Coupling of instrumentation

Over time, a large number of traditional laboratory instruments have been morphed to meet industrial needs for QC applications. Example applications include raw material, product QC and also some environmental testing. In such scenarios laboratory instruments appear to work adequately. Having said that, there are issues the need for immediate feedback and the need for smaller, cheaper, and more portable measurements. There is a growing interest in the ability to make measurements in almost any area of a process, with the idea that better production control can lead to a better control of the process and of the quality of the final product. The cost of implementation of today s (2004) process analyzers is still too high, and it is impractical to implement more than a couple of instruments on a production line. Also, there is growing concern about the operating environment, worker safety, and environmental controls. 

The future of the pharmaceutical industry rests on the ability to discover and develop new molecules into products. The faster that information can be delivered to product managers and regulatory scientists, the greater the potential for shortening the time to market. Consequently, there is an economic pressure to devise instruments able to deliver many data sets at once. Coupling of instruments has become easier with expanded capabilities (HPLC-DAD-MS is almost routine, HPLC-DAD-NMR-MS is now a common commercial instrument). 

The site was a drained marsh which received no artificial N inputs, although cattle were present on the site until a couple of weeks before the experiment. NjO emissions were measured by chamber techniques as no instrumental techniques were sensitive enough at that stage to permit micrometeorological measurements. Although spatially very variable, the mean emission rate from the site was 4ng NjO-Nm s h The sporadic measurements made impossible the determination of any response to temperature or water status. 

The great advance in the field of instrumentation, coupled with the discovery of the heterogeneity of the pyrethrolone radical, has advanced the knowledge of pyrethrum chemistry considerably beyond that known in 1945. LaForge and Barthel (24,25) have shown the structure of the active ingredients of pyrethrum, known collectively as pyrethrins, to be esters as represented by the structure shown in Table I. 

The advantages of controlled-potential techniques include high sensitivity, selectivity towards electroactive species, a wide linear range, portable and low-cost instrumentation, speciation capability, and a wide range of electrodes that allow assays of unusual environments. Several properties of these techniques are summarized in Table 1-1. Extremely low (nanomolar) detection limits can be achieved with very small sample volumes (5-20 pi), thus allowing the determination of analyte amounts of 10 13 to 10 15 mol on a routine basis. Improved selectivity may be achieved via the coupling of controlled-potential schemes with chromatographic or optical procedures. 

The first example of microwave-promoted solid-phase methodology in heterocyclic chemistry was the arylation of thiophene and indole via Suzuki couplings on TentaGel S RAM resin, as demonstrated by Hallberg and coworkers in 1996, before temperature- and pressure-controlled microwave instruments were even available [189]. Three years later Schotten and coworkers presented analogous but aqueous Suzuki couplings of 5-bromo-thiophene anchored to PEG soluble support via a carboxylic function at its C-2 position [116]. Unfortunately, this work was performed in a do-... 

The on-line principle has also been extended into the field of detection (Fig. 8). Thus, it is now possible to record FTIR [27-31] and Raman spectra in situ [32, 33], and there have been considerable advances in the on-line coupling of thin-layer chromatography with mass spectrometry. Here it has been, above all, the research groups of Wilson [34-36] and Busch [37-40] that have made the necessary instrumental and methodological advances, so that TLC must no longer be viewed as merely a clean-up method. Rather it forms the essential central point for all these on-line coupling techniques. 

Chromatographic systems were finally coupled with relatively inexpensive, yet powerful, detection systems with the advent of the quadrupole mass selective detector (MSD). The operational complexity of this type of instrumentation has significantly declined over the last 15 years, thus allowing routine laboratory use. These instruments... 

On-line SFE-SFC modes present several distinct advantages that are beyond reach of either technique when used separately (Table 7.13). An obvious advantage of SFE is that it is an ideal way to introduce a sample into an SFC system. Because the injection-solvent is the same as the mobile phase, in this respect the criteria for a successful coupling of different techniques are fulfilled [94], i.e. the output characteristics from the first instrument and the input characteristics of the second instrument are compatible. Supercritical fluid techniques can separate high-MW compounds are significantly faster than classical Soxhlet extractions and require less heat and solvent. SFE-SFC techniques are versatile,... 

LC-PB-MS is especially suited to NPLC systems. RPLC-PB-MS is limited to low-MW (<500 Da) additives. For higher masses, LC-API-MS (combined with tandem MS and the development of a specific mass library) is necessary. Coupling of LC via the particle-beam interface to QMS, QITMS and magnetic-sector instruments has been reported. In spite of the compatibility of PB-MS with conventional-size LC, microbore column (i.d. 1-2 mm) LC-PB-MS has also been developed. A well-optimised PB interface can provide a detection limit in the ng range for a full scan mode, and may be improved to pg for SIM analyses. 

Raman microscopy has been used for analysis of very small samples or small heterogeneities in larger samples. Recent developments and applications of this technique have been reviewed by Turrell and Corset (1996), including a discussion of the coupling of Raman microscopy with electron, ion and x-ray microscopies, and these authors give a description of a number of prototype instruments with this facility. 

A direct combination of separation and analysis techniques is thus invaluable. GLC-MS and HPLC-MS coupling are now routinely used. Because of the high sensitivity of modern NMR instruments the coupling of HPLC and NMR is now used in many NMR laboratories, and we shall discuss the principles... 

MSn are of particular interest. MSn stands for the n-fold coupling of mass spectrometers, alternatively serving as separation and detection instrument. By hyphenated techniques the dimensionality of analytical information (see Sect. 3.4) and, therefore, also the information amount (see Sect. 9.3) is significantly increased (Eckschlager and Danzer [1994]). 

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