In Silico Method Development of Achiral and Chiral Tandem Column Reversed-phase Liquid Chromatography for Multicomponent Pharmaceutical Mixtures

Tandem column liquid chromatography (LC) is a convenient, cost-effective approach to resolve multicomponent mixtures by serially coupling columns on readily available one-dimensional separation systems without specialized user training. Yet, adoption of this technique remains limited, mainly due to...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2022-03, Vol.94 (9), p.4065-4071
Main Authors: Haidar Ahmad, Imad A, Kiffer, Alaina, Barrientos, Rodell C, Losacco, Gioacchino Luca, Singh, Andrew, Shchurik, Vladimir, Wang, Heather, Mangion, Ian, Regalado, Erik L
Format: Article
Language:English
Subjects:
Chemistry
Chromatography
Chromatography, Liquid - methods
Chromatography, Reverse-Phase
Column chromatography
Elution
Experimentation
Industrial applications
Liquid chromatography
Metabolites
Mixtures
Optimization
Peptides
Pharmaceutical Preparations
Pharmaceuticals
Retention
Selectivity
Separation
User training
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Summary:Tandem column liquid chromatography (LC) is a convenient, cost-effective approach to resolve multicomponent mixtures by serially coupling columns on readily available one-dimensional separation systems without specialized user training. Yet, adoption of this technique remains limited, mainly due to the difficulty in identifying optimal selectivity out of many possible tandem column combinations. At this point, method development and optimization require laborious “hit-or-miss” experimentation and “blind” screening when investigating different column selectivity without standard analytes. As a result, many chromatography practitioners end up combining two columns of similar selectivity, limiting the scope and potential of tandem column LC as a mainstay for industrial applications. To circumvent this challenge, we herein introduce a straightforward in silico multifactorial approach as a framework to expediently map the separation landscape across multiple tandem columns (achiral and chiral) and eluent combinations (isocratic and gradient elution) under reversed-phase LC conditions. Retention models were built using commercially available LC simulator software showcasing less than 2% difference between experimental and simulated retention times for analytes of interest in multicomponent pharmaceutical mixtures (e.g., metabolites and cyclic peptides).
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.1c05551