Development and validation of an ultrafast method of quantification of rivaroxaban in human serum using laser diode thermal desorption coupled to triple quadrupole mass spectrometry.

Rationale: Rivaroxaban is an anticoagulant prescribed to patients who are at risk of medical conditions such as deep-vein thrombosis, pulmonary embolisms, and strokes caused by blood clots. The administration of this drug is monitored to adjust the dosage and evaluate patients' blood concentration. Rapid quantification of this drug in plasma could make it possible to ensure that the dose present in the blood of patients does not represent a danger for the medical intervention to be carried out.

Automated High-Throughput Quantification of Phenyl-γ-valerolactones and Creatinine in Urine by Laser Diode Thermal Desorption.

Quantification of nutritional biomarkers is crucial to accurately assess the dietary intake of different classes of (poly)phenols in large epidemiological studies. High-throughput analysis is mandatory to apply this methodology in large cohorts. However, the current validated methods to quantify (poly)phenols metabolites in biological fluids use ultra performance liquid chromatography (UPLC), leading to analysis time of several minutes per sample.

A pandemic business interruption insurance.

We analyze how pandemic business interruption coverage can be put in place by building on capitalization mechanisms and a portfolio management strategy. As evidenced with COVID-19, pandemics affect economic sectors in differentiated ways: some are very severely affected because their activity is heavily impacted by travel bans and constraints on work organization, while others are more resistant. This opens the door to risk-coverage mechanisms based on a portfolio of financial securities, including long-short positions and options in stock markets.

COVID-19 crisis management in Luxembourg: Insights from an epidemionomic approach.

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg. The model has been used to produce nowcasts and forecasts at various stages of the crisis. We focus here on two key moments in time, namely the deconfinement period following the first lockdown, and the onset of the second wave.

Integration of Segmented Ion Fractionation and Differential Ion Mobility on a Q-Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer.

High-field asymmetric waveform ion mobility spectrometry (FAIMS) has gained popularity in the proteomics field for its capability to improve mass spectrometry sensitivity and to decrease peptide co-fragmentation. The recent implementation of FAIMS on Tribrid Orbitrap instruments enhanced proteome coverage and increased the precision of quantitative measurements. However, the FAIMS interface has not been available on older generation Orbitrap mass spectrometers such as the Q-Exactive.

Further studies on the signal enhancement effect in laser diode thermal desorption-triple quadrupole mass spectrometry using microwell surface coatings.

The laser diode thermal desorption (LDTD) ionization source allows ultrafast and sensitive analysis of small molecules by mass spectrometry. Signal enhancement in LDTD has been observed when coating the surface of sample microwells with a solution of ethylenediaminetetraacetic acid (EDTA) or nitrilotriacetic acid. Here we present a quantitative analysis of signal enhancement using solutions of diverse commercial proteins (lysozyme, immunoglobulin G, albumin, and fibrinogen) as coatings.

Signal enhancement in laser diode thermal desorption-triple quadrupole mass spectrometry analysis using microwell surface coatings.

Laser-diode thermal desorption (LDTD) is an ionization source usually coupled to triple quadrupole mass spectrometry (QqQMS) and specifically designed for laboratories requiring high-throughput analysis. It has been observed that surface coatings on LDTD microwell plates can improve the sensitivity of the analysis of small polar molecules. The objective of the present study is to understand and quantify the effect of microwell surface coatings on signal intensity of small organic molecules of clinical, environmental, and forensic interest.

Coupling Laser Diode Thermal Desorption with Acoustic Sample Deposition to Improve Throughput of Mass Spectrometry-Based Screening.

The move toward label-free screening in drug discovery has increased the demand for mass spectrometry (MS)-based analysis. Here we investigated the approach of coupling acoustic sample deposition (ASD) with laser diode thermal desorption (LDTD)-tandem mass spectrometry (MS/MS). We assessed its use in a cytochrome P450 (CYP) inhibition assay, where a decrease in metabolite formation signifies CYP inhibition.

Ultra-fast cyclosporin A quantitation in whole blood by Laser Diode Thermal Desorption-tandem mass spectrometry; comparison with High Performance Liquid Chromatography-tandem mass spectrometry.

In the last decade the quantitation of immunosuppressive drugs has seen vast improvements in analytical methods, optimizing time, accuracy of analysis and cost. Laser Diode Thermal Desorption (LDTD) coupled to Atmospheric Pressure Chemical ionization-tandem mass spectrometry (APCI-MS/MS) represents a technological breakthrough that removes the chromatographic separation step and thereby significantly increases the analytical throughput for the quantitation of cyclosporin A (CsA) in whole blood for therapeutic drug monitoring (TDM). A simple protein precipitation step was used prior to depositing 5 μL of the extract on a 96-well LazWell™ plate and CsA was quantified by LDTD-APCI-MS/MS.

Laser diode thermal desorption-positive mode atmospheric pressure chemical ionization tandem mass spectrometry for the ultra-fast quantification of a pharmaceutical compound in human plasma.

An ultra-fast, reliable and sensitive analytical method enabling high-throughput quantitative analysis of pharmaceutical compounds in human plasma is described. The quantitative work was performed on one of our compound currently under clinical trial by employing a deuterated internal standard (IS). Plasma samples were treated on solid phase micro-extraction (SPME) plates prior their analysis by laser diode thermal desorption and atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD/APCI-MS/MS) in positive mode.

High-throughput quantitation of seven sulfonamide residues in dairy milk using laser diode thermal desorption-negative mode atmospheric pressure chemical ionization tandem mass spectrometry.

Sulfonamides are antibiotic compounds widely used in the dairy industry. Their presence in diary milk poses a risk to public health and may also contribute to the spread of antibiotic resistance in bacteria. Sulfonamide residues in dairy milk were quantified by tandem mass spectrometry (MS/MS) using a novel ionization source based on laser diode thermal desorption-negative mode atmospheric pressure chemical ionization (LDTD-APCI(-)).

Direct atmospheric pressure chemical ionization-tandem mass spectrometry for the continuous real-time trace analysis of benzene, toluene, ethylbenzene, and xylenes in ambient air.

Real-time monitoring of benzene, toluene, ethylbenzene, and xylenes (BTEX) in ambient air is essential for the early warning detection associated with the release of these hazardous chemicals and in estimating the potential exposure risks to humans and the environment. We have developed a tandem mass spectrometry (MS/MS) method for continuous real-time determination of ambient trace levels of BTEX. The technique is based on the sampling of air via an atmospheric pressure inlet directly into the atmospheric pressure chemical ionization (APCI) source.

High-throughput cytochrome P450 inhibition assays using laser diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry.

This paper describes the development of a high-throughput method for the analysis of cytochrome P450 (CYP) inhibition assay incubation samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization mass spectrometry (LDTD-APCI-MS). Data for the CYP isoforms 3A4, 2D6, 2C9, and 1A2 from competitive inhibition assays are shown. The potential for inhibition of the CYP isoforms was measured by monitoring the level of the metabolites 6beta-hydroxytestosterone (3A4), dextrorphan (2D6), 4'-hydroxydiclofenac (2C9), and acetaminophen (1A2) formed in the presence of drug candidates using an eight-point titration.

Implications of proprotein Convertase 5 (PC5) in the arterial restenotic process in a porcine model.

Introduction: Convertases (PCs), especially PC5, have been detected in various layers of atherosclerotic and injured arteries. We postulate that PCs could be important enzymes in vascular disease thus studied PC5 expression in a porcine balloon and stent coronary arterial vascular injury model.

Methods: Immunohistochemistry and in situ hybridization of slides of porcine arteries from paraffin blocks were studied 1, 7, 14 and 28 days post injury.

Effects of VasoCare therapy on the initiation and progression of atherosclerosis.

VasoCare therapy, which involves the administration of autologous blood following the ex vivo exposure to physico-chemical stressors, has been shown to modulate immune responses. Since immune mechanisms have been recognized to be pivotal in the pathogenesis of atherosclerosis, we hypothesized that VasoCare treatment would inhibit atherosclerosis in LDL-R (-/-) mice. Three groups of LDL-R (-/-) mice were studied: a control group that was fed normal chow (Group I) and no other treatment; a control group that received a high cholesterol (HC) diet for 8 weeks (group II) with sham saline injections; and a third group (III) that received HC diet for 8 weeks and VasoCare treatment initiated after four weeks of HC feeding.