At-line sampling

At-line sampling may involve a flow-through cell in the NIR spectrometer in one process a glass-lined steel reaction vessel was used in combination with a fibre optic probe for measurements in a full scale chemical plant reactor [57]. Fibre optic bundles can be used to transmit NIR radiation to the reaction matrix and take signal back to the spectrometer. NIR is notoriously sensitive to changes in temperature and methods for keeping the temperature constant must be incorporated into the instrumentation. 

Additionally, near-infirared spectroscopy has been utilized to monitor moisture for endpoint determination (155,156), though this technique is limited to detecting only moisture at the bed surface. The FBRM is a technique for panicle size determination in a study by Dilworth et al. (157), comparing power consumption. FBRM, and acoustic signals, these measurements were found to be complimentary. Thermal effusivity is a material propeny that combines thermal conductivity, density and heat capacity. Fariss et al. (158) used at-line samples and found colinearity between power consumption and thermal effusivity. 

In summary, with carefully designed at-line sample preparation-GC systems, analyte detectability can be made similar to that in on-line SPE-GC setups. However, interferences due to contamination and analyte losses will always be more serious. 

With a special optical system at the sample chamber, combined with an imagir system at the detector end, it is possible to construct two-dimensional images of the sample displayed in the emission of a selected Raman line. By imaging from their characteristic Raman lines, it is possible to map individual phases in the multiphase sample however, Raman images, unlike SEM and electron microprobe images, have not proved sufficiently useful to justify the substantial cost of imaging optical systems. 

Figure 11.16 Chromatograms of plasma samples obtained by using SPE-SFC with super-aitical desorption of the SPE cartridge (a) blank plasma (20 p.1), UV detection at 215 nm (b) blank plasma (20 p.1), UV detection at 360 nm (c) plasma (1 ml) containing 20 ng mitomycin C (MMC), UV detection at 360 nm. Reprinted from Journal of Chromatography, 454, W. M. A. Niessen et al., Phase-system switching as an on-line sample pretreatment in the bioanalysis of mitomycin C using supercritical fluid cliromatography, pp. 243-251, copyright 1988, with permission from Elsevier Science.

Electropherograms of a urine sample (8 ml) spiked with non-steroidal anti-inflammatory drugs (10 p-g/ml each) after direct CE analysis (b) and at-line SPE-CE (c). Peak identification is as follows I, ibuprofen N, naproxen K, ketoprofen P, flurbiprofen. Reprinted from Journal of Chromatography, 6 719, J. R. Veraait et al., At-line solid-phase exti action for capillary electrophoresis application to negatively charged solutes, pp. 199-208, copyright 1998, with permission from Elsevier Science. 

J. R. Veraait, C. Gooijer, H. Lingeman, N. H. Velthorst and U. A. Th Brinkman, At-line solid-phase exti action coupled to capillary electi ophoresis deteitnination of amphoteric compounds in biological samples , 7. High Resolut. Chromatogr. 22 183-187(1999). 

Attenuation of the analytical lines could be counterbalanced by increased line intensity at the sample. For a sample of greater than critical thickness, high intensity in an analytical line is favored by... 

It is preferable to sample vertical pipelines rather than horizontal lines (ideally when the flow of steam is downward rather than rising). Sampling in the vicinity of bends, elbows, and valves should be avoided. At the sample point, the multiport valve should be installed perpendicular to the flow of steam. 

Chromatography. GC is the most common anal)d ical method used but liquid and supercritical fluid chromatographic methods are being increasingly developed. Like titration the sample is destroyed in the analysis process. The ideal situation depicted in Figure 8.8 cannot normally be applied for titration or chromatographic analysis since the analysis equipment needs to be close to the sampling device. This is often termed at-line analysis. 

Determination of appropriate measuring and analysis methods. Decisions must be made on the selection of appropriate and available measuring and or analytical equipment and tools. The characteristics of the methods must be discussed in terms of specificity, accuracy, precision, sensitivity of the methods, and locations of measuring and/or sampling (off-line, at-line, on-line, in-line, non-invasive). 

In Raman measurements [57], the 514-nm line of an Ar+ laser, the 325-nm line of a He-Cd laser, and the 244-nm line of an intracavity frequency-doubled Ar+ laser were employed. The incident laser beam was directed onto the sample surface under the back-scattering geometry, and the samples were kept at room temperature. In the 514-nm excitation, the scattered light was collected and dispersed in a SPEX 1403 double monochromator and detected with a photomultiplier. The laser output power was 300 mW. In the 325- and 244-nm excitations, the scattered light was collected with fused silica optics and was analyzed with a UV-enhanced CCD camera, using a Renishaw micro-Raman system 1000 spectrometer modified for use at 325 and 244 nm, respectively. A laser output of 10 mW was used, which resulted in an incident power at the sample of approximately 1.5 mW. The spectral resolution was approximately 2 cm k That no photoalteration of the samples occurred during the UV laser irradiation was ensured by confirming that the visible Raman spectra were unaltered after the UV Raman measurements. 

On-line sample-stacking techniques " and, more recently, the use of isotacho-phoresis have added to the potential benefits of CE by permitting the concentration of analyte in a large volume by exploiting the difference in the electric field between the dilute sample and system buffer. The electric field is much stronger in the dilute buffer-sample and hence analyte ions move faster until they reach the border with the separation buffer. At this point they slow down, causing the analyte to concentrate as a sharp sample band at the interface. 

Miniaturisation of SPE has also been described [504]. Thurman and Mills [508] discussed the history and future of SPE. The technique will continue to replace LLE. More on-line use of both LC and GC are prospected. As instruments such as GC-MS and HPLC-MS become more sensitive, smaller sample sizes may be used. New phases will continue to be introduced to take full advantage of specific interactions. It is expected that at last sample handling and SPE will reach the level of sophistication that its relatives in LC have reached, and perhaps go beyond. 

Mass spectrometry can be specific in certain cases, and would even allow on-line QA in the isotope dilution mode. MS of molecular ions is seldom used in speciation analysis. API-MS allows compound-specific information to be obtained. APCI-MS offers the unique possibility of having an element- and compound-specific detector. A drawback is the limited sensitivity of APCI-MS in the element-specific detection mode. This can be overcome by use of on-line sample enrichment, e.g. SPE-HPLC-MS. The capabilities of ESI-MS for metal speciation have been critically assessed [546], Use of ESI-MS in metal speciation is growing. Houk [547] has emphasised that neither ICP-MS (elemental information) nor ESI-MS (molecular information) alone are adequate for identification of unknown elemental species at trace levels in complex mixtures. Consequently, a plea was made for simultaneous use of these two types of ion source on the same liquid chromatographic effluent. 

Clearly, the potential applications for vibrational spectroscopy techniques in the pharmaceutical sciences are broad, particularly with the advent of Fourier transform instrumentation at competitive prices. Numerous sampling accessories are currently available for IR and Raman analysis of virtually any type of sample. In addition, new sampling devices are rapidly being developed for at-line and on-line applications. In conjunction with the numerous other physical analytical techniques presented within this volume, the physical characterization of a pharmaceutical solid is not complete without vibrational analysis. 

With the advance of computer techniques, especially implementation of distributed control systems (DCS) to chemical processes, a large set of on-line measurements are available at every sampling period. The rational use of this large volume of data requires the application of suitable techniques to improve their accuracy. This goal has triggered the focus on research and development, during the last ten years, in the area of plant data reconciliation. Complete reviews on the subject can be found in the works of Mah (1990), Madron (1992), and Crowe (1996). 

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