Special Issues-11-01-2008

Organic acids are present in many media and play various crucial roles. Low molecular mass organic acids (LMMOAs) have been researched extensively in many areas, such as food chemistry, as these acids affect taste, shelf-life, and food safety (1–3); agriculture, ecosystems, and environmental science, as these acids act as key components in mechanisms that some plants use to cope with environmental stress (4) and fertilizer release (5); biotechnology, to better understand and optimize fermentation processes (6,7); and biomedical research (8–11). Recently, LMMOAs were found to have inhibitory effects on the bioconversion efficiencies of lignocelluloses to ethanol (12).

At a symposium attended almost exclusively by practitioners of chromatography, the one thing they all wanted more of was mass spectrometry information.

Protein and peptide analysis via tandem mass spectrometry (MS-MS) has resulted in a wealth of information regarding protein identification, structure, and abundance levels over the past 10 years. Techniques such as neutral loss scanning and collision-induced dissociation (CID) have been especially helpful in facilitating the identification of a multitude of previously unknown sites of protein phosphorylation. However, many of the techniques used to obtain this information are labor intensive and work inconsistently. To address this problem, much effort has been put forth to find alternative methods of fragmenting peptides and proteins that are less difficult and applicable to a wide gamut of peptide classes. Examples of recently developed dissociation techniques include infrared multiphoton dissociation (IRMPD) and electron transfer dissociation (ETD). The implementation of these new techniques has widened the spectrum of peptides amenable to tandem mass spectral analysis.

The use of mass spectrometry (MS) in clinical diagnosis goes back to the early 1970s with the application of gas chromatography (GC)–MS to the determination of a variety of biologically significant molecules. Because GC requires a certain level of analyte volatility, and since most biologically active molecules are polar, thermolabile, and involatile, elaborate extraction and derivatization protocols needed to be devised to make GC–MS useful for the analysis of clinically relevant samples. To make sample analysis less difficult by MS there had been a significant amount of R&D invested over several decades aimed at coupling high performance liquid chromatography (HPLC) with MS since HPLC is a much better separation technology than GC for polar thermolabile biologically relevant molecules. This coupling was not without significant challenges; most of the LC–MS coupling techniques that evolved during the 1970s and 1980s were not very successful, and many of those that enjoyed some widespread..

Two decades ago, MS was the preserve of experts and skilled technicians as the instrumentation required constant attention and adjustment. At that time, liquid chromatography (LC)–MS was in its infancy and atmospheric pressure ionization (API) source interfacing was just beginning. Samples requiring analysis were passed from the requesting scientist to these "experts for analysis." The samples would be analyzed, processed, and interpreted, and the results returned via a written report. Two decades later, the users and capabilities of LC–MS have changed significantly. Now mass spectrometers and LC–MS systems are ubiquitous in the analytical laboratory, especially in the pharmaceutical industry. These instruments are used by a wide variety of scientists for a diverse range of tasks, from purity screening in medicinal chemistry, to the quantification of drugs in blood and the identification of proteins for biomarker discovery. The usability of the current MS platforms has improved..

With the globalization of trade, food production and distribution have become truly international businesses. When we dine out, the fish might come from Japan, the rice from Australia, the spices from China, and the strawberries from Mexico. We take it for granted that the food we eat is safe and free from contamination that could make us seriously ill.

For drug discovery workflows, the issue of metabolite detection and identification in in vivo systems is a critical challenge. The wide range of complex matrices (such as bile, plasma, urine, and fecal extracts), and the ion suppression effects of these biological fluids, can cause a severe decrease in the ability to detect metabolites. Greater instrument sensitivity is necessary to detect these compounds and, at the same time, helps to minimize sample preparation, simply diluting the negative effects of these complex matrices and avoiding the time- and labor-consuming sample cleanup or concentration steps that otherwise might be required.

For many years, and after several notable failures, many researchers were convinced that it was impossible to design a quadrupole time-of-flight (qTOF) mass spectrometer that was able to retain its ability to perform the high-resolution measurements necessary for definitive molecular formula determination of unknowns. Conventional wisdom indicated that there were many reasons (for example, temperature stability, ion diffusion, and ion loss on grids of reflectrons) that would make it impossible to improve resolution of these types of instruments. Figure 1 shows a schematic of an instrument designed for high-resolution measurements with fast chromatography (Maxis UHR-TOF mass spectrometer, Bruker Daltonics, Billerica, Massachusetts). The instrument includes an ion chiller, a series of ion refocusing operations, a single reflectron, and temperature control of the overall flight tube of the instrument.