Next Article in Journal
Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy
Previous Article in Journal
Physico-Chemical Characterization and Initial Evaluation of Carboxymethyl Chitosan–Hyaluronan Hydrocolloid Systems with Insulin Intended for Intranasal Administration
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Eleonora Cecchin
1,
Marco Orleni
1,2,
Sara Gagno
1,
Marcella Montico
3,
Elena Peruzzi
1,
Rossana Roncato
1,
Lorenzo Gerratana
4,5,
Serena Corsetti
4,
Fabio Puglisi
4,5,
Giuseppe Toffoli
1,
Erika Cecchin
1,* and
Bianca Posocco
1
1
Experimental and Clinical Pharmacology Unit- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
2
Doctoral School in Pharmacological Sciences, University of Padua, 35131 Padova, Italy
3
Clinical Trial Office, Scientific Direction- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
4
Department of Medical Oncology- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
5
Department of Medicine, University of Udine, 33100 Udine, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(19), 10453; https://doi.org/10.3390/ijms251910453
Submission received: 7 August 2024 / Revised: 23 September 2024 / Accepted: 24 September 2024 / Published: 27 September 2024

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.
Keywords: palbociclib; ribociclib; abemaciclib; letrozole; therapeutic drug monitoring; mass spectrometry; dried blood spot; plasma exposure; Ctrough palbociclib; ribociclib; abemaciclib; letrozole; therapeutic drug monitoring; mass spectrometry; dried blood spot; plasma exposure; Ctrough

Share and Cite

MDPI and ACS Style

Cecchin, E.; Orleni, M.; Gagno, S.; Montico, M.; Peruzzi, E.; Roncato, R.; Gerratana, L.; Corsetti, S.; Puglisi, F.; Toffoli, G.; et al. 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. Int. J. Mol. Sci. 2024, 25, 10453. https://doi.org/10.3390/ijms251910453

AMA Style

Cecchin E, Orleni M, Gagno S, Montico M, Peruzzi E, Roncato R, Gerratana L, Corsetti S, Puglisi F, Toffoli G, et al. 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. International Journal of Molecular Sciences. 2024; 25(19):10453. https://doi.org/10.3390/ijms251910453

Chicago/Turabian Style

Cecchin, Eleonora, Marco Orleni, Sara Gagno, Marcella Montico, Elena Peruzzi, Rossana Roncato, Lorenzo Gerratana, Serena Corsetti, Fabio Puglisi, Giuseppe Toffoli, and et al. 2024. "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" International Journal of Molecular Sciences 25, no. 19: 10453. https://doi.org/10.3390/ijms251910453

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop