Mass Spectrometry

An overview of modern approaches to small-molecule drug discovery.

Better sample preparation and miniaturized separations are enhancing these analyses.

Sample preparation and analysis of pharmaceuticals in wastewater present unique challenges. Here, we describe those challenges.

The recruitment of young, talented entrepreneurs within academia and industry is needed to tackle many of the challenges that exist today and that will emerge tomorrow.

Further miniaturization of separations will greatly extend the reach of single-cell proteomics, metabolomics, and lipidomics, but key challenges in instrumentation, column technology, and ionization sources must be addressed.

Top-down mass spectrometry (TD-MS) of peptides and proteins results in product ions that can be correlated to the polypeptide sequence. Joseph Loo and colleagues at the University of California-Los Angeles (UCLA) have developed ClipMS, an algorithm assigning both terminal and internal fragments generated by TD-MS fragmentation, which can be used to locate various modifications on the protein sequence.

Ion mobility–mass spectrometry (IM–MS) has become a cornerstone of bioanalytical laboratories. New developments could lead to its widespread adoption for regulated bioanalysis methods such as anti-doping testing for anabolic steroids in athletes.

With the advent of ambient ionization and portable mass spectrometers, the ability to perform rapid, on-site analysis is fast becoming a reality. We review the critical recent developments enabling this capability as well as remaining challenges that must be tackled to enable widespread adoption.

Acoustic ejection mass spectrometry (AEMS) has recently emerged as the premier ultrahigh-throughput mass spectrometric methodology for drug discovery and related fields.

Using a mass spectrometer as a gas chromatography (GC) detector has many advantages for compound identification and quantification, but there is another less-known benefit: speeding up analyses by using the mass spectrometry (MS) vacuum to lower pressure within the column. This technique, also known as “vacuum‑outlet GC” or “low-pressure GC–MS” (LPGC–MS), can provide significant gains for fast GC–MS.

Separations science within microfluidics has already begun to make significant impact across any number of fields. But many times they are embedded within a larger system—their importance hidden or minimized.

In this next installment of our “Critical Evaluation” series, we will examine gas chromatography methods which use mass spectrometric detection (GC–MS).

By using MS-based techniques, thousands of metabolites can be measured.

Employing ion mobility at atmospheric pressure without vacuum enables coupling to high-resolution mass analyzers. High performance ion mobility–orbital trap mass spectrometry (HPIM-OT-MS) is a useful alternative for separating isomers, such as isomeric metabolites seen in drug discovery.

Multidimensional liquid chromatography (MDLC) methods have revolutionized the characterization of complex drug modalities like antibodies–drug conjugates, antisense oligonucleotides, and small interfering RNA therapeutics.

The study of the thermal behavior and pyrolysis products of these terpenoids could possibly suggest flavor precursors that could be used to provide specific flavors.

Measuring volatile phenols in wine is essential in ensuring superior wine quality. A new analytical technique, called solid-phase mesh-enhanced sorption from headspace (SPMESH), was modified with direct immersion (DI) conditions and coupled to direct analysis in real time–mass spectrometry (DART–MS) to be used to detect smoke taint in winemaking.

High resolution time-of-flight mass spectrometry (HR-TOF-MS) with a novel multimode ionization source together with enhanced chromatographic resolution can successfully detect and identify pollutants in household dust samples. Here’s how.

Our annual review of new high performance liquid chromatography instruments, mass spectrometry systems, and data processing software.

Newer direct-injection mass spectrometry techniques can improve real-time monitoring of volatile organic compounds.

High-resolution mass spectrometry (HRMS) is an increasingly critical tool for identifying, characterizing, and monitoring attributes of protein-based therapeutics.

Glen Jackson, Professor of Forensic and Investigative Science at West Virginia University, presented an "Expert Algorithm for Substance Identification (EASI): A New Paradigm for Mass Spectral Identifications" at SciX 2021, where it earned the FACSS Innovations Award. These awards are given for the most innovative and outstanding new research advancements debuted orally at the SciX Conference. Jackson spoke to Current Trends in Mass Spectrometry about his presentation.

Charge detection mass spectrometry (CDMS) is a useful tool to characterize larger, more complex biopharmaceuticals like bispecific antibodies and ADCs.

Understanding the design and operation of a quadrupole mass analyzer can help you plan, optimize, and troubleshoot analytical methods.

The presence of per- and polyfluoroalkyl substances (PFAS) in products used every day by millions of people is a cause of concern among both consumers and scientists. PFAS found in drinking water and the environment can cause serious health issues in animals and humans. Amanda Belunis, who is a PhD candidate at the University of Maryland in Baltimore County, has been investigating the use of liquid chromatography­­–tandem mass spectrometry (LC–MS/MS) to detect PFAS from a variety of environmental sources. She spoke with us about methods used to detect PFAS and described a new method that she and her team have developed to enhance PFAS detection.

QuEChERS has been updated to suit modern instrumentation. Now also “efficient and robust,” QuEChERSER is a “mega-method” that covers a wider polarity range.

Intact mass analysis is becoming increasingly useful for characterizing biologics. We describe the current application of intact mass analysis, including quantitation, sequencing, and structural characterization.

Stefan A. Pieconzonka and Philippe Schmitt-Kopplin have profiled diverse beer samples by rapid flow-injection analysis (FIA) Fourier transform ion cyclotron mass spectrometry (FTICR–MS). Here, they discuss their approach to this analysis, along with the significance of the Maillard Reaction (MR) in beer quality and analysis.

Interest in three-dimensional (3D) printing technology is expanding rapidly. What impact can it have in mass spectrometry? Robert Winkler, of the Center for Research and Advanced Studies Irapuato, in Guanajuato, Mexico, is exploring this question. We recently spoke with Prof. Winkler about this work.

The UHPLC–MS/MS method can accurately determine the presence of these illegal feed additives in swine tissues.