title: Least absolute shrinkage and selection operator and dimensionality reduction techniques in quantitative structure retention relationship modeling of retention in hydrophilic interaction liquid chromatography.
abstract: The objective of this study was to model the retention of nucleosides and pterins in hydrophilic interaction liquid chromatography (HILIC) via QSRR-based approach. Two home-made (Amino-P-C18, Amino-P-C10) and one commercial (IAM.PC.DD2) HILIC stationary phases were considered. Logarithm of retention factor at 5% of acetonitrile (logkACN) along with descriptors obtained for 16 nucleosides and 11 pterins were used to develop QSRR models. We used and compared the predictive performance of three regression techniques: partial least square (PLS), the least absolute shrinkage and selection operator (LASSO), and the LASSO followed by stepwise multiple linear regression. The highest predictive squared correlation coefficient (QLOOCV(2)) in PLS analysis was found for Amino-P-C10 (QLOOCV(2)=0.687) and IAM.PC.DD2 (QLOOCV(2)=0.506) and the lowest for IAM.PC.DD2 (QLOOCV(2)=-0.01). Much higher values were obtained for the LASSO model. The QLOOCV(2) equaled 0.9 for Amino-P-C10, 0.66 for IAM.PC.DD2 and 0.59 for Amino-P-C18. The combination of LASSO with stepwise regression provided models with comparable predictive performance as the LASSO, however with possibility of calculating the standard error of estimates. The use of LASSO itself and in combination with classical stepwise regression may offer greater stability of the developed models thanks to more smooth change of coefficients and reduced susceptibility towards chance correlation. Application of QSRR-based approach, along with the computational methods proposed in this work, may offer a useful approach in the modeling of retention of nucleoside and pterin compounds in HILIC.
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Daghir-Wojtkowiak
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin Street 7, 87-100, Toruń, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Bocian
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Kubik
authors.affiliation: Department of Toxicology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, M. Curie-Skłodowskiej 9, 85-094 Bydgoszcz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kośliński
authors.affiliation: Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin Street 7, 87-100, Toruń, Poland.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Buszewski
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: roman.kaliszan@gumed.edu.pl.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: markusz@gumed.edu.pl.
authors.forename: Michał Jan
authors.initials: MJ
authors.lastname: Markuszewski
mesh_terms: D002623:Chemistry Techniques, Analytical / Q000379:methods* / Q000592:standards*; D002853:Chromatography, Liquid; D057927:Hydrophobic and Hydrophilic Interactions; D016018:Least-Squares Analysis; D016014:Linear Models; D008962:Models, Theoretical
keywords: Hydrophilic interaction liquid chromatography (HILIC); Least absolute shrinkage and selection operator (LASSO); Nucleosides; Pterins; QSRR; Stationary phases