Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS

Area of Science:

• Pharmacology
• Nanotechnology
• Analytical Chemistry

Background:

• Olaparib is a PARP inhibitor crucial for treating BRCA-mutated breast cancers.
• Olaparib exhibits poor solubility and low bioavailability, limiting its therapeutic efficacy.
• Nano-delivery systems offer a promising strategy to enhance Olaparib's pharmacokinetic profile.

Purpose of the Study:

• To develop and validate a sensitive HPLC-ESI⁻MS/MS method for quantifying Olaparib.
• To assess the impact of ferritin nano-carriers on Olaparib's distribution in various biological matrices.
• To evaluate Olaparib release kinetics from nano-carriers for improved drug development.

Main Methods:

• High-Performance Liquid Chromatography coupled with Electrospray Ionization-Tandem Mass Spectrometry (HPLC-ESI⁻MS/MS) was employed for Olaparib quantification.
• The method was validated across diverse matrices including cell compartments (cytoplasm, nuclei), plasma, urine, and tissues (kidney, liver).
• Ferritin nano-carriers were utilized for Olaparib encapsulation and delivery studies in BRCA-mutated cell models.

Main Results:

• The validated HPLC-ESI⁻MS/MS method demonstrated high sensitivity and robustness with specific linear ranges for different matrices.
• Quantification limits were established, with values as low as 0.48 ng/mL for certain matrices.
• The method successfully quantified Olaparib distribution in cellular compartments and tissues, revealing the effects of nano-encapsulation.

Conclusions:

• The developed HPLC-ESI⁻MS/MS method is suitable for quantifying Olaparib in ferritin nano-carriers and various biological samples.
• Nano-delivery significantly influences Olaparib's distribution, offering potential for improved therapeutic outcomes.
• This analytical approach is essential for validating nano-carrier performance and optimizing drug release profiles.