Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy

Steroids. 2007 Jul;72(8):666-71. doi: 10.1016/j.steroids.2007.05.003. Epub 2007 May 21.


Currently available radioimmunoassay methods for estradiol in serum lack sufficient sensitivity and precision to monitor estradiol levels in patients placed on third generation aromatase inhibitors. We recently validated a gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol and determined estrogen levels in normal post-menopausal women and in women with breast cancer before and during administration of aromatase inhibitors. Validation of the GC/MS/MS assay in human plasma and human serum included determination of assay sensitivity (<0.63 pg/ml), precision (all CVs less than 17.8%), recovery (98-103%), and linearity of recovery (R=0.998). Levels of estradiol were lower when assayed by GC/MS/MS compared to RIA under all conditions (7.26+/-4.82 pg/ml versus 11.9+12.0 pg/ml in normal post-menopausal women; 5.88+/-3.43 pg/ml versus 13.8+/-7.5 pg/ml in breast cancer patients prior to treatment; and<0.63 pg/ml versus 5.8+/-4.1 pg/ml during aromatase inhibitor therapy). Fifty-five women treated either with atamestane/toremiphene or letrozole/placebo were monitored for estradiol levels at 4, 8 and 12 weeks of therapy. The mean levels of estradiol during aromatase inhibitor therapy was 5.8+/-4.1 pg/ml as measured by RIA and <0.63 pg/ml by GC/MS/MS. The degree of suppression with the aromatase inhibitors as detected by RIA was 58% versus >89% by GC/MS. These results suggest that most RIA methods detect cross-reacting estrogen metabolites and yield higher measured levels than GC/MS/MS. Several pharmacological and clinical considerations suggest that GC/MS/MS should become the preferred method for monitoring aromatase inhibitor therapy.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Androstenedione / analogs & derivatives
  • Androstenedione / therapeutic use
  • Aromatase Inhibitors / therapeutic use*
  • Biological Assay
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Estradiol / blood*
  • Female
  • Gas Chromatography-Mass Spectrometry*
  • Humans
  • Letrozole
  • Nitriles / therapeutic use
  • Placebos
  • Postmenopause
  • Radioimmunoassay
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry*
  • Triazoles / therapeutic use


  • Aromatase Inhibitors
  • Nitriles
  • Placebos
  • Triazoles
  • Androstenedione
  • Estradiol
  • atamestane
  • Letrozole