Quantitative determination of total and unbound paclitaxel in human plasma following Abraxane treatment

Erin R. Gardner, William Dahut, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

A simple, rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantification of both unbound and total paclitaxel in plasma following treatment with Abraxane (ABI-007) or Taxol. Accurate and reproducible analysis of ABI-007, an albumin nanoparticle formulation of paclitaxel could not be achieved using previously published methodology designed for Taxol. The final validated method involved protein precipitation followed by vacuum filtration, in a 96-well format for rapid processing. The 4 min run employed gradient elution on a Waters SymmetryShield C8 (2.1 mm × 50 mm, 3.5 μm) column, followed by tandem mass spectrometric detection, in electrospray positive mode. Calibrator samples were prepared daily with paclitaxel and analyzed with both ABI-007 and paclitaxel quality control samples. To measure unbound drug, sample preparation was preceded by ultrafiltration. The assay was linear over the range of 10-2500 ng/mL, with dilution providing measurement up to 50,000 ng/mL. Within-run and between-run precision for all QC samples was less than 5.0% and 10.4%, respectively. Accuracy was high, with deviation of less than 6.1% for all QCs. Measurement of unbound paclitaxel was precise (BRP and WRP <10%).

Original languageEnglish
Pages (from-to)213-218
Number of pages6
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume862
Issue number1-2
DOIs
StatePublished - 1 Feb 2008
Externally publishedYes

Keywords

  • Albumin
  • Anticancer
  • Formulation
  • Free fraction
  • LC-MS/MS
  • Nanoparticle
  • Paclitaxel
  • Taxane
  • Unbound fraction

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