Mass Spectrometry

A number of clinical situations now call for high-sensitivity measurement of estrogens, including monitoring during female hormone replacement therapy, antiestrogen treatment, and estrogen deficiency in men. Traditional immunoassay methods and liquid chromatography–tandem mass spectrometry (LC–MS-MS) do not provide the sensitivity and selectivity required for these applications. In contrast, a gas chromatography–negative chemical ionization–tandem mass spectrometry (GC–NCI-MS-MS) platform can provide detection limits below 1 pg/mL when used in conjunction with the appropriate derivatization protocol, with very short cycle times.

Crude oil is a generic term for the unrefined flammable liquid that is mined from the ground. It is an extremely varied and very complex medium that can contain many thousands of organic compounds, whose contents and concentrations vary enormously from one sample to another. This article discusses how recent advances in time-of-flight-mass spectrometry coupled with comprehensive two-dimensional gas chromatography is helping the petrochemical industry to characterize crude oils more fully and so provide solutions to common problems experienced during drilling, extraction, and refining.

The misuse of androgenic anabolic steroids in sports was banned in 1976 by the International Olympic Committee and global sports community. The illegal use of anabolic steroids has reached disturbing levels worldwide. This worldwide problem is fueled partially by an ever-increasing demand for better athletic performance. The World Anti-Doping Agency has formulated strict guidelines for minimum allowable concentrations of exogenous anabolic steroids and their metabolites. The standard test methods for doping control are analyzed in urine samples with trimethyl-silyl derivatization. Urine is a complex and difficult biological matrix. This research shows the advantages of using comprehensive two-dimensional gas chromatography–time-of-flight-mass spectrometry (GCÃ-GC–TOF-MS) and illustrates the capability of GCÃ-GC-TOF-MS to be an effective instrumental option for antidoping control screening.

Adapting the use of "ultrahigh" performance chromatography for liquid chromatography–mass spectrometry (LC–MS) applications requires specific considerations in integrating the instrument platforms. Mobile phase options are limited to volatile buffers, and slow MS sampling rates can limit throughput advantages that such next-generation media offer. High-throughput LC–MS methods of different relevant pharmaceutical and environmental mixtures were developed using ultrahigh performance core-shell media. Such methods were developed using standard HPLC systems and back pressures, showing the ease and utility of using core-shell media for increasing throughput of LC–MS methods.

Those fond of puns point out that mass spectrometry (MS) has become ever more focused in the last two decades, while at the same time offering ever more information. The dynamic market for biotherapeutics has driven a number of developments, particularly following the paradigm of well-characterized biopharmaceutical products (WCBP) (1,2). Partly as a result of automation and interfacing, those trained in biological or biochemical disciplines now use mass spectrometers routinely. This also means that the sorts of questions asked of MS have changed. Coping with biomolecule heterogeneity is a key challenge, not generally an issue for small molecule drugs. The data complexity means that mass information alone is insufficient. And at the submission stage, regulators are increasingly concerned about tertiary structure and conformation, something that was not previously an analytical requirement (2). Adding polyethylene glycol (PEG) to already heterogeneous molecules to prolong their half-lives in the body raises..

A person-portable gas chromatography–mass spectrometry (GC–MS) system employing a toroidal ion trap mass spectrometry (TMS) detector was used to analyze chemical threat related compounds. Introduction of analytes into the heated injector of the instrument was by solid-phase microextraction (SPME), and fast resistive heating of a low thermal mass (LTM) gas chromatography column assembly provided rapid analysis times. Methodology for positive identification of chemical threats can combine chromatographic retention time, comparison to traditional electron ionization mass spectral libraries, and observation of expected pseudomolecular ions produced through self-chemical ionization. Methods are discussed for sampling by SPME with GC–MS analysis in the field to measure airborne analyte concentrations.

In preclinical development, the absolute quantification of peptides in biological matrices becomes a challenge due to the limited availability of stable label internal standards and affinity-based cleanup. This puts a renewed emphasis on matrix effects, especially for the bioanalysis of hydrophobic peptides. While the impact of matrix effects has been studied for extensively singly charged small molecules, their effect on multiply charged compounds has yet to be characterized fully. This article discusses initial results from matrix effect experiments in relation to the bioanalysis of hydrophobic peptides and techniques used to minimize matrix effects.

Mass spectrometry plays an increasingly significant role in the analysis of residues and contaminants in food. Here we will illustrate how the combination of ultrahigh-pressure liquid chromatography (UHPLC) and high-resolution time-of-flight-mass spectrometry (TOF-MS) is used to generate a screen of veterinary drug residues in products of animal origin. The use of UHPLC–TOF-MS and dedicated, workflow directed software allows rapid screening for large numbers of residues and automated quantification of positive samples. In addition, we illustrate how the data generated using MSE acquisition mode enable critical structural information to be collected, which offers additional selectivity and confirmatory data for compound identification and facilitates elucidation of the structure of newly discovered compounds.

The analysis of amines by gas chromatograph ;mass spectrometry (GC–MS) using electron ionization (EI) has always been a challenge

Liquid chromatography coupled to mass spectrometry (LC–MS) using electrospray ionization (ESI) is a powerful analytical tool for the analysis of a wide molecular weight range of polar, semivolatile, and thermally labile compounds.

Accurate, sensitive, and comprehensive characterization of monoclonal antibodies is an absolute necessity to the pharmaceutical and diagnostic industries to meet regulatory requirements and ensure the efficacy and safety of the final product. Microfluidic chip-based high performance liquid chromatography technology interfaced with the mass accuracy of quadrupole time-of-flight mass spectrometry provides the ability to rapidly and efficiently assess the quality of intact monoclonal antibodies, confirm their amino acid sequence, and determine their glycosylation state, while consuming very small amounts of these precious products.

Two-dimensional gas chromatography–time-of-flight mass spectrometry (GCÃ-GC–TOF-MS) analysis has emerged as one of the technologies of choice for the analysis of small metabolite profiles. The results of these analyses produce substantial quantities of data that can be extremely time-consuming and labor-intensive for the analyst to interpret. New software provides a tool for the scientist to use as a data-mining strategy to find significant results from large, complex data sets. This proof of concept research was conducted using comprehensive GCÃ-GC–TOF-MS to elucidate the small-molecule metabolite profiles of diabetic and nondiabetic urine in search of key differences between disease-state and nondisease-state individuals.

According to the Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG), techniques with the highest discriminating power should preferentially be used for forensic identification of seized drugs.

A prerequisite for a successful biotherapeutic formulation is one where the protein is stable and correctly folded.

Columnist Kenneth L. Busch discusses some of the basic considerations for valid sampling, with some examples pertinent to mass spectrometry.

NASA scientists have detected the amino acid glycine in samples of the comet Wild 2 gathered by the spacecraft Stardust.

The development of a method for the simultaneous determination of glycine, triglycine and fructose using UV–vis and evaporative light-scattering detection (ELSD) is described. This was necessary as part of a research project dealing with the recovery of functional peptides from aqueous streams on an industrial scale using adsorption or related technologies. Fructose is barely detectable by UV–vis as it lacks detectable functionalities, while glycine and triglycine are both UV–vis sensitive. An NH2 phase was chosen as a column and separation was obtained within seven minutes on a 250 X 4.6 mm column. Limits of detection are approximately 40 mg fructose/L, 4 mg glycine/L and 0.05 mg triglycine/L. Calibration functions are linear in a range of 40–1400 mg/L for fructose, 5–200 mg/L for glycine and 0.5–70 mg/L for triglycine.

The authors discuss improvements in sample preparation for ADME/pharmacokinetic studies of therapeutic oligonucleotides.

In this article, the authors review the capabilities and challenges of deploying mass spectrometry (MS) to homeland security screening requirements.

This article presents an efficient analytical workflow for protein characterization using LC–MS.

The authors continue their discussion of the role of the analysis of fragment ions in the interpretation of an analyte's mass spectrum.

In this article, the authors discuss the advantages of using a microbore UHPLC system coupled with a tandem mass spectrometer for the quantitation of in vivo pharmacokinetic samples.

The authors discuss a noninvasive method for determining early indications of the rejection of a kidney transplant.

The 57th ASMS Conference on Mass Spectrometry was held at the Pennsylvania Convention Center, 1101 Arch Street, Philadelphia, Pennsylvania, from May 31 through June 4, 2009.

The author discusses the use of high-performance mass spectrometry for small molecule and protein applications.