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

Author:

Dillen Lieve1,Sips Luc1,Greway Tony2,Verhaeghe Tom1

Affiliation:

1. Development Bioanalysis, Janssen Research & Development, 2340 Beerse, Belgium

2. Preclinical Development & Safety, Janssen Research & Development, Raritan, NJ 08869, USA

Abstract

Aim: Imetelstat, a 13-mer oligonucleotide with a lipid tail is being evaluated for treating hematologic myeloid malignancies. This report describes the development of extraction and quantification methods for imetelstat. Methodology & results: Imetelstat was extracted using SPE (rat plasma) or by hybridization using a biotinylated capture probe (human plasma) and was quantified by LC–MS/MS. Calibration curves were established (0.1–50 μg/ml). Stability of imetelstat in plasma was demonstrated. Concentrations of imetelstat extracted using either of the methods and quantified with LC–MS/MS were comparable with a validated ELISA. Conclusion: Two extraction methods (solid phase and hybridization) were developed for quantifying imetelstat in plasma using LC–MS/MS. The hybridization extraction in combination with LC–MS/MS is a novel extraction approach.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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