Columns | Column: MS - The Practical Art

While immunoassay (EIA) is a prevalent screening technique it is also prone to issues such as high false positive rates because of lack of analyte specificity. Mass spectrometry was therefore investigated as an alternative screening technique for the ability to improve analyte specificity on a comparable time scale. In this study, a rapid online sample preparation and injection method was developed using a commercially available guard cartridge on a conventional LC–MS-MS system. Using a two-point calibration curve to provide semi-quantitation, a robust method was developed and validated that improved upon the high false positive rate observed in immunoassay screening.

The past decade has brought exponential growth in the number of mass spectrometry (MS) ionization techniques based on desorption and ionization (DI) processes. Here, the three key applications for DI are discussed: rapid, in situ screening; direct analysis of extracted samples or of planar chromatography spots; and scanning samples along x and y axes.

Non-targeted metabolite profiling by ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC–MS) is a powerful technique to investigate the influence of genetic and environmental influence on metabolic phenotype in plants. The approach offers an unbiased and in-depth analysis that can reveal molecular markers of desirable phenotypic traits which can be complementary to genetic markers in plant breeding efforts. Here, the power of non-targeted metabolite profiling is illustrated in a study focused on the determination of molecular markers in malting barley that are predictive of desirable malting quality for brewing applications.

Ion-mobility spectrometry (IMS) is an anlytical technique that provides for the separation of ions in the gas phase. The separation, occuring on a timescale of milliseconds, is based on the differing mobility of ions according to their charge, shape, and size. These characteristics make IMS suitable for coupling with mass spectrometry (MS), to serve in current MS-based workflows for metabolomics and lipidomics. IM-MS improves peak capacity and signal-to-noise ratios, and it provides more confidence during compound identification or confirmation than conventional analyses. Combining collision-induced dissociation with ion-mobility separation improves the specificity of MS/MS-based approaches. Significantly, ion-mobility-derived information provides an orthogonal, physicochemical parameter-the collision cross section (CCS)-which relates to a metabolite's shape. Novel hardware and software solutions enable analysts to process and exploit IMS-MS data for qualitative and quantitative metabolomics and lipidomics applications.

We have developed a miniaturized, multifunctional device, called the "Single-Probe," that is capable of probing small targets and of sampling and ionizing molecular species.

The use of a mass spectrometer in quantitative analysis exploits its exquisite selectivity and sensitivity as a detector, allowing a signal to be ascribed to a particular chemical entity with high certainty, even when present in a sample at a low concentration.

A review of the essential elements of MS approaches to protein quantification and a critical comparison of the available options

The chemistry of radicals - which is quite different from that of even-electron species - opens up new analytical capabilities.

A look at the various strategies and tools related to metabolomics applied to food and nutrition

A discussion of the future role of miniature MS systems, the need for simplification in operation, the role of ambient ionization, and challenges in development and commercialization.

Correlating biological activity with chemical composition is the Holy Grail of natural product chemists. Is mass spectrometry the right tool for this challenge?

A method using HR-MS systems to characterize the structures of metabolites is presented. The result is a general workflow for metabolism studies in drug discovery and development.

HDX-MS as a means for performing routine biophysical analysis

This analytical approach can be applied in many fields; the example illustrates its use in a food chemistry application.

A systematic approach for the identification of nontargeted species, searching both mass spectral and "spectra-less" databases

An interview with Fred McLafferty, professor emeritus at Cornell University, about his pioneering career in mass spectrometry

Multidimensional LC can automate sample preparation and provide a convenient way to analyze a sample with complementary columns.

This instalment provides a brief overview of some multidimensional approaches targeted at intact protein analysis for life science applications, particularly for biopharmaceutical analysis.

An overview of applications of various types of MS systems in drug discovery efforts, including in vitro and in vivo screening assays.

Mass spectrometry analysis of lipids in complex matrices is revolutionizing the way lipid research is conducted.

Part I of this series explains how lipids analysis has evolved.

How does one decipher and tabulate thousands of chemical formulas and relative abundances without losing the important details?

Coping with extractables and leachables testing is easier when you have a good understanding of the issues involved. Information from public databases and industry consortia also is invaluable.

Identifying unknown compounds continues to challenge analysts.

On the 50th anniversary of the invention of the laser, Michael Balogh examines its importance in MS practice.

In mass spectrometry, the electrospray ionization technique quickly earned its place among the primary analytical tools. Yet it is not always the best tool for the job.

With the advances in LC-MS in recent years, is there another practical option on the horizon for those who need the specificity of MS and can justify the narrow definition of a purpose-built system?

This month's installment addresses some elementary aspects of the mass spectrum, the tools employed by the experienced practitioner, and advances being made into identifying unknowns.

Michael Balogh uses examples such as the recent acetonitrile shortage to examine the topic of "the unknowable" as it pertains to separation science.

In this installment of "MS-The Practical Art," guest columnist Jack Henion presents an historical and practical overview of lab-on-a-chip (LOC) research and the commercial achievement associated with it so far.

Columnist Michael Balogh looks back on a 1997 LCGC article he wrote, and examines how many technological advances the field of MS has witnessed in the decade since.

Columnist Michael Balogh looks at the questions: Where are we now? What do the early MS innovators see as their legacy? And what can we expect in the future?

The use of mass spectrometry to study biofuels is examined and the advantages and disadvantages are explored.

This column completes the multipart MS primer with a list of terms derived from common usage throughout various industries.

Part III concludes the print version of our three-part series, "A Mass Spectrometry Primer," with the glossary to follow in a fourth and final installment.

Part II of this three-part series focuses on comparing operation and performance of the most well known mass spectrometers.

Michael Balogh begins a three-part overview series, answering questions about mass spectrometers, their use and capabilities, and including links to more detailed further reading in readily available articles written for the nonspecialist.

The matter of perfluorinated compounds (PFCs) came to focus at the United States Environmental Protection Agency (EPA) some eight years ago.

Recent work suggests that the practical value of hyphenated techniques is limited by difficulties inherent in achieving definitive compositional answers in general MS. This article argues that it is not impossible in certain cases.

This month's column discusses the practicalities of detecting substitutions in counterfeit pharmaceuticals. The approaches used are practical "take home" lessons readers can apply to analyse unknowns in any mixture.

This month, guest columnists Kind and Fiehn discuss small-molecule structure elucidation (excluding peptides) using hyphenated chromatographic techniques, mass spectrometers, and other spectroscopic detectors.

Nearly a dozen incipient technologies have appeared in recent years. Which will survive? Which will find extensive, robust usage as did electrospray ionization? Which are fated to become footnotes in mass spectrometry practice?

This month's instalment of "MS in Practice" provides a slightly different view of how practitioners employ the skills of interpretation that have been the focus in recent columns.

"As research advances, about half of what we will teach you . . . will turn out to be wrong. The problem is, we presently don't know which half." Powerful Medicines, Jerry Avorn, 2004

This month's installment of "MS - The Practical Art" provides a slightly different view of how practitioners employ the skills of interpretation that have been the focus in recent columns.

This month's column brings much of the previous discussion on how to interpret mass spectra to a practical examination of detecting substitutions in counterfeit pharmaceuticals.

Electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) are now among the most commonly used techniques for creating ions, especially from small-molecule compounds in solution. They have become so familiar that now many articles only refer to them briefly. Yet each technique has dramatic predictive strength on the outcome and limits of an analysis.

In this month's "MS-The Practical Art," Michael Balogh takes a closer look at insight provided by Chuck McEwen regarding obstacles while using solvents.

This month's installment of "MS - The Practical Art" reprises a talk from Chris Lipinski that examines the analytical road ahead in drug discovery and the quest to expand the chemistry landscape and its inherent analytical demands.

Although interpreting MS spectra can be a thorny problem at least some of the time, in the words of Fred McLafferty, "All you are dealing with is the mass of the molecule and the masses of the pieces."

October 2006. This month's "MS - The Practical Art" will interest those starting a new good laboratory practices (GLP) bioanalytical laboratory, reassessing an existing lab, or revamping a "spirit-of-GLP" laboratory to full GLP status.

Producers of mass spectrometers design their instruments to work well within specific parameters.

In Part I of this two-part look at spectral interpretation, Michael Balogh examined the ability to see and appreciate the product of our analytical devices. In Part II, he takes a closer look at the tools of the trade.

In this column, Michael Balogh proposes some practices that you can adopt to enhance your prospects of being right when converting data to knowable information and applying it to solving problems.

An increasingly available and attractive clinical analysis method, LC?MS nevertheless fails to directly benefit from the knowledge and experience of clinicians steeped in the immunoassay tradition.

This month's column explores the idea that despite the well-considered physics and engineering involved in mass spectrometer technology, it nonetheless seems that the uality of one's results are as much the product of art as they are of science.

The Centers for Disease Control and Prevention (CDC) estimates that each year in the United States, 76 million people get sick, 325000 are hospitalized and 5000 die from food-related illnesses. Food-borne illness is a serious public health problem. -National Library for the Environment, Food Safety Issues in the 107th Congress, 2001, Donna U. Vogt.

Few areas of LC-MS practice have been so affected by geopolitics as that of food safety analysis, a topic as important as it is complex. here, Michael Balogh examines this topic.

Where the wizard stands behind the curtain working levers.

In this initial instalment, several MS technologies and strategies currently being applied to characterize drug candidates in early stage development are presented.

Columnist Michael Balogh explores the topics of informatics and data management with this month's featured scientists.

process is interesting and involved, and in this month's installment of "MS - The Practical Art," Michael Balogh continues the Profiles in Practice series by exploring this topic with featured scientists Michele Kelly and Mark Kershaw.

This month’s column provides an overview of several recently developed technologies that aim to improve the utility and performance of mass spectrometers in a number of applications.

In this initial installment of "MS - The Practical Art," a new series of columns is introduced that investigates various aspects of mass spectrometry (MS) from the perspective of some leading practitioners. Here, featured scientists Kathleen Cox and Timothy Baker discuss several MS technologies and strategies currently being applied to characterize drug candidates in early stage development.

The authors discuss the issue of meeting the demands of regulatory compliance whilst ensuring good scientific practice. A number of requirements from 21 CFR Part 11 are cited to demonstrate the importance of applying the principles of risk analysis.

The authors look at how achieving both greater throughput and increasing informational content is a driving force in small-molecule analysis. They describe how analysts should address mechanical increases in productivity, software implementation flow and data management, and effective sample preparation to improve efficiency and reduce frustration.

Increase efficiency, not frustration, in small-molecule practices.

In the second instalment of this newly introduced column, Michael Balogh looks at resolution and mass accuracy as important considerations for determining the suitability of a mass spectrometer for an intended purpose.

"A well-prepared sample, a well-defined analytical goal, the appropriate use of accurate mass, reproducible retention times, and good instrument control generate unassailable data..."

In the first of this new column, Michael Balogh takes a look at source design and the strengths of multimode ionization, such as its ability to switch at high speeds between electrospray and atmospheric-pressure chemical ionization.