Chi-values

The CHI can be obtained without preliminary method development direcdy from a single fast-gradient run with a cycle time less than 15 min with a 150-mm column [40] or 5 min with 50-mm column [42]. In this case, the obtained retention time, tr, is expressed within an organic phase concentration (< o) scale using a calibration set of compounds. CHI value can be obtained from ... 

In case of fast gradient (below 15 min), S could be considered constant for all the investigated molecules and wiU only have a small influence on the retention time of the compounds. Thus, the gradient retention times, of a calibration set of compounds are linearly related to the ( )o values [39]. Moreover, Valko et al. also demonstrated that the faster the gradient was, the better the correlation between t, and < )o [40]. Once the regression model was established for the calibration standards, Eq. 8 allowed the conversion of gradient retention times to CHI values for any compound in the same gradient system. Results are then suitable for interlaboratory comparison and database construction. The CH I scale (between 0 and 100) can be used as an independent measure of lipophilicity or also easily converted to a log P scale. 

Valko et al. [37] developed a fast-gradient RP-HPLC method for the determination of a chromatographic hydrophobicity index (CHI). An octadecylsilane (ODS) column and 50 mM aqueous ammonium acetate (pH 7.4) mobile phase with acetonitrile as an organic modifier (0-100%) were used. The system calibration and quality control were performed periodically by measuring retention for 10 standards unionized at pH 7.4. The CHI could then be used as an independent measure of hydrophobicity. In addition, its correlation with linear free-energy parameters explained some molecular descriptors, including H-bond basicity/ acidity and dipolarity/polarizability. It is noted [27] that there are significant differences between CHI values and octanol-water log D values. 

The retention depends on the nature of both the stationary phase and the organic modifier in the mobile phase. Therefore CHI values obtained using different systems show different sensitivities towards solute characteristics. This has been studied systematically and used for the quantitative calculation of solute molecular descriptors (H-bond donor capacity, H-bond acceptor capacity and dipolarity/polarizability) for application in a general solvation equation [21]. 

The behavior of the detection algorithm is illustrated by adding a bias to some of the measurements. Curves A, B, C, and D of Fig. 3 illustrate the absolute values of the innovation sequences, showing the simulated error at different times and for different measurements. These errors can be easily recognized in curve E when the chi-square test is applied to the whole innovation vector (n = 4 and a = 0.01). Finally, curves F,G,H, and I display the ratio between the critical value of the test statistic, r, and the chi-value that arises from the source when the variance of the ith innovation (suspected to be at fault) has been substantially increased. This ratio, which is approximately equal to 1 under no-fault conditions, rises sharply when the discarded innovation is the one at fault. 

Additional examination of the model s fit is performed through the comparison of the experimental and predicted bioactivities and is needed to statistically ensure that the models are sound. The methods of chi (%) and root-mean squared error (RMSE) are performed to determine if the model possesses the predictive quality reflected in the R2. The use of RMSE shows the error between the mean of the experimental values and predicted activities. The chi value exhibits the difference between the experimental and predicted bioactivities ... 

Tolman chi value, isomeric ratio of LRh(CO)2H, normal over/so ratio, normal-a 6ehy6e product, isomerized product 2-octene, and turnover frequency. 

While low serum cholesterol levels have been observed in malnourished patients, largely as a result of decreased synthesis of lipoproteins in the liver, hypocholesterolemia occurs later in the course of malnutrition and is therefore not useful as a screening test. PEM usually results in low serum urea nitrogen (BUN), urinary urea, and total nitrogen. Estimation of 24-h urine creatinine excretion is also a valuable biochemical index of muscle mass (when there is no impairment in renal function). The urinary CHI is correlated to lean body mass and anthropometric measurements. In edematous patients, for whom the extracellular fluids contribute to body weight and spuriously high body mass index values, the decreased CHI values are especially useful in diagnosing malnutrition. 

Fig. 12.6. The plot of CHI values obtained at various starting-mobile-phasc pHs for a basie compound.

Keeping the conditions the same as those used for the test mixture the CHI value of compound X can be calculated as CHlx = + B. In our experience a... 

Fig. I2.lt). The plot of the chromatographic hydrophobicity index (CHI) values obtained on Inertsil ODS and lAM column (from Ref. 64 ).

Fig. 12.19) that seemed to have the widest range of coefficients for the molecular descriptors in the solvation equation. Table 12.10 shows the solvation equations obtained and their normalised coefficients. The equations were obtained from the chromatographic hydrophobicity index data (CHI) of the compounds listed in Table 12.7 by using a 2.5 min linear gradient of the oi anic solvent from 0 to 1009F with 2 ml/min flow rate. The columns used were 4.6 x 50 mm short columns. The application of this fast gradient method makes it possible to obtain CHI values in a given HPLC system in 5 min. 

Using the measured CHI data of the model compounds we can set up a correlation equation to express the H-bond acidity (a), H-bond basicity (f) and the polarisability-dipolarity (n) parameters by the CHI values obtained on a particular stationary phase with a particular mobile phase. The plot of the database descriptors as a function of the estimated ones based on the measured CHI values can be seen in Figs. 12.20-12.22. The best equations for the estimation of the descriptors are also shown in the figures. It can be seen that the CHI values obtained on Luna C-18 columns with acetonitrile and trifluoroethanol gradients are used for the fi and the ir calculations. The CHI values... 

With the application of the fast gradient CHI values it takes approximately six times five minutes to determine the basic molecular properties of newly synthesised drug molecules. The method can be fully automated, and small impurities can be separated during the HPLC run so that they do not disturb the measurements. Very small quantities of compounds are used for these measurements, and we believe that this method will help design soluble drug molecules with the desired absorption, and brain penetration, etc., by using the general solvation equations already known for these systems. 

Based on the (po concept, a fast gradient method RP-HPLC has been proposed to determine the chromatographic hydrophobicity index (CHI) as a high-throughput alternative to other lipophilicity measures.For this purpose, gradient retention times (tg) are measured and converted to CHI values by means of a calibration equation, derived by a set of standards with well-determined CHI (tpo) values ... 

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