Online analysis and automation

Miniaturized near-infrared sensors were developed and implemented for online analysis and automated process control to also meet the safety requirements for handling of ozone and halogenating agents [49,50]. A target is to reduce the time from process idea to production (time-to-market) as well as development costs and costs for installation of the production unit. As pharmaceutical industry relies on the manufacture of many different products on smaller scale, and intermediates in quantities ranging from some kilograms to tons per year a modular approach toward a multipurpose microreactor plant is demanded. 

Carryover. If the automated method is coupled with online HPLC analysis and carryover is observed from one sample to the next, the HPLC injector must be considered as a potential source of carryover. Normally, if carryover is observed,... 

Reversed-phase HPLC is widely utilized to generate a peptide map from digested protein, and the MS online method provides rapid identification of the molecular mass of peptides. The HPLC-MS-FAB online system is a sensitive and precise method for low-MW peptides (<3000 Da) even picomol quantities can be detected. However, as the MW of the analytes increases, the ionization of peptides becomes more difficult and decreases the sensibility of the FAB-MS (112). Electrospray ionization (ESI-MS) was found to be an efficient method for the determination of molecular masses up to 200,000 Da of labile biomolecules, with a precision of better than 0.1%. Molecular weights of peptide standards and an extensive hydrolysate of whey protein were determined by the HPLC-MS-FAB online system and supported by MALDI-TOF (112). Furthermore, HPLC-MS-FAB results were compared with those of Fast Performance Liquid Chro-motography (FPLC) analysis. Mass spectrometry coupled with multidimensional automated chromatography for peptide mapping has also been developed (9f,l 12a). 

J Slobodnik, AC Hogenboom, AJH Louter, UAT Brinkman. Integrated system for online gas and liquid chromatography with a single mass-spectrometric detector for the automated analysis of environmental samples. J Chromatogr A 730 353-371, 1996. 

On-Line Systems Flowing MMLLE systems have been established in different layouts with automation and on-line hyphenation to GC and HPLC analysis. An automated on-line FS-MMLLE-GC system with a loop-type interface compatible with LVI was used for the extraction of pesticides and PAHs in surface waters.86 In another study, pressurized hot water extraction (PH WE) was coupled on-line to a FS-MMLLE-GC-FID system and applied to the analysis of PAHs in soil, where MMLLE was used as a cleanup and concentration step of the PH WE extract prior to final GC analysis.87 In addition, an HF-MMLLE setup was incorporated in PHWE and GC, resulting in an online PHWE-HF-MMLLE-GC system, where the HF membrane module contained 10-100 HFs. The system served for the extraction and analysis of PAHs in soil and sediments ... 

Today, scientists have an extensive array of analytical methods at their disposal photometry, HPLC, GC analysis and MS online. Samples of submersion cultures are made available with the aid of a tapping and preparation unit. Complete R D programmes can be run automatically nowadays and automation will foreseeably take over production processes. Historically, automation has strong roots in Switzerland, as is shown by the contribution by W. Beyeler et al. [16] in this issue. With the current period of automation, a century comes to a close that - once it had overcome the myth of spontaneous creation - has tried to establish control over spontaneous natural processes by simple means. 

HPLC not only provides a very good cleanup of the sample performing separation of PCBs from other similar organic compounds such as polycyclic aromatic hydrocarbons (PAHs), but it also allows the separation of coplanar non-ortho substituted PCBs. Coupling of the extraction system with an online LC-GC system allows the whole analysis to be done in a closed system, minimizing the risk of sample contamination or loss of analytes. Moreover, automating the cleanup procedure may reduce the time of analysis and increase overall reproducibility. 

Liquid chromatographic systems for environmental pesticide analysis have been extensively reviewed in a previous paper. Nowadays, LC is the technique of choice for analyzing those pesticides which, being thermolabile, are not amenable to direct GC analysis, such as phenylurea and SUHs. LC methods of analysis also have the important advantage over GC methods in that online pre- and postcolumn reaction systems are compatible with LC instrumentation. Furthermore, the LC apparatus can easily be coupled online with the enrichment step using SPE on precolumns, thereby making the analysis fully automated. 

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