Quantitative analysis of imetelstat in plasma with LC-MS/MS using solid-phase or hybridization extraction

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry

Background:

• Imetelstat is an oligonucleotide therapeutic candidate for hematologic myeloid malignancies.
• Accurate quantification of imetelstat in biological matrices is crucial for its clinical development.

Purpose of the Study:

• To develop and validate robust extraction and quantification methods for imetelstat in plasma.
• To compare the performance of novel extraction techniques with existing methods.

Main Methods:

• Imetelstat extraction from rat plasma utilized solid-phase extraction (SPE).
• Imetelstat extraction from human plasma employed a novel hybridization method with a biotinylated capture probe.
• Quantification was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Calibration curves ranged from 0.1 to 50 μg/ml, and imetelstat stability in plasma was confirmed.

Main Results:

• Both SPE and hybridization extraction methods, coupled with LC-MS/MS, provided reliable imetelstat quantification.
• The results obtained were comparable to those from a validated enzyme-linked immunosorbent assay (ELISA).

Conclusions:

• Two distinct methods for imetelstat plasma extraction (solid-phase and hybridization) were successfully developed and validated using LC-MS/MS.
• The hybridization-based extraction method represents a novel approach for imetelstat analysis.