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Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen
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Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen
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Journal Article
Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen
2014
Overview
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.
Publisher
Springer US,Springer,Springer Nature B.V
