Bibliographic Details
| Title: |
Quantification of Letrozole, Palbociclib, Ribociclib, Abemaciclib, and Metabolites in Volumetric Dried Blood Spots: Development and Validation of an LC-MS/MS Method for Therapeutic Drug Monitoring. |
| Authors: |
Cecchin, Eleonora, Orleni, Marco, Gagno, Sara, Montico, Marcella, Peruzzi, Elena, Roncato, Rossana, Gerratana, Lorenzo, Corsetti, Serena, Puglisi, Fabio, Toffoli, Giuseppe, Cecchin, Erika, Posocco, Bianca |
| Source: |
International Journal of Molecular Sciences; Oct2024, Vol. 25 Issue 19, p10453, 17p |
| Subject Terms: |
DRUG monitoring, INDUCTIVELY coupled plasma mass spectrometry, CYCLIN-dependent kinase inhibitors, MATRIX effect, MASS spectrometers |
| Abstract: |
Therapeutic drug monitoring (TDM) may be beneficial for cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), such as palbociclib, ribociclib, and abemaciclib, due to established exposure–toxicity relationships and the potential for monitoring treatment adherence. Developing a method for quantifying CDK4/6is, abemaciclib metabolites (M2, M20), and letrozole in dried blood spots (DBS) could be useful to enhance the feasibility of TDM. Thus, an optimized LC-MS/MS method was developed using the HemaXis DB10 device for volumetric (10 µL) DBS collection. Chromatographic separation was achieved using a reversed-phase XBridge BEH C18 column. Detection was performed with a triple quadrupole mass spectrometer, utilizing ESI source switching between negative and positive ionization modes and multiple reaction monitoring acquisition. Analytical validation followed FDA, EMA, and IATDMCT guidelines, demonstrating high selectivity, adequate sensitivity (LLOQ S/N ≥ 30), and linearity (r ≥ 0.997). Accuracy and precision met acceptance criteria (between-run: accuracy 95–106%, CV ≤ 10.6%). Haematocrit independence was confirmed (22–55%),with high recovery rates (81–93%) and minimal matrix effects (ME 0.9–1.1%). The stability of analytes under home-sampling conditions was also verified. Clinical validation supports DBS-based TDM as feasible, with conversion models developed for estimating plasma concentrations (the reference for TDM target values) of letrozole, abemaciclib, and its metabolites. Preliminary data for palbociclib and ribociclib are also presented. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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