Senior Scientist Bristol-Myers Squibb Princeton, New Jersey
Recently, 1β-hydroxydeoxycholic acid (1β-OH DCA) in human plasma has been explored as an alternative to 4β-hydroxycholesterol for assessment of CYP3A DDI potential. However, the accurate quantitation of 1β-OH DCA and its glycine and taurine conjugates using LC-MS/MS represents a significant challenge due to difficulty in resolving closely related positional isomers originating from the varying locations, and orientations of hydroxyl groups. Therefore, in this work, the use of supercritical fluid chromatography-mass spectrometry (SFC-MS/MS) was explored for the separation and quantitation of 1β-OH DCA and its glycine/taurine conjugates in human plasma. Our preliminary results show that chiral SFC-MS/MS can offer equivalent or even better resolution of these positional isomers, while achieving higher throughput compared to the LC-MS/MS method. In addition, we established a good correlation between SFC-MS/MS and LC-MS/MS for study sample analysis.
Learning Objectives:
Upon completion, participants will be able to explore the use of 1β-hydroxydeoxycholic acid and its conjugates as biomarkers of CYP3A DDI.
Upon completion, participants will be able to differentiate between supercritical fluid chromatography and liquid chromatography to identify which bioanalytical applications would benefit from using SFC.
Upon completion, participants will be able to utilize SFC-MS/MS for the challenging separation of 1β-hydroxydeoxycholic acid and its conjugates from their multiple positional isomers in human plasma.
