Bioanalysis of selinexor in mouse plasma micro-samples utilizing UPLC-MS/MS

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Oncology

Background:

• Selinexor, a first-in-class inhibitor of the nuclear export protein Exportin-1 (XPO1), has gained approval for treating multiple myeloma and diffuse large B-cell lymphoma.
• Preclinical studies are essential for understanding drug efficacy and safety profiles before human trials.

Purpose of the Study:

• To develop and validate a sensitive ultrahigh-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay for quantifying selinexor in mouse plasma.
• To establish a method suitable for small-volume plasma samples (5 µL) within a clinically relevant concentration range (1-1000 ng/mL).

Main Methods:

• Development of a UPLC-MS/MS assay utilizing positive electrospray ionization in selected reaction monitoring mode.
• Sample preparation involved protein precipitation with acetonitrile and a dilution step for efficient and scalable processing.
• Assay validation included assessment of accuracy and precision across interday and intraday runs.

Main Results:

• The UPLC-MS/MS assay demonstrated high sensitivity, suitable for plasma concentrations from 1-1000 ng/mL using only 5 µL of plasma.
• Validated accuracy ranged from 89.0% to 109.0%, with precision ≤ 14.1%.
• The assay's suitability was confirmed by measuring plasma selinexor concentrations in mice following oral administration.

Conclusions:

• A robust and sensitive UPLC-MS/MS assay for selinexor in mouse plasma has been successfully developed and validated.
• This assay enables precise pharmacokinetic investigations in small animal models, supporting the preclinical development of selinexor.
• The method's scalability and sensitivity allow for adaptation to different concentration ranges or reduced plasma volumes.