Fomepizole

News Summary: Waters combines the enhanced desorption electrospray ionization (DESI) source with the Xevo TQ Absolute tandem quadrupole mass spectrometer to enable faster and more sensitive targeted pre-clinical MS imaging experiments. 5X more sensitive and 5X faster than discovery-grade quadrupole time-of-flight MS imaging assays.i Enables pharmaceutical development scientists to decide which drug candidates to investigate further and develop into marketable drugs as quickly as possible. HOUSTON, June 5, 2023 /PRNewswire/ -- American Society for Mass Spectrometry (ASMS) -- Waters Corporation (NYSE:WAT) today launched the industry's first targeted imaging mass spectrometer based on its Xevo™ TQ Absolute tandem quadrupole mass spectrometer, the most sensitive and compact mass spectrometer in its class. The new instrument combines the Waters™ DESI XS source with the Xevo TQ Absolute system and is five times more sensitive and five times faster than discovery-based imaging systems at precisely determining whether a particular small molecule drug product – and how much of it - reaches its intended target, such as a brain, liver, or lung, in a test subject. Waters adds DESI XS source to its Xevo TQ Absolute mass spectrometer for fast and sensitive targeted MS imaging. "Customers have successfully applied the Xevo TQ Absolute system to solve a host of problems including PFAS testing at parts-per-quadrillion levels," said Jon Pratt, Senior Vice President, Waters Division. "Now, combining it with the DESI XS source gives drug development scientists a powerful new tool for efficiently evaluating the effects of drugs at the site of action with the statistical power of full studies." Dr. Jephte Akakpo, Post-Doctoral Research Fellow, University of Kansas Medical Center, is part of a team researching an antidote (fomepizole) to drug–induced acute liver and kidney damage caused by an acetaminophen overdose. "The DESI XS source features a high-performance sprayer and that makes the DESI source robust so we can work much more efficiently," said Dr. Akakpo. "Pairing it with the Xevo TQ Absolute system will greatly improve the signal-to-noise ratio and lets us test hypotheses in a way that we couldn't before. The system is taking quantitative MS imaging to the next level." Applications for direct-from-sample DESI/tandem quadrupole mass spectrometry include: Elucidating drug distribution in tissue sectionsii Monitoring relevant biochemical pathways in toxicological studies Classifying tissue and determining tumor margins At this year's ASMS conference, Waters is also showcasing its PFAS analytical workflow based on the ultra-sensitive Xevo TQ Absolute mass spectrometer, chemistries, and software. The end-to-end UPLC-MS workflow allows laboratories worldwide to upgrade their capability and keep current with the latest regulatory requirements for measuring parts-per-quadrillion levels of PFAS in air, water, soil, and food. Additional Resources Learn more about Targeted MS Imaging with the DESI XS and the Xevo TQ Absolute system. Download the DESI XS and Xevo TQ Absolute system brochure. Read the application note Improved Sensitivity for the Detection of PFAS in Environmental Water Samples Using a Direct Injection Approach on the Xevo TQ Absolute. Follow and connect with Waters via LinkedIn, Twitter, and Facebook About Waters Corporation ( ) Waters Corporation (NYSE:WAT), a global leader in analytical instruments and software, has pioneered chromatography, mass spectrometry, and thermal analysis innovations serving the life, materials, and food sciences for over 60 years. With more than 8,200 employees worldwide, Waters operates directly in 35 countries, including 14 manufacturing facilities, and with products available in more than 100 countries. Waters and Xevo are trademarks of Waters Corporation. Waters Contact: Brian J. Murphy PR Manager, Corporate Communications Waters Corporation brian_j_murphy@waters.com +1 508-482-2614 i Comparison to Waters high resolution MALDI or DESI-enabled discovery quadrupole time-of-flight MS imaging systems. ii Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies doi: 10.3390/metabo13030377 View original content to download multimedia: SOURCE Waters Corporation Company Codes: NYSE:WAT

Pneumococcal disease leads to over three million hospitalizations and hundreds of thousands of deaths annually. A new study suggests that the FDA-approved drug Fomepizole may reduce disease severity in the lungs of mice with some forms of bacterial pneumonia and enhance the efficacy of the antibiotic erythromycin as well. Pneumococcal disease leads to over three million hospitalizations and hundreds of thousands of deaths annually. A study publishing March 16 in the open access journal PLOS Biology by Carlos J. Orihuela at the University of Alabama at Birmingham, Alabama, United States, and colleagues suggests that the FDA-approved drug Fomepizole may reduce disease severity in the lungs of mice with some forms of bacterial pneumonia and enhance the efficacy of the antibiotic erythromycin as well. Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. While vaccines to protect against the bacteria are available, these vaccines are not effective against all strains, with some versions being especially problematic as they are multidrug-resistant. Currently, there are very limited treatment options for combating multidrug-resistant S. pneumoniae infections. In order to test the effects of novel treatments for antibiotic-resistant S. pneumoniae, the researchers conducted a series of experiments with mice. Fomepizole is an FDA-approved drug normally used as an antidote for the ingestion of toxic alcohols (such as methanol or ethylene glycol), and works by inhibiting the enzyme alcohol dehydrogenase. Researchers inoculated mice with a multidrug-resistant S. pneumoniae and tested the effect of fomepizole in a combinatorial treatment with antibiotics. They quantified the bacterial burden in the organs of infected mice, comparing the experimental group with the control group. The researchers found that using Fomepizole blocked normal energy production by S. pneumoniae and enhanced the bacteria's susceptibility to antibiotics and reduced bacterial burden in the lungs of mice with pneumonia. The combination treatment was effective in preventing the development of invasive disease. Future research is needed however, as this novel drug treatment has not been replicated in clinical studies on humans, who may present with complicating factors such as comorbidities, advanced age, or environmental variables that may play a role in disease outcomes. Orihuela adds, "Pharmacological targeting of fermentation pathways is a new way to enhance the susceptibility of some bacteriato antimicrobials. Combination treatment of erythromycin and fomepizole, an alcohol dehydrogenase inhibitor, prevented the in vivo dissemination of antibiotic-resistant Streptococcus pneumoniae."