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Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen

  • Clinical Trial
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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.

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Acknowledgments

We would like to acknowledge the assistance of the nurse practitioners of the Breast Cancer Clinic of the Netherlands Cancer Institute in patient recruitment. We would like to thank the staff of the Trial Laboratory of the Netherlands Cancer Institute for obtaining all patient samples.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands

    N. G. L. Jager, H. Rosing & J. H. Beijnen

  2. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    J. H. M. Schellens & J. H. Beijnen

  3. Department of Pharmaceutical Sciences, Faculty of Science, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands

    J. H. M. Schellens & J. H. Beijnen

  4. Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    S. C. Linn

  5. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    S. C. Linn

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  1. N. G. L. Jager
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  2. H. Rosing
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  3. J. H. M. Schellens
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  4. J. H. Beijnen
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  5. S. C. Linn
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Correspondence to N. G. L. Jager.

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Jager, N.G.L., Rosing, H., Schellens, J.H.M. et al. Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen. Breast Cancer Res Treat 146, 137–144 (2014). https://doi.org/10.1007/s10549-014-2999-2

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  • DOI: https://doi.org/10.1007/s10549-014-2999-2

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