At-line

Figure 8. Tomographic horizontal cuts of the 3D voxel array of object no. 2, at line 20 (a), 50 (b) and 80 (c).

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). 

The degree of drying desired will vary with the pneumatic equipment and application involved. The aim is to eliminate further condensation in the airlines and pneumatic tools or devices. Prevailing atmospheric conditions also have an influence on the approach that is most effective. In many 100-psig installations, a dew point at line pressure of from 500°F to 350°F is adequate. Other applications, such as instrument air systems, will require dew points of minus 500°F. 

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). 

Fig.1 Schematic representation of the different nucleation sites on the alumina film Mid nucleation at line defects, Mpd nucleation at point defects, Mrs nucleation at regular surface sites...

The nucleation behavior of transition metal particles is determined by the ratio between the thermal energy of the diffusing atoms and the interaction of the metal atoms at the various nucleation sites. To create very small particles or even single atoms, low temperatures and metal exposures have to be used. The metal was deposited as metal atoms impinging on the surface. The metal exposure is given as the thickness (in monolayer ML) of a hypothetical, uniform, close-packed metal layer. The interaction strength of the metals discussed here was found to rise in the series from Pd < Rh < Co ( Ir) < V [17,32]. Whereas Pd and Rh nucleate preferentially at line defects at 300 K and decorate the point defects at 90 K, point defects are the predominant nucleation center for Co and V at 300 K. At 60 K, Rh nucleates at surface sites between point defects [16,33]. 

It is remarkable that the feature at 2097 cm which was observed for a preparation at 90 K is missing at 60 K. The peak shows the characteristics of a monocarbonyl in mixing experiments. Furthermore, thermal treatment of the deposit as shown in Fig. 3a reveals a slightly increased thermal stability of this species as compared to the dicarbonyl at point defects. From this information it was suggested that the monocarbonyl is located at line defects of the alumina film [15]. 

By default, Import entire file is selected, so deselect it and specify that line 1 is to be used for column headings and that all rows at line 2 and beyond are to be imported. Next, select the Text Format option and make the following changes so that the pipe character is set as the variable delimiter. 

Other forms of analytical investigations may also be applied, such as at-line analysis (discontinuous direct analysis of objects, e.g., noninvasive blood glucose monitoring) and trans-line analysis (remote sensing, teleanalysis). 

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. 

Some of the earliest work on NIR of bioprocesses was performed on the nutrients and metabolites in a fermentation broth. A classic paper (if 1996 is antiquity) was written by Hall et al.30 on the determination of acetate, ammonia, biomass, and glycerol in E. coli fermentations. This early paper used NIR to simultaneously monitor all the above-mentioned parameters. The correlation coefficients were all better than 0.985 with variable SEPs acetate, 0.7 g/1 ammonia, 7 mM glycerol, 0.7 g/1 and biomass, 1.4 g/1. While later work with more modem equipment has attained better results, this remains as one of the first. The work was performed at line in a cuvette, but rapidly enough to be considered a process measurement. 

Having seen the number of papers devoted to bioprocess analyses utilizing vibrational spectroscopy, it cannot be considered an experimental tool any longer. Manufacturers are responding to pressure to make their instruments smaller, faster, explosion-proof, lighter, less expensive, and, in many cases, wireless. Processes may be followed in-line, at-line, or near-line by a variety of instruments, ranging from inexpensive filter-based to robust FT instruments. Raman, IR, and NIR are no longer just subjects of feasibility studies they are ready to be used in full-scale production. 

Hammond, S.V. and Brookes, I.K., Near infrared spectroscopy — a powerful technique for at-line and on-line analysis of fermentations, Harnessing Biotechnology for the 21st Century Proceedings of the 9th International Biotechnology Symposium Exposition, Eds Ladisch, M.R. and Bose, A., pp. 325-333. American Chemical Society, Washington, D.C. (1992). 

Typically, this definition is accompanied by the characterization of the measurement relative to the process as in-line (probe in direct contact with the sample inside the processing equipment), on-line (the sample is withdrawn from process via a sampling loop probe not directly part of processing equipment) and at-line (the sample is removed from process but measured in close proximity to process, within the timescale of processing). 

Instrnmentation for UV-vis process analysis falls into fonr categories scanning instruments, diode-array instrnments, photometers, and fiber-optic spectrophotometers with photodiode-array (PDA) and charge-conpled device (CCD) detectors. The former two are more typically enconntered in at-line or near-line applications, whereas the latter two are better snited to actnal on-line analyses. 

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