A fast and validated LC-MS/MS method to quantify lenvatinib in dried blood spot.

A new LC-MS/MS method for the quantification of lenvatinib (LENVA) in venous Dried Blood Spot (DBS) samples has been presented. This method is characterized by a short run time (4 min), requires a volumetric sampling of 10 µL and extraction of the entire spot to avoid hematocrit (Hct) and spot volume effects. The quantification method was successfully validated in the range of 5.00-2000 ng/mL on two different DBS filter papers (Whatman 31 ET CHR and Whatman 903) according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, European Bioanalysis Forum (EBF), and International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) recommendations. During the validation process, the following parameters were evaluated: recovery (≥ 77% for both filter papers), absence of matrix effect, process efficiency (close to 72% for Whatman 31 ET CHR and close to 77% for Whatman 903), Hct effect (CV ≤ 6.3% and accuracy within 96-112%), linearity (r ≥ 0.998 for Whatman 31 ET CHR and r ≥ 0.999 for Whatman 903), intra- and inter-day precision (CV ≤ 8.8%) and accuracy (92.8-108%), selectivity and sensitivity, reproducibility with incurred samples reanalysis (ISR), and stability. This method was applied to quantify venous DBS samples from patients with hepatocellular carcinoma treated with LENVA enrolled in a cross-validation study (CRO-2018-83). A good correlation between LENVA plasma concentration determined by standard procedure and the new developed DBS LENVA method (R

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Fabio Puglisi reports a relationship with Amgen that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with AstraZeneca that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Daichii Sankyo that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Celgene that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Eisai that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Eli Lilly that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Gilead that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Ipsen that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with MSD that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Novartis that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Pierre Fabre that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Pfizer that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Roche that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Seagen that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Takeda that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Fabio Puglisi reports a relationship with Viatris that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement.