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Rapid method development in hydrophilic interaction liquid chromatography for pharmaceutical analysis using a combination of quantitative structure-retention relationships and design of experiments

journal contribution
posted on 2023-05-19, 01:12 authored by Maryam Taraji, Paul HaddadPaul Haddad, Amos, RIJ, Mohammad TalebiMohammad Talebi, Szucs, R, Dolan, JW, Pohl, CA
A design-of-experiment (DoE) model was developed, able to describe the retention times of a mixture of pharmaceutical compounds in hydrophilic interaction liquid chromatography (HILIC) under all possible combinations of acetonitrile content, salt concentration, and mobile-phase pH with R2 > 0.95. Further, a quantitative structure–retention relationship (QSRR) model was developed to predict retention times for new analytes, based only on their chemical structures, with a root-mean-square error of prediction (RMSEP) as low as 0.81%. A compound classification based on the concept of similarity was applied prior to QSRR modeling. Finally, we utilized a combined QSRR-DoE approach to propose an optimal design space in a quality-by-design (QbD) workflow to facilitate the HILIC method development. The mathematical QSRR-DoE model was shown to be highly predictive when applied to an independent test set of unseen compounds in unseen conditions with a RMSEP value of 5.83%. The QSRR-DoE computed retention time of pharmaceutical test analytes and subsequently calculated separation selectivity was used to optimize the chromatographic conditions for efficient separation of targets. A Monte Carlo simulation was performed to evaluate the risk of uncertainty in the model’s prediction, and to define the design space where the desired quality criterion was met. Experimental realization of peak selectivity between targets under the selected optimal working conditions confirmed the theoretical predictions. These results demonstrate how discovery of optimal conditions for the separation of new analytes can be accelerated by the use of appropriate theoretical tools.

Funding

Australian Research Council

Pfizer

Thermo Fisher Scientific Australia

History

Publication title

Analytical Chemistry

Volume

89

Pagination

1870-1878

ISSN

0003-2700

Department/School

School of Natural Sciences

Publisher

Amer Chemical Soc

Place of publication

1155 16Th St, Nw, Washington, USA, Dc, 20036

Rights statement

Copyright 2016 American Chemical Society

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the chemical sciences

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