Direct-infusion

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

Direct Infusion ESMS of Cell Extracts in the Flow Injection Mode (FIESMS)... 

DIRECT INFUSION ESMS OF CRUDE CELL EXTRACTS... 

DIRECT INFUSION ESMS OF CRUDE CELL EXTRACTS FOR HIGH-THROUGHPUT CHARACTERIZATIONS—METABOLIC FINGERPRINTING AND FOOTPRINTING... 

Castrillo, J. L. Hayes, A. Mohammed, S. Gaskell, S. J. Oliver, S. G. An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 2003, 62, 929-937. 

Microinjection of 8-OH-DPAT or flesinoxan into the LDT or the mPRF, where structures that act to promote and to induce REMS are located, selectively inhibited REMS in the cat and the rat (Sanford et al, 1994 Horner et al, 1997 Monti Jantos, 2003). Furthermore, direct infusion of WAY 100635 into the LDT increased REMS (Monti Jantos, 2004). 

In specific cases, when long chain compounds such as esters and TAGs have survived and have not yet been hydrolysed or oxidised, it may be useful to carry out soft ionisation techniques in order to fully characterise the structure of these biomarkers by direct infusion into an electrospray source after adapted purification treatments. 

To summarise, a fractionation step allows the isolation of the compounds of interest from the other molecular constituents, particularly from the fatty acids that are well-ionised. To compensate for the low ionisation yield of some compounds, such as TAGs, the solutions may be doped with a cation. Samples are then directly infused into the ion electrospray source of the mass spectrometer. A first spectrum provides an overview of the main molecular compounds present in the solution based on the peaks related to molecular cations. The MS/MS experiment is then performed to elucidate the structure of each high molecular compound. Table 4.2 shows the different methods of sample preparation and analysis of nonvolatile compounds as esters and TAGs from reference beeswax, animal fats and archaeological samples. 

McDougall G, Martinussen I and Stewart D. 2008. Towards fruitful metabolomics high throughput analyses of polyphenol composition in berries using direct infusion mass spectrometry. J Chromatogr B 871(2) 362-369. 

IGFs are often localized within various areas of the kidney. Direct infusion of IGF-I influences (usually enhances) renal function by a number of means, including promoting increased ... 

The fact that 5-HT and hallucinogens can facilitate motor transmission in the spinal cord (see above) suggested that these compounds might increase startle by actions on spinal excitatory 5-HT receptors. Consistent with this expectation, we have found that direct infusion of 5-HT or 5-MeODMT into the subarachnoid... 

The development of an easy-to-handle method for the qualitative and quantitative determination of surfactants in consumer products was the goal for applying ESI in the FIA-MS(+/—) mode by direct infusion into the mass spectrometer. In this way Ci2, Ci4, Ci6 and Ci8 ASs could be determined besides other anionics (LASs, alkylcarboxylates), nonionics (alkyl polyglucosides (APGs)) and cationics (quats and ester-quats). The methods applied for concentration and determination (MS-MS) helped to identify the compounds and in addition deuterated internal standards were applied for confirmation [57]. 

Figure 10.3 Whole-mass analysis of a monoclonal antibody. (A) Direct infusion of the antibody generates an envelope of high m/z ions ranging from 2000 to 3500. Deconvolution of the ion current signal gives the mass of the complete native molecule (147, 100.97 Da) and resolves some heterogeneity linked to the A-glycan structures. The major forms are consistent with molecules carrying biantennary structures capped with 0, 1, or 2 hexose (G = galactose) residues. (Data generated on an ESI-Q-Star instrument, Sciex-Applied Biosystems.)...

The two most common LG/MS interfaces used for routine quantitative analyses are APCI and APT electrospray. The principles of these techniques in direct infusion analyses have been described earlier (see Sections 3.3 and 3.4). As APTelectrospray has a broader application profile, its use is more widespread than APCI. Other configurations including El, atmospheric pressure photoionization (APPl), and thermospray interfaces with liquid chromatographs are available but are less commonly used for high throughput or routine analysis. 

Lewis DA, Guzzetta AW, Hancock WS, Costello M. 1994. Characterization of humanized anti-TAC, an antibody directed against the interleukin 2 receptor, using electrospray ionization mass spectrometry by direct infusion, LC/MS, and MS/MS. Anal Chem 66 585. 

Many interfaces have been developed to meet these demanding challenges. Some of these coupling methods, such as the moving belt or the particle beam interface, are based on the concomitant elimination of the solvent before it enters the mass spectrometer. Other methods such as direct liquid introduction (DLI) or continuous flow FAB rely on splitting the flow of the liquid that is introduced into the interface in order to obtain a flow that can be directly infused into the ionization source. However, these types of interfaces can only handle a fraction of the liquid flow from the LC. 

Direct infusion mass spectrometry is a popular technique used by medicinal chemists to check the molecular mass of target compounds. In... 

TABLE 6 Direct Infusion FTMS Results on a Stressed Solid Dosage Formulation... 

While the idea of limited sample preparation and direct infusion into the MS are promising, this technique has not yet caught on in many laboratories. Ion suppression continues to be a limitation of this technique. It is also a limitation in other fast sample preparation methods and fast analyses. Protein precipitation is a quick and dirty technique, and many components from the plasma matrix remain. With this direct infusion into the MS, these matrix components are also sprayed into the source with the analytes of interest and can cause ion suppression. Additionally, many samples can contain several analytes, often including internal standards. In many instances, these analytes cause self-suppression when infused together into the source. With a proper sample cleanup such as SPE, either off-line or on-line, this technique may prove to be more useful in the future. 

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