analyze using single chromatographic conditions. Furthermore, CCM-related compounds present non-specific adsorption on metal surfaces, causing detrimental chromatographic effects and sensitivity loss. In this study, polar reversed-phase, mixed-mode (MMC), and zwitterionic hydrophilic interaction chromatography (HILIC) featuring low-adsorption hardware were investigated towards untargeted analysis of biological samples with a focus on energy metabolism-related analytes.

Gonadotropin axis and semen quality in young Swiss men after cannabis consumption: Effect of chronicity and modulation by cannabidiol.

Background: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus-pituitary-gonadotropic axis.

Objectives: To assess the impact of the consumption of Δ-9-tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men.

Extended steroid profiling in H295R cells provides deeper insight into chemical-induced disturbances of steroidogenesis: Exemplified by prochloraz and anabolic steroids.

Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times.

From fundamentals in calibration to modern methodologies: A tutorial for small molecules quantification in liquid chromatography-mass spectrometry bioanalysis.

Over the last two decades, liquid chromatography coupled to mass-spectrometry (LC‒MS) has become the gold standard to perform qualitative and quantitative analyses of small molecules. When quantitative analysis is developed, an analyst usually refers to international guidelines for analytical method validation. In this context, the design of calibration curves plays a key role in providing accurate results.