Mass Spectrometry

In late-stage pharmaceutical development a new generation of high-resolution mass spectrometers and ion mobility mass spectrometers operate as orthogonal separation techniques and have greatly increased the ability to resolve impurities and increase the level of analytical information gained from a single analysis.

In the human food supply, public confidence is affected by contaminants and misreporting of nutritional information. This article highlights three events that required development of new mass spectrometry methods, including the detection of pesticides (such as fipronil and glyphosate), and the detection and quantification of fat-soluble vitamins.

HS-SPME-GC–MS is a valuable technique for identifying volatile organic compounds, additives, and degradation products in industrial rubber, car labeling reflection foil, and bone cement materials.

To address the challenges of analyzing new illicit drugs, emerging techniques such as UHPSFC with MS and UV detection, and GC with VUV detection, may be needed, particularly for distinguishing positional isomers and diastereomers.

LCGC, the leading resource for separation scientists, is proud to announce that Ronald E. Majors and Zachary S. Breitbach are the winners of the 11th annual LCGC Lifetime Achievement and Emerging Leader in Chromatography Awards, respectively. Majors and Breitbach will be honored in a symposium as part of the technical program at the Pittcon 2018 conference in Orlando, Florida, on February 26, 2018.

Tips for effective use of chromatography and mass spectrometry for the analysis of antibody–drug conjugates, glycoengineered proteins, and biosimilars.

Under a suitable thermal oxidation regime, vegetable oils yield a mixture of volatile and semivolatile organics that exhibit very high antimicrobial activities against a variety of microbial species. Volatile and semivolatile products were characterized with GC–MS using electron ionization and chemical ionization. The thermal oxidation of vegetable oils resulted in the formation of an array of short and medium-chain acids, aldehydes, and ketones that act synergistically to yield a potent antimicrobial disinfectant.

Since glycans are responsible for bioactivity, solubility, immunogenicity, and clearance rate from circulation, it is vital to have a detailed map of glycans in therapeutic glycoproteins. Detailed glycoprotein structural analysis must be able to identify the peptide sequence where the glycans are attached as well as the structure of the glycan portion, including oligosaccharide sequence and glycosyl linkages. This article details methods for mass spectrometry experiments on both released glycans (“glycomics”), as well as on intact glycopeptides (“glycoproteomics”) using electron transfer dissociation, high-energy collision dissociation, and collision-induced dissociation fragmentation pathways, which are needed to fully elucidate the structure of glycoproteins.

Wastewater analysis has become an established approach for retrieving additional epidemiological information about the use of illicit drugs, alcohol, and tobacco at the population level. Here, we present an overview of the recent analytical frameworks and workflows for target and suspect analyses using low- and high-resolution mass spectrometry and discuss the latest advances in wastewater-based epidemiology (WBE).

The disinfectants commonly used to treat public drinking water can react with naturally occurring organic and inorganic matter in the source water to form disinfection byproducts such as haloacetic acids. Here, we describe the use of two-dimensional matrix-elimination ion chromatography (MEIC) for haloacetic acid analysis. This method minimizes the impact of matrix ions.

Leading separation scientists share their perspectives on current challenges in separation science and where the field is heading.

In this study, general extract screening of food storage materials was done with nontargeted analytical methods to understand what analytes could potentially leach into food or beverages. GC and mass spectral deconvolution effectively separated analytes within the complex mixture and TOF-MS provided full mass range spectral data for identification. This workflow can be used for confident characterization of components present as extractables from food packaging materials.

There is growing interest in the determination of endogenous proteins in biological samples for diagnostic purposes, because a concentration increase or decrease of such proteins can allows us to monitor the state of a pathological condition such as cancer. Immunocapture LC–MS/MS analysis combines the workflow of conventional immunological assays with LC–MS analysis. This article describes typical challenges, such as cross reactivity and the mass spectrometer’s dynamic range, as well as the advantages of isoform differentiation and multiplexing.

Interest in connecting ion mobility spectrometry (IMS) to GC and especially to LC is now growing. One favorable property of IMS is that it can work with ambient pressure and can be easily connected to a gas or liquid chromatograph. Analytical applications of GC–MS and LC–MS are very different and encompass investigations into food, medical science, environment, drugs of abuse, chemical warfare agents, and explosives.

In drug development, quantitative determination of a candidate drug and its metabolites in biofluids is an important step. The standard technique for quantitative metabolite profiling is radiolabeling followed by HPLC with radiodetection, but there are disadvantages to this approach, including cost and time, as well as safety and ethical concerns related to administering radiolabeled compounds to humans. Frank Vanhaecke and his research group at Ghent University have been developing an alternative technique, and he recently spoke to us about this work.

We present a brief review of this year’s ASMS conference, which took place June 4–8 in Indianapolis, Indiana.

A model set of analytes and selected applications are used to demonstrate the effects that buffers can have on the selectivity of a separation and the sensitivity of a reversed-phase analysis when using MS detection.

Buffers are commonly used in reversed-phase liquid chromatography (LC) to control the ionization state of analytes. However, the addition of buffers is much more complex than simple pH control. Complex equilibria exist between these mobile-phase additives, the analytes, the silica surface, and even the stationary phase in certain circumstances. The addition of mass spectrometry (MS) as a primary detection technique makes decisions about mobile-phase additives even more crucial. In this column instalment, we use a model set of analytes and selected applications to demonstrate the effects that buffers can have not only on the selectivity of a separation, but also on the sensitivity of a reversed-phase analysis when using MS detection.

With computational chemistry, chemists can now study chemical phenomena by performing computationally intense calculations on computers rather than examining reactions and compounds experimentally. This is especially attractive when the laboratory experiments are time consuming, costly, dangerous, or difficult. Modern computational chemistry tools are capable of determining molecular structures, molecular spectra, and energetics, and of elucidating reaction pathways and chemical reaction products.

The analysis of oil samples containing many thousands of constituents best illustrates the benefits of ion mobility MS for complex samples. Here, we test the limits of ion mobility MS to discern differences between batches of Copaxone, a highly complex drug containing billions of peptides, and various purported generic versions of the drug.

Simultaneous, enantiomer-specific identification of chiral molecules in multicomponent mixtures is extremely challenging. With mass-selected photoelectron circular dichroism (MS-PECD) using an electron–ion coincidence imaging spectrometer, a compound can be identified as chiral without the need for any prior enantiomeric separation or enantiomer-selective complexation.

In this study, a simple method was used for extraction and concentration of trace organic compounds in water, followed by injection using a coiled wire filament and GC–MS analysis. Common semivolatile organic compound contaminants at low parts-per-billion levels were detected in less than 10 min.

A new peptide mapping method was developed specifically for mAb characterization that employs optimal enzyme pH for robustness, but with short digestion times and time-course elements to minimize and monitor deamidation–isomerization, respectively, enabling a more accurate assessment of potential CDR sequence liabilities.

When adhering to sound analytical principles, the inclusion of mass spectrometry in the clinical laboratory can lead to accurate, selective, and precise quantitative methods by detecting new classes of compounds with greater efficiency and sensitivity than is possible with older, established technologies.

With this method, a single injection was sufficient to characterize the amino acid sequence with complete sequence coverage. In addition, glycosylation and drug-loaded peptides could be identified from MS/MS spectra. A drug-loaded peptide fragmentation mass spectra study yielded drug-specific fragments, which reinforced the confidence about the identifications. The results reveal the ability of the sheathless CZE–MS/MS method to characterize an ADC’s primary structure in a single experiment.