Integral plot

The primary objective of integration plot analysis is to analyze the data on influx of the test substrate from the circulating blood to the retina (i.e., blood-to-retina direction) across the BRB after intravenous administration of the test substrate. The advantage of this approach is that it allows reliable determination of the retinal uptake (i.e., clearance) of the test substrate which has a slow permeability across the BRB [28], On the other hand, due to the intravenous injection, interference by endogenous substrates and plasma-protein binding of the test substrate can produce an unseemingly low estimate of the retinal uptake. 

The apparent retinal influx clearance,. Kin,retina expressed as mL/(min g retina), of the test substrate labeled with either [3 H] or [14C] from the circulating blood to the retina is determined by integration plot analysis. In brief, rats are anesthetized, followed by injection of the test substrate (e.g., an [3H]-labeled compound, about 10 /u.Ci/head) into the femoral vein. After collection of plasma samples, rats are decapitated and the retinas removed. The retinas are dissolved in 2 N NaOH and subsequently neutralized with 2 N HC1. The radioactivity of retinal cell lysates is measured by liquid scintillation spectrometry. As an index of the retinal distribution characteristics of the radiolabeled test substrate, the apparent retina-to-plasma concentration ratio (Vd) as a function of time is used. This ratio [Vd(Q] (mL/g retina) is defined as the amount of [3H] per gram retina divided by that per milliliter plasma, calculated over the time-period of the experiment. The Kjn,retina can be described by the following relationship ... 

Figure 14.3 Integration plot of the initial uptake of [3H]adenosine by the retina after intravenous administration (A) and retinal uptake index (RUI) of [3H]adenosine and [3H]D-mannitol (B). A [3H]Adenosine (10 //.Ci/head) was injected into the femoral vein. B A test compound, [3H]adenosine or [3H]D-mannitol (10 //Ci/head), and a reference compound, [14C]n-butanol (0.1 //Ci/head), were injected into the common carotid artery in the presence or absence of 2 mM inhibitors. p < 0.05, significantly different from the control. Data from Biochimica et Biophysica Acta, 1758, Nagase et al., Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. 13-19, 2006, with permission from Elsevier.

Because tissue-specific vectors are aimed at increasing the influx of a drug into the target, assessment of unidirectional transport from the circulating plasma into the target organ is essential. In this context, integration plot analysis is a convenient in vivo method in which a tracer amount of vector is injected intravenously and the plasma (Cp) and tissue (Ct) con-... 

Figure 5.4. Schematic diagram for (a) the integration plot analysis and (h) renal processing of alkylglycoside.

Quantitative measurements in NMR are based on the area of the signals present in the spectrum. Signal areas can be produced as numerical values proportional to the area or, on less modern instruments, from the integration plots that are superimposed on the spectrum (Fig. 9.1). For the proton, the precision obtained in area measurements does not exceed l % even if continuous wave instruments are used at slow scanning speeds. In l3C NMR, it is preferable to add a relaxation reagent in order to avoid saturation related to relaxation times that alter the intensity of the signal. Using the molar ratios that are easily accessible from the spectrum, it is possible to deduce concentrations. 

Figure 2 Comparison between the uptake clearance obtained in vivo and that extrapolated from the in vitro transport study of endothelin antagonists. In vivo uptake clearance of endothelin antagonists (BQ-123, BQ-518, BQ-485, compound A) was evaluated by integration plot analysis using the plasma concentration-time profile after intravenous administration (500 nmol/kg) and the amount of drug in the liver and that excreted in the bile. In vitro hepatic uptake clearance was measured using isolated rat hepatocytes and was extrapolated to the in vivo uptake clearance assuming the well-stirred model. Source From Ref. 5.

Using split injection mode, inject 1 to 5 xL of the standards into the chromatograph. Determine the peak areas by electronic integration. Plot peak area against concentration for each analyte corrected for the blank to construct a standard curve. Determine the concentration of additives and byproducts by comparison to the standard curve. The sum of the concentrations of the impurities and stabilizers is less than 1.0%. The order of elution and approximate retention times, in minutes, are as follows methyl chloride 2.8 vinyl chloride 3.0 ethyl chloride 3.5 propylene oxide 4.1 2-methyl-2-butene 4.5 vinylidene chloride 4.6 dichloromethane 5.3 trans-1,2-dichloroclhylene 5.9 chloroform 8.7 cyclohexane 10.5 and carbon tetrachloride 12.0. 

The area under the curve between x o and Xj is the value of the integral. Plot the equilibrium curve for the more volatile component on x - y diagram as shown in Figure 8-33. Then, select values of xq from the operating line having the constant slope, L/V, from equation... 

Integrators are manufactured by many companies (for example Hewlett-Packard, Spectro Physics, Varian). Many integrators plot the chromatography mn, record the retention times of peaks, calculate the areas under the peaks automatically and print this data at the end of the mn. 

Determine the activity coefficients of the solute at the molalities 0.1, 0.5 and 1.0 by graphical evaluation of the integrals. (Plot j/m against m for the first, and 0/m against 6 for the second when is the latter negligible )... 

Finally, we explain how we have obtained the data in Figs. 23.4 and 23.5. The data are simply random numbers in the range of 0-1. At a time of 0.5 units, to each random number a constant value of 0.05 has been added. Therefore, a significant portion of only 5% of the total scattering has been introduced. In Fig. 23.4, a change is literally invisible, but in the integral plot of Fig. 23.5 the curve is moving up. 

To demonstrate the increased level of detail that is available because parent molecules can be detected without fragmentation for individual (k, 1) combinations, we have plotted the relative abimdances in a different way. Figure 11.11 shows relative peak integrals plotted in a grid of k and 1. 

J-integral plot for UHMWPE compact tensile specimen. 

Figure 2. Integral Plot of Conversion vs. Polymer Composition (50/50 Mole Ratio)...

Pump. A constant flow rate of the mobile phase is another essential condition for quantitative analysis. Especially for peak area quantification. even small variations in flow can have a disastrous effect because the recorder or integrator plots the concentration (signal intensity) versus analysis time (not versus flow rate). Therefore a variation in flow automatically influences the recorded peak area. Quantification over peak height is not so strongly influenced by fluctuations in the flow of the mobile phase. 

The above sections have presented the most common data visualisation methods for a given data set. More complex forms can be created by combining different simple data visualisation methods into a final integrated plot. Alternatively, the data could be transformed (changed in some manner) before being plotted. The different techniques that are available to accomplish this depend strongly on the intended application and will be introduced in the relevant sections in later chapters. Often such plots are created when there is multiple information that needs to be displayed,... 

Figure 6.19 Experimental tests of the Forster theory of long-range transfer of electronic energy, (a) Dependence of transfer rate constant on spectral overlap integral. Plot of logger against log 7. From Ref. [40]. (b) Distance-dependence of the energy transfer efficiencies in dansyl-(L-prolyl)n-a-naphthyl, n = I to 12. Plotof ln( - 1) against In R. From Ref. [42].

The values utilized for preparing the graphical integration plot are given in the first five columns of Table 3-5. As a basis for calculations, propanol was taken as component 1 and benzene as component 2. As the check point, the value for the partial pressure of propanol of 28.6 mm. Hg at a mol fraction of propanol of 0.180 was chosen. 

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