A HPLC-mass spectrometric method suitable for the therapeutic drug monitoring of everolimus

Taylor, Paul J., Franklin, Michael E., Graham, Kendon S. and Pillans, Peter I. (2007) A HPLC-mass spectrometric method suitable for the therapeutic drug monitoring of everolimus. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 848 2: 208-214. doi:10.1016/j.jchromb.2006.10.029


Author Taylor, Paul J.
Franklin, Michael E.
Graham, Kendon S.
Pillans, Peter I.
Title A HPLC-mass spectrometric method suitable for the therapeutic drug monitoring of everolimus
Journal name Journal of chromatography. B, Analytical technologies in the biomedical and life sciences   Check publisher's open access policy
ISSN 1570-0232
Publication date 2007-04-01
Year available 2007
Sub-type Article (original research)
DOI 10.1016/j.jchromb.2006.10.029
Volume 848
Issue 2
Start page 208
End page 214
Total pages 7
Place of publication Amsterdam
Publisher Elsevier
Language eng
Subject 060101 Analytical Biochemistry
Abstract We report here the validation of an HPLC-electrospray-tandem mass spectrometry method for the quantification of everolimus, an immunosuppressant drug. Whole blood samples (100 mu L) were extracted by protein precipitation which involved sample pre-treatment with zinc sulphate followed by acetonitrile (containing internal standard, 40-O-(3'-hydroxy)propyl-rapamycin). HPLC was performed using a step-gradient at a flow rate of 0.6 ml/min on a Waters TDM C-18 column (10 mm x 2.1 mm I.D.) with a resultant chromatographic analysis time of 2 min. Mass spectrometric detection by selected reaction monitoring (everolimus m/z 975.5 -> 908.3; internal standard m/z 989.5 -> 922.3). The assay was linear from 0.5 to 40 mu g/l (r(2) > 0.994, n = 11). The inter- and intra-day analytical recovery and imprecision for quality control samples (1.25, 12.5 and 30 mu g/l) were 93.4-98.2% and <10.7%, respectively (n = 10). At the lower limit of quantification (0.5 mu g/l) the inter- and intra-day analytical recovery was 94.4-95.8% with imprecision of <14.1% (n=10). The absolute recovery of everolimus (6.5 mu g/l]) and internal standard (12.5 mu g/l) was 96.5 and 88.3%, respectively (n = 3). A comparison of our method against the mean of all HPLC methods for a series of samples from an external proficiency testing scheme revealed good correlation as shown by the regression analysis: y = 0.973x + 0.301 (r(2) = 0.986, n = 71). In conclusion, the method described is suited to the current requirements for therapeutic drug monitoring of everolimus. (c) 2006 Elsevier B.V. All rights reserved.
Keyword Biochemical Research Methods
Chemistry, Analytical
everolimus
transplantation
HPLC
mass spectrometry
therapeutic drug monitoring
Performance Liquid-chromatography
Exposure-response Relationships
Novo Kidney-transplantation
Ultraviolet Detection
Organ-transplantation
Concentration Range
Whole-blood
Cyclosporine
Immunosuppressants
Pharmacokinetics
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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