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

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Clinical Diagnostics

Background:

• Lenvatinib (LENVA) is a targeted therapy used for hepatocellular carcinoma.
• Accurate quantification of LENVA is crucial for therapeutic drug monitoring.
• Dried blood spot (DBS) sampling offers advantages over traditional plasma sampling.

Purpose of the Study:

• To develop and validate a novel LC-MS/MS method for quantifying lenvatinib (LENVA) in venous dried blood spot (DBS) samples.
• To assess the method's suitability for routine clinical use and therapeutic drug monitoring.
• To evaluate the method's performance against established guidelines and recommendations.

Main Methods:

• A sensitive LC-MS/MS assay was developed for LENVA quantification in DBS.
• Volumetric DBS sampling (10 µL) and whole spot extraction were employed.
• Method validation was performed according to EMA, FDA, EBF, and IATDMCT guidelines.

Main Results:

• The method demonstrated excellent linearity (r ≥ 0.998) over a wide quantification range (5.00–2000 ng/mL).
• High recovery (≥ 77%) and process efficiency were achieved, with minimal matrix and hematocrit effects.
• Intra- and inter-day precision (CV ≤ 8.8%) and accuracy (92.8–108%) were within acceptable limits.
• The method showed good reproducibility via incurred samples reanalysis (ISR) and stability.

Conclusions:

• A robust, validated LC-MS/MS method for LENVA quantification in DBS samples has been established.
• The method is suitable for therapeutic drug monitoring of lenvatinib in hepatocellular carcinoma patients.
• The developed DBS method correlates well with plasma concentrations, offering a convenient alternative for patient monitoring.