Reaction monitoring, continuous

To illustrate the concept of combining analytics to improve process understanding an example chemical reaction was run using a Cellular Process Chemistry Systems (CPC) continuous feed micro reactor. This microreactor is configured to operate as a small-scale chemical production plant. It has two reactant input lines and two solvent/wash lines. The thermally controlled microreactor block of the continuous feed reactor has a total internal volume of 50 pL. The reactor system contains active control for both temperature and feed rate of the two reactants. The system flows product from the microreactor block to a residence time module (12 mL volume) and then out of the reactor for product collection and work-up. 

The primary objective of this study was to develop a general chemistry test bed for evaluating and optimizing various chemistries and on-line analytical sensors. 

This was initiated by first choosing a simple test bed chemical reaction to evaluate and understand the functionality, flexibility and limitations of the microreactor platform. The reaction of acetic acid and methanol to form methyl ester was selected because the reaction was temperature sensitive and of minimal toxicity. This chemistry has been extensively studied in the author s laboratory previously by Raman spectroscopy in a typical batch reactor. The batch reactor results were a very useful foundation when trying to understand the reaction processes in the microreactor. The microreactor experiments were structured to study reaction response to reactor parameter changes (temperature and flow rate) using Raman spectroscopy. 

The formation of methyl acetate was monitored using a modified flow cell equipped with a Raman baUprobe and a back pressure regulating valve to reduce perturbations in the flow. The Raman system was set to acquire the average of two 

5-second integrations for each spectrum (15 s total acquisition time). The reaction was run at 50 C for a total of 70 min. The flow rate through the reactor varied from less than 1 mb min to greater than 10 mb min . The reactor temperature was crudely controlled using the reactor operating software. 

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Continual cardiac monitoring assists the nurse in assessing the patient for adverse drug reactions. If the patient is acutely ill or is receiving one of these drugs par-enterally, the nurse measures and records the fluid intake and output. The primary health care provider may order subsequent laboratory tests to monitor the patient s progress for comparison with tests performed in the preadministration assessment, such as an ECG, renal and hepatic function tests, complete blood count, serum enzymes, and serum electrolytes. The nurse reports to the primary care provider any abnormalities or significant... 

This practical set-up may also be used for reaction monitoring by placing the capillary into a reaction mixture and continually acquiring mass spectra, which thus allows the analyst to examine changes in its composition. 

Figure 5.58 Reconstructed LC-MS-MS ion chromatograms for selected-reaction monitoring of methoxyfenozide using the m/z 367 to m/z 149 transition from the continual post-column infusion of a standard solution of analyte during the HPLC analysis of a...

NMR Acquisition in Reaction Monitoring Stopped- and Continuous-flow... 

Although limited by sensitivity, chemical reaction monitoring via less sensitive nuclei (such as 13C) has also been reported. In 1987 Albert et al. monitored the electrochemical reaction of 2,4,6-tri-t-butylphenol by continuous flow 13C NMR [4]. More recently, Hunger and Horvath studied the conversion of vapor propan-2-ol (13C labeled) on zeolites using 1H and 13C in situ magic angle spinning (MAS) NMR spectroscopy under continuous-flow conditions [15]. 

Major categories of process Raman applications include reaction monitoring, in-process quality checks, and mobile or field point measurements. Quality control laboratory applications often are converted to a continuous process monitoring approach, or could simply be viewed as part of a larger production process. 

Table 2.1.3 (continued) Multiple reaction monitoring of amino acids for their tandem mass spectrometry quantitation. In daily practise not all mentioned amino acids are measured in one run, but a set often dedicated evaluation programs has been developed, covering groups of amino acids associated with groups of disorders. Amino acids presented in italics indicate stable-isotope-labeled internal standards ... 

To asolution of 15.0 g2,5-dimethoxy-(2-fluoroethylthio)benzaldehyde in 75 mL nitromethane there was added 1.35 g of anhydrous ammonium acetate, and the mixture was heated on the steam bath for 70 min (the progress of the reaction must be followed by continuous TLC monitoring). The clear deeply-colored solution was decanted from some insoluble material and the excess nitromethane removed under vacuum. There resulted 17.78 g of almost dry brick-red crystals which were dissolved in 110 mL boiling EtOAc. After cooling overnight in the... 

A flame-dried flask containing nitroethane (0.4 mL) and catalyst (10.4 mg, 20 pmol, 0.1 equiv) was cooled to —20 °C, and then treated with the imine (50.0 mg, 200 pmol, 1.0 equiv). Stirring was continued at —20 °C and the reaction monitored by gas chromatography (GC). On complete consumption of the imine, the solution was concentrated in vacuo and purified by FC on silica gel... 

Postoperatively, the anesthesiologist withdraws the anesthetic mixture and monitors the immediate return of the patient to consciousness. For most anesthetic agents, recovery is the reverse of induction that is, redistribution from the site of action rather than metabolism underlies recovery. The anesthesiologist continues to monitor the patient to be sure that there are no delayed toxic reactions, for example, diffusion hypoxia for nitrous oxide, and hepato-toxicity with halogenated hydrocarbons. 

Two approaches are often used to improve the detection limit, including selected ion monitoring (SIM) and multiple reaction monitoring (MRM). In LC/MS studies, it is often desirable to increase detection sensitivity by hmit-ing the mass analyzer scan to just one ion— that is, SIM. In this mode, a single ion of interest is monitored continuously by a mass spectrometer and no other ions are detected. This results in signihcant improvement of signal-to-noise ratio. SIM trades specihcity for sensitivity. In general, the sensitivity in SIM is increased by a factor of 100 to 1000 over full-scan mass spectra. This can be quite useful in detection and quantihcation of specihc compounds at low levels. 

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