Thermally labile samples

The requirement for volatility often precluded the use of GC for analysis of thermally labile samples. Injection of the sample directly into the column using cool-on-column injection (COC) with volatilisation occurring on the column has meant such samples can be readily analysed [73a,b]. 

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For nonvolatile or thermally labile samples, a solution of the substance to be examined is applied to the emitter electrode by means of a microsyringe outside the ion source. After evaporation of the solvent, the emitter is put into the ion source and the ionizing voltage is applied. By this means, thermally labile substances, such as peptides, sugars, nucleosides, and so on, can be examined easily and provide excellent molecular mass information. Although still FI, this last ionization is referred to specifically as field desorption (FD). A comparison of FI and FD spectra of D-glucose is shown in Figure 5.6. 

Cool on-column Liquid sample is directly and totally passed from syringe into column or its extension. Cold injection followed by temperature program Dilute, thermally labile samples high-boiling components Fair, some focusing required 0.1-1 100... 

The mobile phase in LC-MS may play several roles active carrier (to be removed prior to MS), transfer medium (for nonvolatile and/or thermally labile analytes from the liquid to the gas state), or essential constituent (analyte ionisation). As LC is often selected for the separation of involatile and thermally labile samples, ionisation methods different from those predominantly used in GC-MS are required. Only a few of the ionisation methods originally developed in MS, notably El and Cl, have found application in LC-MS, whereas other methods have been modified (e.g. FAB, PI) or remained incompatible (e.g. FD). Other ionisation methods (TSP, ESI, APCI, SSI) have even emerged in close relationship to LC-MS interfacing. With these methods, ion formation is achieved within the LC-MS interface, i.e. during the liquid- to gas-phase transition process. LC-MS ionisation processes involve either gas-phase ionisation (El), gas-phase chemical reactions (Cl, APCI) or ion evaporation (TSP, ESP, SSI). Van Baar [519] has reviewed ionisation methods (TSP, APCI, ESI and CF-FAB) in LC-MS. 

Volatile or volatilizable compounds may be introduced into the spectrometer via a pinhole aperture or molecular leak which allows a steady stream of sample molecules into the ionization area. Non-volatile or thermally labile samples are introduced directly by means of an electrically heated probe inserted through a vacuum lock. Numerous methods of sample ionization are available of which the most important are electron impact (El), chemical ionization (CY), field ionization (FI), field desorption (FD), fast atom bombardment (FAB), and radio-frequency spark discharge. 

The most common job for these systems is the fast-running isocratic separation. They could be built up from the QC isocratic, but dial-a-mix isocratic is faster and more convenient since they switch easily from job to job. These systems come in the same two flavors as the research gradient, low- and high-pressure mixing, but replace the manual injector with an autosampler, allowing 24-hr operation. For thermally labile samples that need to be held for a period of time before being injected, there are autosampler chillers available. 

In recent years, several techniques have been developed for mass spectrometry, whereby samples are ionized and analysed from a condensed phase, without prior volatilization. These desorption techniques have permitted the extension of mass spectrometric analyses to sulfate and glutathione conjugates, as well as to underivatized and labile glucuronic acid conjugates. Primary among these techniques are field desorption 6, plasma desorption (7), laser desorption (8), fast atom bombardment (or secondary ion mass spectrometry with a liquid sample matrix) ( ) and thermospray ionization ( O). The latter can also serve to couple high pressure liquid chromatography and mass spectrometry for analysis of involatile and thermally labile samples. 

Electron impact (El), the method outlined in Section 9.6.1, is the conventional method of ionizing samples for MS. However, El is not free from disadvantages, such as inability to provide molecular weight information from thermally labile samples, difficulty for study of low-volatility materials, complex spectra arising from interference between molecular and fragment ions, etc. In order to overcome these problems, a large number of alternative ionization methods, collectively known as soft ionization methods have been developed. Reviews of the available techniques have been compiled by Milne and Lacey (1974) and Games (1978). Chemical ionization (Cl), field ionization (FI) and field desorption (FD)... 

One of the major problems in analytical chemistry is the detection and identification of non-volatile compounds at low concentration levels. Mass spectrometry is widely used in the analysis of such compounds, providing an exact mass, and hence species identification. However, successful and unequivocal identification, and quantitative detection, relies on volatilization of the compound into the gas phase prior to injection into the analyser. This constimtes a major problem for thermally labile samples, as they rapidly decompose upon heating. In order to circumvent this difficulty, a wide range of techniques have been developed and applied to the analysis of nonvolatile species, including fast atom bombardment (FAB), field desorption (FD), laser desorption (LD), plasma desorption mass spectrometry (PDMS) and secondary-ion mass spectrometry (SIMS). Separating the steps of desorption and ionization can provide an important advantage, as it allows both processes to be... 

After its introduction, GC developed at a phenomenal rate, growing from a simple research novelty to a highly sophisticated instrument. Moreover, the current-day requirements for high resolution and trace analysis are satis ed by modern column technology. In particular, inert, thermostable, and ef dent open-tubular columns are available, along with associated selective detectors and injection methods, which allow on-column injection of liquid and thermally labile samples. The development of robust fused-silica columns, characterized by superior performances to that of glass columns, brings open-tubular GC columns within the scope of almost every analytical laboratory. 

Analysis. The flow reverses in the cold trap and the trap tube is rapidly heated at a rate of up to 100,000°C/s. Because the sample is trapped and injected from the same end of the trap, it is in the heated metal trap tube for a minimal period of time. This reduces the possibility of decomposition of thermally labile samples. Broadening from the dead volume of the tube itself is also reduced. 

LC - MS type LC flow range Detection limit Solvent type range Nonvolatile thermally labile samples Semivolatile samples Molecular mass range... 

Nonvolatile Sample Molecules For nortvolatile or thermally labile sample molecules, a variety of ionization methods have been developed over the past 50 years. 

The first measurements of molecules that were involved during thermogravimetric analysis were reported by Lephardt and Fenner [50,51], who showed the time evolution of several gases that are evolved when tobacco or other thermally labile samples are heated. Despite the obvious information that this experiment yielded and the simplicity of the apparatus, it took several years for instrument companies to introduce a commercial TGA/FT-IR interface. The gas cell installed in these systems is much... 

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