Experimental Determination of CHI

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  

The values ( )o for the calibration standards are estimated by plotting log fe values as a function of organic modifier concentrations assessed from at least three iso-cratic experiments and obtained with [39]  

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. 

The CHI index is reportedly a relevant parameter in quantitative structure-activity relationship (QSAR) studies [41]. With this approach, log P could be determined in the range -0.45 logP 7.3 [40]. CHI was determined for more than 25000 compounds with excellent reproducibility (within 2 index units) and reported in a GlaxoSmithKline database [11]. Two main drawbacks were identified using this approach (i) the assumptions used in Ref [7], i.e. that S is constant for all compounds and that the system dwell volume is excluded in calculations, yield some discrepancies in the resulting log P, and (ii) the set of gradient calibration 

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