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Automated solubility and crystallization analysis of non-UV active compounds: integration of evaporative light scattering detection (ELSD) and robotic sampling

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Abstract

This article describes the integration of evaporative light scattering detection (ELSD) with automated robotic sampling to obtain reliable and data-rich solubility and crystallization profiles of minimally- or non-UV active compounds. The new technology allowed for the thermodynamic solubilities of various compounds to be profiled over broad temperature ranges without experimenter intervention. Two case studies are presented that illustrate the ability of the automated system to furnish solution phase composition of systems actively undergoing crystallization: first, the dynamic change in the solution phase concentration of multiple components during seeded preferential crystallization is monitored and time-course profiles showing the change in solution phase enantiomeric excess (e.e.) were created. Second, a diastereomeric resolution is profiled, illustrating the utility that monitoring the solution phase composition during crystallization has on reporting on the success of this classical resolution method. Validation of the sampling technology is provided by corroborating the ELSD data with in situ ReactIR monitoring.

Graphical abstract: Automated solubility and crystallization analysis of non-UV active compounds: integration of evaporative light scattering detection (ELSD) and robotic sampling

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Publication details

The article was received on 01 Feb 2019, accepted on 04 Jun 2019 and first published on 05 Jun 2019


Article type: Paper
DOI: 10.1039/C9RE00057G
React. Chem. Eng., 2019, Advance Article

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    Automated solubility and crystallization analysis of non-UV active compounds: integration of evaporative light scattering detection (ELSD) and robotic sampling

    R. Chung and J. E. Hein, React. Chem. Eng., 2019, Advance Article , DOI: 10.1039/C9RE00057G

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