Determination of the heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin in plasma by liquid chromatography-electrospray mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):35-40. doi: 10.1016/j.jchromb.2005.10.019. Epub 2005 Nov 2.

Abstract

A rapid method was developed for the quantitative determination of the novel heat shock protein 90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG; NSC707545), in human plasma. Calibration curves were constructed, and were analyzed using a weight factor proportional to the nominal concentration. Sample pretreatment involved a one-step extraction with ethyl acetate of 0.5-ml samples. The analysis was performed in the range of 1-100 ng/ml on a column (75 mm x 2.1 mm internal diameter with 3.5 microm C18 particle size), using 55% methanol in water containing formic acid as the mobile phase. The column effluent was monitored by mass spectrometry with positive electrospray ionization. The values for precision and accuracy were always <8% and <10% relative error, respectively. The method was successfully applied to examine the pharmacokinetics of 17-DMAG in a cancer patient.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Benzoquinones
  • Chromatography, Liquid / methods*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Lactams, Macrocyclic
  • Quinones / blood*
  • Quinones / pharmacology
  • Reference Standards
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Quinones
  • 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin