Quantification of cabazitaxel in human plasma by liquid chromatography/triple-quadrupole mass spectrometry: a practical solution for non-specific binding

J Pharm Biomed Anal. 2012 Feb 5;59:117-22. doi: 10.1016/j.jpba.2011.10.010. Epub 2011 Oct 24.

Abstract

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of cabazitaxel, a novel tubulin-binding taxane, in 100 μl aliquots of human lithium heparinized plasma with deuterated cabazitaxel as internal standard. The sample extraction and cleaning-up involved a simple liquid-liquid extraction with 20 μl aliquots of 4% ammonium hydroxide, 100 μl aliquots of acetonitrile and 1 ml aliquots of n-butylchloride. Chromatographic separations were achieved on a reversed phase C₁₈ column eluted at a flow-rate of 0.20 ml/min on a gradient of acetonitrile. The overall cycle time of the method was 5 min, with cabazitaxel eluting at 3.0 min. The multiple reaction monitoring transitions were set at 836>555 (m/z), and 842>561 (m/z) for cabazitaxel and the internal standard, respectively. The calibration curves were linear over the range of 1.00-100 ng/ml with the lower limit of quantitation validated at 1.00 ng/ml. The within-run and between-run precisions, also at the level of the LLQ, were within 8.75%, while the accuracy ranged from 88.5 to 94.1%. As dilution of samples prior to extraction resulted in a loss of cabazitaxel of approximately 6.5% per dilution step, a second calibration curve ranging from 40.0 to 4000 ng/ml was validated and was also linear. The within-run and between-run precisions in this range were within 4.99%, while the accuracy ranged from 95.8 to 100.3%. The method was successfully applied to samples derived from a clinical study.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / chemistry
  • Calibration
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods*
  • Dose-Response Relationship, Drug
  • Drug Stability
  • Humans
  • Infusions, Intravenous
  • Limit of Detection
  • Molecular Structure
  • Reference Standards
  • Reproducibility of Results
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods*
  • Taxoids / administration & dosage
  • Taxoids / blood*
  • Taxoids / chemistry

Substances

  • Antineoplastic Agents
  • Taxoids
  • cabazitaxel