title: Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen.
abstract: The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and (Z)-endoxifen to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. Paired DBS and serum samples were obtained from 50 patients using tamoxifen and analyzed using HPLC-MS/MS. Serum concentrations were calculated from DBS concentrations using the formula calculated serum concentration = DBS concentration/([1-haematocrit (Hct)] + blood cell-to-serum ratio × Hct). The blood cell-to-serum ratio was determined ex vivo by incubating a batch of whole blood spiked with both analytes. The average Hct for female adults was imputed as a fixed value. Calculated and analyzed serum concentrations were compared using weighted Deming regression. Weighted Deming regression analysis comparing 44 matching pairs of DBS and serum samples showed a proportional bias for both analytes. Serum concentrations were calculated using [Tamoxifen] serum, calculated  = [Tamoxifen] DBS /0.779 and [(Z)-Endoxifen] serum, calculated = [(Z)-Endoxifen] DBS /0.663. Calculated serum concentrations were within 20 % of analyzed serum concentrations in 84 and 100 % of patient samples for tamoxifen and (Z)-endoxifen, respectively. In conclusion, DBS concentrations of tamoxifen and (Z)-endoxifen were equal to serum concentrations after correction for Hct and blood cell-to-serum ratio. DBS sampling can be used in clinical practice.
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands, Nynke.Jager@slz.nl.
authors.forename: N G L
authors.initials: NG
authors.lastname: Jager
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008875:Middle Aged; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen