Least absolute shrinkage and selection operator and dimensionality reduction techniques in quantitative structure retention relationship modeling of retention in hydrophilic interaction liquid chromatography

• We proposed an approach to model the retention in HILIC mode using QSRR.
• Polar compounds in HILIC mode can be modeled via QSRR using quadratic equation.
• LASSO proved to be an efficient variable selection method in QSRR modeling.
• LASSO with stepwise selection offered good predictive performance of the models.

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 (log kACN) 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 (QLOOCV2) in PLS analysis was found for Amino-P-C10 (QLOOCV2=0.687) and IAM.PC.DD2 (QLOOCV2=0.506) and the lowest for IAM.PC.DD2 (QLOOCV2=−0.01). Much higher values were obtained for the LASSO model. The QLOOCV2 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.