Development and validation of a quantitative assay for the analysis of tamoxifen with its four main metabolites and the flavonoids daidzein, genistein and glycitein in human serum using liquid chromatography coupled with tandem mass spectrometry.
The development and validation of a bioanalytical assay is described for the simultaneous analysis in human serum of tamoxifen, four of its main metabolites and three flavonoids, which are known constituents in alternative medicine and dietary supplements often used by breast cancer patients. The method has been fully validated at linear ranges covering steady-state serum concentrations in patients who receive therapeutic dosages of tamoxifen. The wide range also allows for quantification of large inter-patient fluctuations of flavonoid concentrations. The bioanalytical assay is based on reversed phase liquid chromatography coupled with tandem mass spectrometry in the positive ion mode using multiple reaction monitoring for drug (-metabolite) quantification. The sample pretreatment consists of a protein precipitation with acetonitrile using only 50 microL serum. The described method is simple, robust and reproducible with inter- and intra-assay accuracies within 85-115%. The applicability of the assay was demonstrated and it is now successfully used to study the in vivo pharmacokinetics of tamoxifen, its main metabolites and flavonoids in human serum of patients receiving tamoxifen.
Teunissen
S F
SF
Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. bas.teunissen@slz.nl
Rosing
H
H
Koornstra
R H T
RH
Linn
S C
SC
Schellens
J H M
JH
Schinkel
A H
AH
Beijnen
J H
JH
D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D007529:Isoflavones / Q000097:blood*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D013629:Tamoxifen / Q000097:blood* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000970:Antineoplastic Agents; D007529:Isoflavones; D013629:Tamoxifen