Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry

Guowei Dai, Xiaohui Wei, Zhongfa Liu, Shujun Liu, Guido Marcucci, Kenneth K. Chan

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

A novel ion-pair reversed phase electrospray ionization (IP-RP-ESI) liquid chromatography-mass spectrometry (LC-MS) method has been developed for identification and quantification of Bcl-2 antisense phosphorothioate oligonucleotides G3139 and metabolites in plasma. This method utilized solid phase extraction for desalting and matrix removal and detection by an ion trap mass spectrometer. Resolution was accomplished on a micro C18 column eluted with a mobile phase consisting of hexafluoro-2-propanol and triethylamine in methanol at 50 °C. Five G3139 metabolites were identified in plasma and urine from treated patients and rats. A cassette HPLC-MS/MS quantification method for G3139 and three metabolites was developed and validated with a limit of quantification (LOQ) of 17.6 nM in human and rat plasma with acceptable precision and accuracy. Plasma pharmacokinetics of G3139 and metabolites in these species were described.

Original languageEnglish (US)
Pages (from-to)201-213
Number of pages13
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume825
Issue number2
DOIs
StatePublished - Oct 25 2005
Externally publishedYes

Bibliographical note

Funding Information:
We thank Drs. Jef Rozenski (Katholieke Universiteit Leuven, Belgium) and James A. McCloskey (University of Utah) for providing the SOS program used in this work. This research was supported in part by grants R21 CA94552 from the National Cancer Institute, the National Institute of Health and by BioMedical Mass Spectrometry Laboratory of College of Pharmacy.

Keywords

  • Bcl-2 antisense
  • Metabolism
  • N-in-one quantification
  • Pharmacokinetics
  • Tandem mass spectrometry

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