Sensitivity of mass spectrometers

The preponderance of analytical (and preparative) separations that precede mass spectrometric analyses are carried out using HPLC. Despite its potential for extremely high efficiencies, capillary electrophoresis (CE) remains something of a specialized application, particularly with mass spectrometric detection. The technique is hampered by its reliance on small sample volumes (typically nL injections) in order to avoid loss of separation efficiency. The consequence of these small volumes is a concentration detection limit that is substantially higher than that of techniques such as HPLC. Despite the exquisite sensitivity of mass spectrometers, characterization of related substances present at low femtomole levels (assuming a hypothetical related substance compound with molecular weight 500 daltons present at 0.1% w/w in an equally hypothetical drug substance sample... 

An impetus in the field of mass spectrometry (MS) analysis occurred in the early 1990s with the invention of two novel and soft ionization methods, electrospray ionization (ESI) by John Fenn and matrix-assisted laser desorption ionization (MALDI) by Koichi Tanaka, who both shared the Nobel Prize in Chemistry in 2002. A second impetus, which is more diffuse, is currently occurring and consists of miniaturization. Whereas the intrinsic sensitivity of mass spectrometers has roughly remained the same for a couple of decades, the amount of material required for recording one spectrum has... 

Fatty Acid Methyl Ester (FAME) Detection The unique fatty acid composition and variability of the relative abundances of these species among microorganisms from different genera have been summarized as early as half a century ago by O Leary (1962). Subsequent developments in increasing sensitivity of mass spectrometers obviated the need for analysis of these nonvolatile, highly abundant compounds for biodefense approaches. Laboratory protocols have been developed to optimize the esterification procedure to increase the yield and minimize the required reaction time. 

Many liquid phases for packed-column purposes were unacceptable for capillary GC. Although they offered selectivity, overriding factors responsible for their disfavor were overall lack of thermal stability and the instability of the stationary phase as a thin film at elevated temperatures and during temperature programming. In the latter processes, it is crucial that the phase remain a thin uniform film otherwise, loss of both inermess and column efficiency result. Today, these problems have been solved and the refinements are reflected in the high performance of commercial columns. The impetus has been driven by the improvements in the sensitivity of mass spectrometers such that the MS detector is now the second most popular detector in GC (the FID is the most widely used detector). This rise in the use of GCMS has also necessitated more thermally stabile columns offering much less column bleed. 

Stable isotope dilution mass-spectrometry (MSID) is the most accurate technique for determining lanthanide abundances in geochemical materials.. The superior quality of the method may be attributed principally to the inherent sensitivity of mass-spectrometers, and to the use of the ideal internal standard, namely, an artificially enriched isotope of each element to be determined. The utilization of isotopic internal standards virtually eliminates such potential analytical problems as quantitative recovery and instrument calibration. The sensitivity of the mass spectrometer is such that the lower limit of measurable abundance is usually controlled by the purity of the reagents used in preparing the sample for analysis. 

Different combinations of stable xenon isotopes have been sealed into each of the fuel elements in fission reactors as tags so that should one of the elements later develop a leak, it could be identified by analyzing the xenon isotope pattern in the reactor s cover gas (4). Historically, the sensitive helium mass spectrometer devices for leak detection were developed as a cmcial part of building the gas-diffusion plant for uranium isotope separation at Oak Ridge, Tennessee (129), and heHum leak detection equipment is stiU an essential tool ia auclear technology (see Diffusion separation methods). 

Such techniques imply analysis of chemical products of photolysis. Application of mass-spectrometers of various types is often hampered by a number of circumstances. These difficulties will be discussed later on. The EPR method, which is currently the most extensively employed technique, features low sensitivity and is usually used for analysis of primary fragments of photolysis. For this purpose, the radicals produced are frozen on the walls of a quartz pin and are thus accumulated inside the device. On one hand, this approach allows one to overcome the sensitivity threshold of the device. However, on the other hand, this excludes the possibility of direct kinetic measurements. The SS technique permits the use of weak light sources for detecting active particles under... 

In a well-equipped laboratory it is mandatory that these three techniques be coupled with a mass spectrometric detector in order to achieve a combination of resolution of mixtures, positive identification of separated organics and the high sensitivity that is essential when dealing with environmental samples. The penetration of mass spectrometers in recent years is indicated by the fact that of the 50 types of organic compound that have been determined by gas chromatography in 21 cases mass spectrometric detection is discussed. This trend will, no doubt, continue. 

The coupling of a mass spectrometer to CE and CEC provides a powerful system for the analysis of pharmaceuticals and complex biological mixtures. This can replace or complement other conventional detection methods such as UV, electrochemical, or LIE that provide less structural information. The use of mass spectrometer as a detector enhances the usefulness of the CE and CEC and allows an efficient separation and identification of complex mixtures, obtaining structure and/or molecular mass information. The choice of mass analyzers used in CE/CEC-MS depends on factors such as sensitivity, mass resolution, requirement for structural elucidation, and the type of application (Table 5). The analyzers that have been used in CEC analysis include time-of-flight (TOE), quadrupole (Q), ion-trap (IT), fourier... 

As we optimized Tethering we used a variety of mass spectrometers. In our experience, the sensitivity and high resolution of TOP analyzers has provided the most rapid and accurate analyses of intact proteins. An example of an ESI-TOF data set from a standard experiment is illustrated in Fig. 9.2. Figure 9.2A is the deconvoluted mass spectrum of a Cys-mutant target protein after equilibration... 

The detection of a test gas using mass spectrometers is far and away the most sensitive leak detection method and the one most widely used in industry. The MS leak detectors developed for this purpose make possible quantitative measurement of leak rates in a range extending aaoss many powers of ten (see Section 5.2) whereby the lower limit = 10 mbar l/s, thus making it possible to demonstrate the inherent gas permeability of solids where helium is used as the test gas. It is actually possible in principle to detect all gases using mass spectrometry. Of all the available options, the use of helium as a tracer gas has proved to be especially practical. The detection of helium using the mass spectrometer is absolutely ( ) unequivocal. Helium is chemically inert, non-explosive, non-toxic, is present in normal air in a concentration of only 5 ppm and is quite economical. Two types of mass spectrometer are used in commercially available MSLD s ... 

TOF mass spectrometers are among the most sensitive of mass analysers and can operate up to very high molecular masses (very low velocities). 

Inductively coupled plasma-mass spectrometry (ICP-MS) is revolutionizing the measurements of refractory metals, such as titanium, and can provide a wealth of isotopic information that could only be obtained previously with great difficulty. ICP-MS has been used as a fast and sensitive technique for measuring 230Th in marine sediments (Shaw and Francis, 1991) and barium in seawater (Klinkhammer and Chan, 1990). For the future, advances in the capabilities of mass spectrometers can be expected (Table 4), developed by interdisciplinary groups of academic, government, and industry scientists. It is unlikely, though not impossible, that MS techniques will be appropriate for buoy development. 

The advent of the use of mass spectrometers as detectors and new mass detectors such as the charged aerosol detectors (CAD) and evaporative light scattering detectors (ELSD) should provide high-sensitivity detection of compounds that do not absorb UV light. The only problem with most of these is that they are expensive and, therefore, not readily available. When prices come down, they should finally eliminate the use of derivatives in HPLC analysis. 

Developments in mass spectrometry technology, together with the availability of extensive DNA and protein sequence databases and software tools for data mining, has made possible rapid and sensitive mass spectrometry-based procedures for protein identification. Two basic types of mass spectrometers are commonly used for this purpose Matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF) mass spectrometry (MS) and electrospray ionization (ESI)-MS. MALDI-TOF instruments are now quite common in biochemistry laboratories and are very simple to use, requiring no special training. ESI instruments, usually coupled to capillary/nanoLC systems, are more complex and require expert operators. We will therefore focus on the use of MALDI-... 

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