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https://doi.org/10.5599/admet.698

Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods

Alex Avdeef   ORCID icon orcid.org/0000-0002-3139-5442 ; in-ADME Research, 1732 First Avenue, #102, New York, NY 10128, USA

Fulltext: english, pdf (681 KB) pages 210-219 downloads: 399* cite
APA 6th Edition
Avdeef, A. (2019). Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods. ADMET and DMPK, 7 (3), 210-219. https://doi.org/10.5599/admet.698
MLA 8th Edition
Avdeef, Alex. "Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods." ADMET and DMPK, vol. 7, no. 3, 2019, pp. 210-219. https://doi.org/10.5599/admet.698. Accessed 5 Dec. 2020.
Chicago 17th Edition
Avdeef, Alex. "Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods." ADMET and DMPK 7, no. 3 (2019): 210-219. https://doi.org/10.5599/admet.698
Harvard
Avdeef, A. (2019). 'Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods', ADMET and DMPK, 7(3), pp. 210-219. https://doi.org/10.5599/admet.698
Vancouver
Avdeef A. Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods. ADMET and DMPK [Internet]. 2019 [cited 2020 December 05];7(3):210-219. https://doi.org/10.5599/admet.698
IEEE
A. Avdeef, "Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods", ADMET and DMPK, vol.7, no. 3, pp. 210-219, 2019. [Online]. https://doi.org/10.5599/admet.698

Abstracts
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.

Keywords
Interlaboratory solubility measurement errors; aqueous intrinsic solubility; shake-flask solubility; potentio- metric solubility; thermodynamic solubility; Henderson-Hasselbalch equation

Hrčak ID: 224004

URI
https://hrcak.srce.hr/224004

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