Flow probe

Irganox 1076 [octadecyl-3-(3,5-di-t-butyl-4-hydroxyphenyl) propionate], 2,6-di-t-butyl-4-methylphenol and diisooctyl phthalate were analyzed by GPC interfaced with both electrospray mass spectrometry (ESI-MS) and NMR.1 A deuterochloroform solvent was used. It was noted that a parallel arrangement was necessary to avoid backpressure on the NMR flow-probe that can... 

Special mention may still be made of the Ingold199 range of industrial immersion and continuous-flow probes for pH measurements at high pressures, as... 

The instrumental setup for capillary HPLC-NMR coupling is shown in Figure 4.6. The capillary pump is connected via 50 pm capillaries between the capillary HPLC pump, the UV detector, and the NMR flow probe. 

Smaller diameter probes reduce sample volumes from 500 to 600 pi typical with a 5 mm probe down to 120-160 pi with a 3 mm tube. By reducing the sample volume, the relative concentration of the sample can be correspondingly increased for non-solubility limited samples. This dramatically reduces data acquisition times when more abundant samples are available or sample quantity requirements when dealing with scarce samples. At present, the smallest commercially available NMR tubes have a diameter of 1.0 mm and allow the acquisition of heteronuclear shift correlation experiments on samples as small as 1 pg of material, for example in the case of the small drug molecule, ibu-profen [5]. In addition to conventional tube-based NMR probes, there are also a number of other types of small volume NMR probes and flow probes commercially available [6]. Here again, the primary application of these probes is the reduction of sample requirements to facilitate the structural characterization of mass limited samples. Overall, many probe options are available to optimize the NMR hardware configuration for the type and amount of sample, its solubility, the nucleus to be detected as well as the type and number of experiments to be run. 

The basic components of an LC-NMR system are some form of chromatographic instrument and an NMR spectrometer equipped with a flow-probe, as shown in Fig. 19.17. In terms of the chromatography of choice, there are many examples in the literature of a wide array of separation instruments employed, from SFC to capillary electrophoresis (CE) [87,88]. By far the most common method (not necessarily the best choice from a separation point of view) of achieving the desired separation is through HPLC. There are many commercial... 

It is appropriate at this time to discuss some of the limitations associated with LC-NMR. It is more accurate to say the limitations of the NMR spectrometer in an LC-NMR instrument. As compared to MS, NMR is an extremely insensitive technique in terms of mass sensitivity. This is the key feature that limits NMR in its ability to analyze very small quantities of material. The key limiting factor in obtaining NMR data is the amount of material that one is able to elute into an active volume of an NMR flow-probe. The quantity of material transferred from the LC to the NMR flow-cell is dependant on several features. The first being the amount of material one is able to load on an LC column and retain the resolution needed to achieve the desired separation. The second is the volume of the peak of interest. The peak volume of your analyte must be reasonably matched to the volume of the flow-cell. An example would be a separation flowing at lml/min with the peak of interest that elutes for 30 s. This corresponds to a peak volume of 500 pi, which clearly exceeds the volume of the typical flow-cell. This is the crux of the problem in LC-NMR. There is a balance that must be struck between the amount of compound needed to detect a signal in an... 

While the early days of LC-NMR and LC-NMR-MS were plagued by the poor sensitivity of the NMR spectrometer, the recent probe design advances have provided a means to potentially overcome this hurdle. As reported in the literature, it is possible to get both ID and 2D homo-nuclear and heteronuclear correlation data on sub micrograms of materials in quite complex mixtures utilizing cryogenic flow-probes in tandem with SPE peak trappings [98]. While these technologies are still in their infancy, they have the potential to revolutionize LC-NMR as a structure elucidation technique. 

To study the effect of PGDN on cerebral blood flow, Godin et al. (1995) injected male Sprague-Dawley rats (through a jugular vein cannula) with PGDN at 0.1 to 30 mg/ kg and measured cerebral blood flow with a fiberoptic laser-Doppler flow probe in contact with the brain. Following a small initial drop in cerebral perfusion that lasted 1 min, blood flow rapidly increased and reached a maximum 2 min after injection. The increase in perfusion was correlated with dose, but due to the small number of animals and individual variability, a clear dose-response relationship was not obtained. 

Direct determination of portal blood flow rate is difficult and would generally require placement of an electronic flow probe in each animal. However the technique proposed by Hoffman et al. utilised tritiated water as an absorption probe (i.e. internal standard) [89], By dosing and sampling drug/ absorption probe concurrently, factors such as variable portal blood flow rate are normalised between experiments. 

Regional blood flow Flow probes, Doppler, microspheres Wakefield et al.103... 

Recent LC-NMR Probe Developments 7.4.2.1 Cryogenically Cooled Flow Probes... 

This new hyphenated analytical system integrates capillary LC with NMR detection. The capillary LC-NMR system is comprised of an NMR spectrometer equipped with a capillary flow probe and the capillary LC. The capillary flow probe has a flow-cell design with an active sample volume of only 1 or 1.5 pL. This volume is chosen to match the typical peak volumes of capillary LC separation. 

While NMR spectra possess a high information content, this confers a level of complexity that can be obstructive if a quick and simple answer is required. The use of NMR flow probes has reduced the time taken to acquire a spectrum to 2-3 min and flow NMR has consequently found considerable application in robot synthesis, multiple parallel synthesis (MPS) or combinatorial chemistry. Since H possesses 5600 times the receptivity of it is inevitable that it will continue to be the nucleus of choice in this area, complicating the analysis. Unless automatic analysis is able to transcend the aid to interpretation role and into the confirm or refute the structure role, the higher information content of the NMR spectrum constitutes a threat rather than an opportunity. 

The magnets utilized in these systems are typically neodymium-iron or samarium-cobalt disks with appropriately designed pole shoes that are placed with a variable air gap between them to accommodate an NMR probe designed to allow sample tubes (or flow probes) of 5 0 mm diameter. The magnet disks are typically wrapped along their sides with double wound wire to heat magnets to maintain a stable 35 °C operating... 

Transfer directly into flow probe with deuterated solvent... 

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