Automated R workflow for Batman peak fitting using unified equation and stochastic modeling

Area of Science:

• Analytical Chemistry
• Chemical Kinetics
• Pharmaceutical Sciences

Background:

• Chiral drugs exhibit enantiomers with differing pharmacological effects, necessitating accurate kinetic analysis.
• Chromatographic "Batman peaks" provide crucial data on on-column enantiomeric interconversion dynamics.

Purpose of the Study:

• To develop an automated R framework for extracting kinetic and thermodynamic constants from chromatographic data.
• To validate the framework's accuracy and flexibility across various chromatographic conditions.

Main Methods:

• Integration of the unified equation and a stochastic model within an automated R workflow.
• Application of robust optimization algorithms for accelerated and accurate data fitting.
• Analysis of Quetiapine chromatograms under varied flow rates and temperatures.

Main Results:

• Consistent rate constants obtained from both unified and stochastic models, aligning with optical rotation experiments.
• The stochastic model demonstrated applicability even with coalesced peaks.
• Determination of thermodynamic parameters via linearized Eyring-Polányi analysis.

Conclusions:

• The developed R framework offers a robust, flexible, and customizable platform for enantiomerization kinetics determination.
• Combining unified and stochastic modeling ensures reliable results across diverse chromatographic conditions.
• The framework is suitable for routine analysis of dynamic enantiomerization in pharmaceutical and analytical chemistry.