Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots--development, validation and clinical application during breast cancer adjuvant therapy.

Antunes, Marina Venzon;Raymundo, Suziane;de Oliveira, Vanessa;Staudt, Dilana Elisabeth;Linden, Rafael;et.al.
(2015) Talanta — Vol. 132, p. 775-784 (2015)

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Authors
  • Antunes, Marina Venzon
    Author
  • Raymundo, Suziane
    Author
  • de Oliveira, Vanessa
    Author
  • Staudt, Dilana Elisabeth
    Author
  • Tré-Hardy, MarieUCLouvain
    Author
  • Capron, ArnaudUCLouvain
    Author
  • Haufroid, Vincentorcid-logoUCLouvain
    Author
  • Wallemacq, PierreUCLouvain
    Author
  • Linden, Rafael
    Author
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Abstract
A LC-MSMS method for the simultaneous determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots samples was developed and validated. The method employs an ultrasound-assisted liquid extraction and a reversed phase separation in an Acquity(®) C18 column (150×2.1 mm, 1.7 µm). Mobile phase was a mixture of formic acid 0.1% (v/v) pH 2.7 and acetonitrile (gradient from 60:40 to 50:50, v/v). Total analytical run time was 8 min. Precision assays showed CV % lower than 10.75% and accuracy in the range 94.5 to 110.3%. Mean analytes recoveries from DBS ranged from 40% to 92%. The method was successfully applied to 91 paired clinical DBS and plasma samples. Dried blood spots concentrations were highly correlated to plasma, with rs>0.83 (P<0.01). Median estimated plasma concentrations after hematocrit and partition factor adjustment were: TAM 123.3 ng mL(-1); NDT 267.9 ng mL(-1), EDF 10.0 ng mL(-1) and HTF 1.3 ng mL(-1,) representing in average 98 to 104% of the actually measured concentrations. The DBS method was able to identify 96% of patients with plasma EDF concentrations below the clinical threshold related to better prognosis (5.9 ng mL(-1)). The procedure has adequate analytical performance and can be an efficient tool to optimize adjuvant breast cancer treatment, especially in resource limited settings.
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Antunes, M. V., Raymundo, S., de Oliveira, V., Staudt, D. E., Gössling, G., Peteffi, G. P., Biazús, J. V., Cavalheiro, J. A., Tré-Hardy, M., Capron, A., Haufroid, V., Wallemacq, P., Schwartsmann, G., & Linden, R. (2015). Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots--development, validation and clinical application during breast cancer adjuvant therapy. Talanta, 132, 775-784. https://doi.org/10.1016/j.talanta.2014.10.040 (Original work published 2015)