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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

Citation

Taraji, M and Haddad, PR and Amos, RIJ and Talebi, M and Szucs, R and Dolan, JW and Pohl, CA, Rapid method development in hydrophilic interaction liquid chromatography for pharmaceutical analysis using a combination of quantitative structure-retention relationships and design of experiments, Analytical Chemistry, 89, (3) pp. 1870-1878. ISSN 0003-2700 (2017) [Refereed Article]

Copyright Statement

Copyright 2016 American Chemical Society

DOI: doi:10.1021/acs.analchem.6b04282

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:QSRR, method scoping, HILIC, QbD, DoE
Research Division:Chemical Sciences
Research Group:Analytical Chemistry
Research Field:Separation Science
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Chemical Sciences
Author:Taraji, M (Ms Maryam Taraji)
Author:Haddad, PR (Professor Paul Haddad)
Author:Amos, RIJ (Dr Ruth Amos)
Author:Talebi, M (Dr Mohammad Talebi)
ID Code:113934
Year Published:2017
Funding Support:Australian Research Council (LP120200700)
Web of Science® Times Cited:7
Deposited By:Chemistry
Deposited On:2017-01-30
Last Modified:2017-10-12
Downloads:0

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