Simple determination of plasma ibrutinib concentration using high-performance liquid chromatography

Area of Science:

• Pharmacology
• Analytical Chemistry
• Clinical Chemistry

Background:

• Ibrutinib is a crucial oral Bruton tyrosine kinase inhibitor for treating chronic lymphocytic leukemia and mantle cell lymphoma.
• Accurate monitoring of plasma ibrutinib concentrations is essential for effective therapeutic drug monitoring.
• Existing methods may lack the simplicity required for routine laboratory use.

Purpose of the Study:

• To develop and validate a straightforward method for quantifying ibrutinib in human plasma.
• To establish a reliable assay for therapeutic drug monitoring of ibrutinib.

Main Methods:

• Plasma samples (200 μL) were processed using solid-phase extraction.
• Ibrutinib and nilotinib (internal standard) were separated via high-performance liquid chromatography (HPLC).
• Detection was performed using UV at 260 nm with a specific mobile phase (acetonitrile-0.5% KH2PO4).

Main Results:

• The method demonstrated linearity over a 10-500 ng/mL range (r² = 0.9999).
• Intra-day and inter-day validation coefficients were within acceptable limits (4.0-6.6% and 2.6-7.7%).
• Assay accuracy ranged from -4.4% to 8.6%, with recovery exceeding 84%.

Conclusions:

• A simple and reliable HPLC-UV method for determining plasma ibrutinib concentration was successfully developed.
• This assay is well-suited for routine therapeutic drug monitoring in clinical hospital laboratories.
• The method offers advantages in simplicity and applicability for managing ibrutinib therapy.