Lieve Dillen1, Luc Sips1, Tony Greway2, Tom Verhaeghe1. 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.
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.
Authors: François Halloy; Pavithra S Iyer; Paulina Ćwiek; Alice Ghidini; Jasmin Barman-Aksözen; Nicole Wildner-Verhey van Wijk; Alexandre P A Theocharides; Elisabeth I Minder; Xiaoye Schneider-Yin; Daniel Schümperli; Jonathan Hall Journal: Nucleic Acids Res Date: 2020-05-21 Impact factor: 16.971