Automated Liquid Chromatography-Mass Spectrometry Methods for Forced Degradation Studies

Abdul Khalek, Albaraa N., Sabina Kurtovic, Kayla C. Lapworth, Kaitlan F. Vossen, Shahad Zoma, and Kendra R. Evans

Forced degradation studies are widely used in the pharmaceutical industry to investigate the degradation pathways of drugs to indicate their stability.  Forced degradation reactions are often monitored by stability-indicating assays using liquid chromatography-mass spectrometry (LC-MS), which enables the quantitation of reactants, intermediates, and degradation products and aids in the identification of unknown species.  We have developed a simple instrument for online monitoring of forced degradation reactions that can be adapted to any commercial LC-MS equipment.  The system allows automated, continuous sampling of reaction mixtures by low flow rate vacuum aspiration followed by continuous, computer-controlled injections for online LC-MS analysis.  The stability of the automated sampling and injection system is excellent, with 3% relative standard deviation in peak area over a 24-h period.  The automated LC-MS method was used to examine the forced degradation of a common antiseptic, chlorhexidine, for 24 h with 15-min temporal resolution.  Additionally, a stability-indicating assay for the new-to-the-market cancer drug, palbociclib, was developed and will be presented.