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Analytical Performance of a New Liquid Chromatography/Tandem Mass Spectrometric Method for Determination of Everolimus Concentrations in Whole Blood

McMillin, Gwendolyn A. PhD*; Johnson-Davis, Kamisha PhD*; Dasgupta, Amitava PhD*


On page 223 of this article in the April 2012 issue, there was an error in stating: “High purity argon was used as the collision gas.” Nitrogen should have been listed as the collision gas. The author regrets this error.

Therapeutic Drug Monitoring. 34(4):485, August 2012.

doi: 10.1097/FTD.0b013e318246d515
Short Communication

The immunosuppressant everolimus was recently approved for prophylactic use in the United States, to prevent organ rejection in adult kidney transplant recipients. The currently accepted therapeutic range for everolimus is 3–8 ng/mL. Therapeutic drug monitoring (TDM) using predose EDTA whole blood samples is required to optimize dose. We describe a simple extraction method and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) to support routine TDM of everolimus. Samples were prepared by protein precipitation and filtration. The first quadrupole was set to select the ammonium adducts

of everolimus (m/z 975.62) and rapamycin-d3 (m/z 934.70), the internal standard. The second quadrupole was used as a collision chamber, and the third quadrupole was then used to select characteristic product ions of everolimus (m/z 908.50 and 890.50) and rapamycin-d3 (m/z 864.60 and 846.50). The method had an analytical measurement range of 2.0–150 ng/mL. Total imprecision, expressed as percent coefficient of variation (mean concentration), was 19.1% (3.3 ng/mL), 10.6% (5.9 ng/mL), 8.1% (19.2 ng/mL), 5.7% (25.8 ng/mL), and 9.1% (34.2 ng/mL). The new method was compared with 2 other everolimus methods also based on LC-MS/MS, with 64 residual patient specimens. Agreement, based on simple linear regression, was excellent. Method A comparison: y = 0.96x − 1.12 (r = 0.99), n = 20, 2.5–44.7 ng/mL. Method B comparison: y = 0.96x + 0.49 (r = 0.99), n = 44, 2.1–85.6 ng/mL. We conclude that this method could support TDM of everolimus for a wide range of clinical indications.

*Department of Pathology, University of Utah, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah

Department of Pathology and Laboratory Medicine, Houston Medical School, University of Texas, Houston, Texas.

The authors declare no conflict of interest.

Correspondence: Gwendolyn A. McMillin, PhD, Department of Pathology, University of Utah, ARUP Institute for Clinical and Experimental Pathology Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (e-mail:

Received September 29, 2011

Accepted December 15, 2011

© 2012 Lippincott Williams & Wilkins, Inc.