%0 Journal Article
%T Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods
%A Avdeef
%A Alex
%J -
%D 2019
%R 10.5599/admet.698
%X Sa£¿etak This commentary compares 233 CheqSol intrinsic solubility values (log S0) reported in the Wiki-pS0 database for 145 different druglike molecules to the 838 log S0 values determined mostly by the saturation shake-flask (SSF) method for 124 of the molecules from the CheqSol set. The range of log S0 spans from -1.0 to -10.6 (log molar units), averaging at -3.8. The correlation plot between the two methods indicates r2 = 0.96, RMSE = 0.34 log unit, and a slight bias of -0.07 log unit. The average interlaboratory standard deviation (SDi) is slightly better for the CheqSol set than that of the SSF set: SDiCS = 0.15 and SDiSSF = 0.24. The intralaboratory errors reported in the CheqSol method (0.05 log) need to be multiplied by a factor of 3 to match the expected interlaboratory errors for the method. The scale factor, in part, relates to the hidden systematic errors in the single-lab values. It is expected that improved standardizations in the ¡®gold standard¡¯ SSF method, as suggested in the recent ¡®white paper¡¯ on solubility measurement methodology, should make the SDi of both methods be about ~0.15 log unit. The multi-lab averaged log S0 (and the corresponding SDi) values could be helpful additions to existing training-set molecules used to predict the intrinsic solubility of drugs and druglike molecules
%K Interlaboratory solubility measurement errors
%K aqueous intrinsic solubility
%K shake-flask solubility
%K potentio- metric solubility
%K thermodynamic solubility
%K Henderson-Hasselbalch equation
%U https://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=326673