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Orthogonal Separations in Reversed-Phase Chromatography

Agrawal, Roopali, Belemkar, Sateesh, Bonde, Chandrakant
Chromatographia 2018 v.81 no.4 pp. 565-573
drugs, energy, geometry, hydrogen, models, reversed-phase liquid chromatography
A method development for molecules in the early phase of drug discovery can be challenging; the presence of impurities in the target molecular entity can influence the quality, safety, and efficacy. An orthogonal method in analytical separation is a useful tool to ensure the specificity of the primary method. It enhances the probabilities to detect and quantify even the lowest amount of impurity that may be present in the sample. It ensures there is no co-elution of the impurity with the degradation compounds and with the active peak. This review article emphasizes and summarizes the need for an orthogonal method in chromatographic separations for pharmaceutical analysis. It enlists strategies that can be adopted for the development of an orthogonal method and the various advances in the metrics for orthogonality. The geometric approach, hydrogen subtraction model, system selectivity cube, linear solvation energy relationship, non-parametric approach and computer-assisted method development for selection of similar or orthogonal columns are discussed in detail.