Therapeutic drug monitoring in breast cancer therapy - LC-MS/MS method for quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, ribociclib, and major metabolites abemaciclib M20 and M2 in human serum
Source : https://www.sciencedirect.com/science/article/abs/pii/S073170852200632X?via=ihub
Quantification of CDK4/6 inhibitors by semi-automated sample preparation and LC-MS/MS. * Method validation according to FDA including long-term stability up to one year. * TDM of oral tumor therapeutics in breast cancer therapy for personalized medicine. The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib, ribociclib, and abemaciclib were approved by the U.S.
Conclusions: This novel semi-automated LC-MS/MS method covering all previously approved CDK4/6 inhibitors as well as the similarly pharmacologically active metabolites in human serum simultaneously was developed for potential future use in routine analysis in order to improve
• Source: Journal of Pharmaceutical and Biomedical Analysis
• Relevance: “The aim of the present work was to establish a semi-automated liquid-chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of abemaciclib, its active metabolites abemaciclib M20 and M2, palbociclib, and ribociclib in human serum. Detuning of ribociclib enabled the development of a simultaneous quantification method for abemaciclib, M20, M2, palbociclib, and ribociclib in the respective relevant concentration ranges based on semi-automated sample preparation with isotope dilution LC-MS/MS.”
• Researchers validated this method according to FDA guidance and demonstrated inaccuracies of ≤ 10.7% and imprecisions ≤ %.
• According to the researchers, linearity was given from 20 to 800 ng/mL for abemaciclib, 15–600 ng/mL for M20, 10–400 ng/mL for M2/palbociclib, and 100–4000 ng/mL for ribociclib.
• The intention of this technology is to improve therapeutic drug monitoring in a move toward personalized medicine.