LC effluents

Liquid samples are generally nebulized and the resulting aerosols are injected into the axial channel of the ICP (Fig. 5.1). A pneumatic nebulizer, such as the concentric lype shown in Fig. 5.4, is commonly used. The nebulizer is usually mounted inside a spray chamber, which prevents large droplets from reaching the plasma. In ICP-MS, the outer wall of the spray chamber is often cooled to remove as much solvent as possible [14, 15]. Removal of solvent is particularly desirable when an organic modifier is used for the separation, as described below. 

Roughly 1% to 3% of the sample flow into the nebulizer actually reaches the plasma. Fortunately, the ICP-MS device has the powers of detection to compensate for this inefficiency. The nebulizer is content with sample flow rates in the range 0.3-3 ml min . If the spray chamber outlet is connected directly to the base of the torch, as is common, the ion signal from a fresh sample can be observed roughly 3 s after the sample reaches the tip of the nebulizer. 

The LC-ICP-MS experiments in the authors laboratory have employed an ultrasonic nebulizer, which is roughly 10% efficient [20, 21] but has a substantial dead volume in the gas phase. When the technique progresses to the use of better separations of more complex mixtures, sample introduction devices with less opportunity for broadening, such as the direct injection nebulizer [22, 23], may become necessary. 

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One of the earliest models is illustrated in Figure 13.3, which clearly shows the principles used in later improvements. The LC effluent was pumped along a length of silica capillary tubing inside... 

Applications Rather intractable samples, such as organic polymers, are well suited to FD, which avoids the need for volatilisation of the sample. Since molecular ions are normally the only prominent ions formed in the FD mode of analysis, FD-MS can be a very powerful tool for the characterisation of polymer chemical mixtures. Application areas in which FD-MS has played a role in the characterisation of polymer chemicals in industry include chemical identification (molecular weight and structure determination) direct detection of components in mixtures off-line identification of LC effluents characterisation of polymer blooms and extracts and identification of polymer chemical degradation products. For many of these applications, the samples to be analysed are very complex... 

FIGURE 5.9 The flow gating interface from Hooker and Jorgenson (1997). The cross-flow of buffer prevents LC effluent from electromigrating onto the CE capillary until an injection is desired. This figure is used by permission of the American Chemical Society. 

FIGURE 16.6 Schematic of the clear flow gating interface. The interface was constructed in-house from a 1 in. diameter, 0.5 in. thick Lexan disk. The disk is clear, which allows direct observation of the capillaries in the stream of flush buffer. The capillaries are sleeved in 0.0625 in. o.d. Teflon tubing and this tubing is held in place by Lite Touch fittings (not shown). The cross-flow of buffer prevents LC effluent from electromigrating onto the CZE capillary until an injection is desired (reprinted with permission from Analytical Chemistry). 

For plasma and blood experiments, LC effluent was directed to waste for the first 1 min. Conventional blood analysis by drawing 1 mL samples from the saphenous catheter was used to validate SPME results. These samples were subjected to PPT with acetonitrile and the supernatant from centrifugation was analyzed. The SPME probes were also evaluated for pharmacokinetic analysis of diazepam and its metabolites, oxazepam and nordiazepam. Good correlation was obtained for conventional blood drawn from saphenous and cephalic sites of the animals, as shown in Figure 1.48. Although the analytical parameters for the automated study need improvement, the authors cite the study as a first demonstration of SPME technology for in vivo analysis. 

One problem with GC-MS, in addition to being labor intensive and having particularly long analysis times, was that higher molecular weight (molar mass) components or compounds with preformed cations (such as cholines or carnitine) are easily hydrolyzed and cannot be analyzed effectively using GC-MS. With the advent of new ionization techniques for LC effluents (see Section 4.1.2), such as electrospray ionization (see Section 2.1.15), more volatile and larger molecular mass compounds could be analyzed,... 

Coupling of liquid chromatography to mass spectrometry has not only led to a wide variety of interfaces, but also initiated the development of new ionization methods. [8-13,62] In retrospect, the moving belt interface seems rather a curiosity than a LC-interface. The LC effluent is deposited onto a metal wire or belt which is heated thereafter to desolvate the sample. Then, the belt traverses a region of... 

Significantly lower detection limits were reported by other workers who described an LC-ESP-MS confirmatory procedure for the simultaneous determination of five penicillins in milk and meat (108). Using highly sophisticated instrumentation, all the LC effluent could be provided for the ESP-MS in this way, limitations, such as the low flow rate and the use of a postcolumn splitter, tliat restricted the practicability of the previous method could be overcome. Acquisition of penicillin signals was canned out under SIM conditions in the negative-ion mode. 

Non-Stop-Flow Mode In the non-stop-flow mode, the LC-ARC system is operated in a similar manner to the conventional continuous-flow analysis. If a mass spectrometer is coupled to the LC-ARC system, the LC effluent is split postcolumn to deliver a fraction to the radiochemical detector and the balance to a mass spectrometer. 

Successful transfer of large volumes of liquid chromatography (LC) effluent to GC requires that the solvent must be evaporated some place in the inlet system. The two most common approaches to the evaporation are the retention gap and concurrent solvent evaporation. In concurrent solvent evaporation, the column oven is kept above the boiling point of the LC solvent. Using a valve-loop interface, LC effluent up to several milliliters is driven by the carrier gas into a precolumn. In this case, the eluent evapo-... 

In the off-line approach, analyte and matrix depositiorr are decoupled from MS analysis and only instrument-specific plate formats have to be considered in interface design. In this case interface design focuses on the development of techniques for a perfect transfer of LC-effluent and matrix to the surface from which laser desorption takes place at a later stage. The development of suitable techniques started very early in conjunction with capillary electrophoresis (CE) and some of the methods which are applied nowadays for low-flow LC-MALDI are included in the following compilation. 

A continuous-flow post-colunm ligand-exchange reaction of phosphopeptides with fluorescent Fe " -methylcalcein blue (MCB) coupled to ESI-MS has been proposed as alternative means to selectively detect phosphopeptides in tryptic digests [45]. The system detects the presence of a phosphopeptide in the LC effluent as a peak in the MCB reporter trace, measured by SIM. Because not all phosphopeptide reacts with Fe, the free phosphopeptide can be simultaneously characterized by MS or MS-MS. Using conventional-flow ESI-MS (100 pl/min), detection hmits were 2 pmol/pl. 

In order to minimize the mass spectrometer source contamination from residue analysis and to prevent clogging the LC/MS vaporizer tip we vent the LC effluent for the first 5 min. The effluent is switched back to the mass spectrometer at least 5 min before the first peak elutes to allow equilibration of the ionization process and maintain reproducibility. 

The new Thermospray "Universal Interface" was been developed to allow HPLC to be properly coupled to conventional El and Cl mass spectrometry. A block diagram of the new interface is shown in Figure 1. The LC effluent is directly coupled to a Thermospray vaporizer in which most, but not all, of the solvent is vaporized and the remaining unvaporized material is carried along as an aerosol in the high velocity vapor jet which is produced. The operation and control of the thermospray device has been described in detail elsewhere. (1)... 

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