Other online analytical examples

Preferential crystallisation is one option for optical resolution on a manufacmr-ing scale. Online polarimetry and refractometry have been used to d3mamically optimise the process for resolution of DL-threonine in aqueous solution by variation of process parameters such as degree of supersaturation, seed quantity, initial enantiomeric excess and scale [148]. The method is claimed to be suitable for control of quasi-continuous processes. 

The application of biosensors for process monitoring has been dogged by problems with fouling, selectivity, degrading bioactivity and long-term stability. Recent developments in molecularly imprinted polymers (MIPs) show some promise as synthetic receptors and have been used for this purpose for assays and as HPLC stationary phases. Recent work has shown that MIPs show increased robustness, storage endurance and lower cost compared with biosensors, which 

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Other online HPLC techniques (such as LC-CD or LC-IR) are likely to be exploited. For example, a mixture of diastereoisomeric biflavonoids from the African plant Gnidia involucrata (Thymelaeaceae) could not be separated on a preparative scale by HPLC or crystallization. However, their analytical separation on a Cig column was sufficient to run an online LC-CD investigation and provide stereochemical information about the individual isomers. 

A major reason why XAFS spectroscopy has become a critically useful probe of catalyst structure is the fact that it is easily adapted to characterization of samples in reactive atmospheres. The X-ray photons are sufficiently penetrating that absorption by the reaction medium is minimal. Moreover, the use of X-ray- transparent windows on the catalytic reaction cell allows the structure of the catalyst to be probed at reaction temperature and pressure. For example, the catalyst may be in a reaction cell, with feed flowing over it, and normal online analytical tools (gas chromatography, residual gas analysis, Fourier transform (FT) infrared spectroscopy, or others) can be used to monitor the products while at the same time the interaction of the X-rays with the catalyst can be used to determine critical information about the electronic and geometric structure of the catalyst. 

The need for maximum sample throughput and minimal human interaction within analytical procedures has provided considerable impetus to the development of integrated systems. SPE-LC in-tube SPME followed by ultraviolet (UV) or MS detection and membrane introduction mass spectrometry (MIMS) have both been used to this end. Submersible MIMS systems capable of extended underwater deployment down to 200 m and with a mass range of up to 200 amu have recently come onto the market. Elow injection coupled with MIMS allows fast, near-real-time determination of, for example, phenols in water. Derivatization of the phenols with acetic anhydride can be used to enhance both the selectivity and sensitivity of this method. Other online derivatization procedures are under development with a view to increasing the scope for rapid determination of highly polar compounds that have previously proved difficult to analyze. Large volume injection techniques and developments in enzyme-linked immunosorbent assay (ELISA) technologies... 

The analytical strategy for a continuous process is necessarily predominantly online, as summarised in Figure 8.3. However, the correlations between continuous process development and online analysis on the one hand and batch process development and off-line analysis on the other are not simple. For example, many aspects of batch process development would benefit from the availability of online analysis and monitoring. Similarly, some of the early development stages of a continuous process will utilise data from batch (i.e. non-continuous) experiments. 

Spectroscopic detectors measure partial or complete energy absorption, energy emission, or mass spectra in real-time as analytes are separated on a chromatography column. Spectroscopic data provide the strongest evidence to support the identifications of analytes. However, depending on the spectroscopic technique, other method attributes such as sensitivity and peak area measurement accuracy may be reduced compared to some nonselective and selective detectors. The mass spectrometer and Fourier transform infrared spectrometer are examples of spectroscopic detectors used online with GC and HPLC. The diode array detector, which can measure the UV-VIS spectra of eluting analytes is a... 

Chemical databases serve different purposes, such as the search for scientific and patent-related literature or retrieval of facts about chemical compounds. In analytical chemistry, the databases that are of interest are those that contain either original measurements (spectra and chromatograms) or derived data, such as concentrations or chemical structures. These data can be retrieved online via network from a host, for example, STN International. On the other hand, databases can be stored at individual PCs or in connection with an analytical instrument. 

It is beyond the scope of the present work to discuss the different options for the analytical methods. We only present one example here, showing what can be achieved with modern instrumental analysis. Fig. 4.15 shows a NMR-spectrum of a formaldehyde + water + methanol mixture taken with an online technique with a 400 MHz NMR spectrometer. Signals from a large number of different species can be resolved. Obviously, the band assignment is non-trivial for such complex mixtures and special techniques, such as two dimensional NMR, have to be applied. One of the most attractive features of NMR spectroscopy compared with other spectroscopic methods is that the quantitative evaluation of spectra such as that shown in Fig. 4.15 can be achieved without calibration, as the area below the peaks is directly proportional to the number of the different nudei in the solution if the NMR experiment is carried out properly. 

The active site responsible for the aerobic oxidation of alcohols over Pd/AljO, catalysts has long been debated [96-lOOj. Many reports claim that the active site for this catalyst material is the metallic palladium based on electrochemical studies of these catalysts [100, 101]. On the contrary, there are reports that claim that palladium oxide is the active site for the oxidation reaction and the metalhc palladium has a lesser catalytic activity [96,97). In this section, we present examples on how in situ XAS combined with other analytical techniques such as ATR-IR, DRIFTS, and mass spectroscopic methods have been used to study the nature of the actual active site for the supported palladium catalysts for the selective aerobic oxidation of benzylic alcohols. Initially, we present examples that claim that palladium in its metallic state is the active site for this selective aerobic oxidation, followed by some recent examples where researchers have reported that ojddic palladium is the active site for this reaction. Examples where in situ spectroscopic methods have been utilized to arrive at the conclusion are presented here. For this purpose, a spectroscopic reaction cell, acting as a continuous flow reactor, has been equipped with X-ray transparent windows and then charged with the catalyst material. A liquid pump is used to feed the reactants and solvent mixture into the reaction cell, which can be heated by an oven. The reaction was monitored by a transmission flow-through IR cell. A detailed description of the experimental setup and procedure can be found elsewhere [100]. Figure 12.10 shows the obtained XAS results as well as the online product analysis by FTIR for a Pd/AljOj catalyst during the aerobic oxidation of benzyl alcohol. 

FI systems have been successfully used with spec-trophotometric detection, for example, for the determination of nitrogen and phosphorus species in rivers and streams. It has also been used to determine anionic surfactants (e.g., sodium lauryl sulfate, sodium dodecyl sulfonate), chloride, and organophos-phoric insecticides in freshwater bodies. FI also can be coupled with other analytical techniques for sample introduction purposes. Such methods include FI coupled with atomic absorption spectrometry for online preconcentration and separation of chromium species and with mass spectrometry for the determination of polar organic pollutants. 

The general requirements of process analysis will be discussed followed by the requirements and actual examples of liquid analysis, contact-type solid analysis, and noncontact sample arrangement. The spectroscopic and mathematical principles of NIR online analysis are similar to those discussed in the other chapters of this book. The emphasis of this discussion will be on the specific instrumental requirements and special sampling requirements that are unique to the process analytical approach. 

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