New UPLC-MS/MS Assay for the Determination of Tamoxifen and Its Metabolites in Human Plasma, Application to Patients

Overview

Journal Future Sci OA

Specialty Biotechnology

Date 2019 Jun 28

PMID 31245038

Citations 5

Authors

Christine Bobin-Dubigeon

Mario Campone

Elsa Rossignol

Estelle Salaun

Marie-Bernadette Amiand

Jean-Marie Bard

Affiliations

Soon will be listed here.

Abstract

Aim: A rapid UPLC-MS/MS method for the determination of tamoxifen (TAM), -desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in human plasma was validated, after a simple protein precipitation.

Materials And Methods: The analysis was achieved on a C analytical column, using a gradient elution with a mobile phase of water and acetonitrile for 4.5 min.

Results: The validated method demonstrated good linearity between 1 and 500 ng/ml for TAM and -desmethyltamoxifen; between 0.2 and 100 ng/ml for endoxifen and between 0.1 and 50 ng/ml for 4-hydroxytamoxifen. The method also provided satisfactory results in terms of within day and between day imprecisions and accuracy, and also in terms of time stability and specificity.

Conclusion: The method is applied routinely for TAM monitoring from patients undergoing therapy.

Citing Articles

Long-Term Oral Tamoxifen Administration Decreases Brain-Derived Neurotrophic Factor in the Hippocampus of Female Long-Evans Rats.

Been L, Halliday A, Blossom S, Bien E, Bernhard A, Roth G Cancers (Basel). 2024; 16(7).

PMID: 38611051 PMC: 11010888. DOI: 10.3390/cancers16071373.

Enhancing Solid-Phase Extraction of Tamoxifen and Its Metabolites from Human Plasma Using MOF-Integrated Polyacrylonitrile Composites: A Study on CuBTC and ZIF-8 Efficacy.

Flores-Hernandez D, Leija Gutierrez H, Hernandez-Hernandez J, Sanchez-Fernandez J, Bonilla-Rios J Nanomaterials (Basel). 2024; 14(1).

PMID: 38202528 PMC: 10780427. DOI: 10.3390/nano14010073.

Steroid profile in patients with breast cancer and in mice treated with mifepristone.

Elia A, Saldain L, Lovisi S, Martinez Vazquez P, Burruchaga J, Lamb C Endocr Relat Cancer. 2023; 31(2).

PMID: 37962553 PMC: 10762537. DOI: 10.1530/ERC-23-0238.

Targeting hormone-resistant breast cancer cells with docetaxel: a look inside the resistance.

Scherbakov A, Basharina A, Sorokin D, Mikhaevich E, Mizaeva I, Mikhaylova A Cancer Drug Resist. 2023; 6(1):103-115.

PMID: 37065867 PMC: 10099602. DOI: 10.20517/cdr.2022.96.

Real-time bioelectronic sensing of environmental contaminants.

Atkinson J, Su L, Zhang X, Bennett G, Silberg J, Ajo-Franklin C Nature. 2022; 611(7936):548-553.

PMID: 36323787 DOI: 10.1038/s41586-022-05356-y.

References

Lee K, Ward B, Desta Z, Flockhart D, Jones D . Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 791(1-2):245-53. DOI: 10.1016/s1570-0232(03)00218-6. View

Stearns V, Johnson M, Rae J, Morocho A, Novielli A, Bhargava P . Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003; 95(23):1758-64. DOI: 10.1093/jnci/djg108. View

Johnson M, Zuo H, Lee K, Trebley J, Rae J, Weatherman R . Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat. 2004; 85(2):151-9. DOI: 10.1023/B:BREA.0000025406.31193.e8. View

Desta Z, Ward B, Soukhova N, Flockhart D . Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004; 310(3):1062-75. DOI: 10.1124/jpet.104.065607. View

Gjerde J, Kisanga E, Hauglid M, Holm P, Mellgren G, Lien E . Identification and quantification of tamoxifen and four metabolites in serum by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2005; 1082(1):6-14. DOI: 10.1016/j.chroma.2005.01.004. View

Viswanathan C, Bansal S, Booth B, DeStefano A, Rose M, Sailstad J . Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays. Pharm Res. 2007; 24(10):1962-73. DOI: 10.1007/s11095-007-9291-7. View

Nowatzke W, Woolf E . Best practices during bioanalytical method validation for the characterization of assay reagents and the evaluation of analyte stability in assay standards, quality controls, and study samples. AAPS J. 2007; 9(2):E117-22. PMC: 2751400. DOI: 10.1208/aapsj0902013. View

Jordan V . New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer. Steroids. 2007; 72(13):829-42. PMC: 2740485. DOI: 10.1016/j.steroids.2007.07.009. View

Teunissen S, Rosing H, Koornstra R, Linn S, Schellens J, Schinkel A . 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. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(24):2519-29. DOI: 10.1016/j.jchromb.2009.06.029. View

10.

Hughes N, Bajaj N, Fan J, Wong E . Assessing the matrix effects of hemolyzed samples in bioanalysis. Bioanalysis. 2010; 1(6):1057-66. DOI: 10.4155/bio.09.91. View

11.

Dahmane E, Mercier T, Zanolari B, Cruchon S, Guignard N, Buclin T . An ultra performance liquid chromatography-tandem MS assay for tamoxifen metabolites profiling in plasma: first evidence of 4'-hydroxylated metabolites in breast cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878(32):3402-14. DOI: 10.1016/j.jchromb.2010.10.027. View

12.

Ochoa Aranda E, Esteve-Romero J, Rambla-Alegre M, Peris-Vicente J, Bose D . Development of a methodology to quantify tamoxifen and endoxifen in breast cancer patients by micellar liquid chromatography and validation according to the ICH guidelines. Talanta. 2011; 84(2):314-8. DOI: 10.1016/j.talanta.2011.01.022. View

13.

Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt S . Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011; 89(5):718-25. PMC: 3081375. DOI: 10.1038/clpt.2011.32. View

14.

Freedman A, Yu B, Gail M, Costantino J, Graubard B, Vogel V . Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011; 29(17):2327-33. PMC: 3107748. DOI: 10.1200/JCO.2010.33.0258. View

15.

Teunissen S, Jager N, Rosing H, Schinkel A, Schellens J, Beijnen J . Development and validation of a quantitative assay for the determination of tamoxifen and its five main phase I metabolites in human serum using liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011; 879(19):1677-85. DOI: 10.1016/j.jchromb.2011.04.011. View

16.

Binkhorst L, Mathijssen R, Ghobadi Moghaddam-Helmantel I, de Bruijn P, van Gelder T, Wiemer E . Quantification of tamoxifen and three of its phase-I metabolites in human plasma by liquid chromatography/triple-quadrupole mass spectrometry. J Pharm Biomed Anal. 2011; 56(5):1016-23. DOI: 10.1016/j.jpba.2011.08.002. View

17.

Sestak I, Kealy R, Nikoloff M, Fontecha M, Forbes J, Howell A . Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial. Br J Cancer. 2012; 107(2):230-3. PMC: 3394993. DOI: 10.1038/bjc.2012.278. View

18.

Antunes M, Dornelles Rosa D, Viana T, Andreolla H, Fontanive T, Linden R . Sensitive HPLC-PDA determination of tamoxifen and its metabolites N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in human plasma. J Pharm Biomed Anal. 2013; 76:13-20. DOI: 10.1016/j.jpba.2012.12.005. View

19.

Kiyotani K, Mushiroda T, Zembutsu H, Nakamura Y . Important and critical scientific aspects in pharmacogenomics analysis: lessons from controversial results of tamoxifen and CYP2D6 studies. J Hum Genet. 2013; 58(6):327-33. DOI: 10.1038/jhg.2013.39. View

20.

Cronin-Fenton D, Damkier P, Lash T . Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2013; 10(1):107-22. PMC: 4319217. DOI: 10.2217/fon.13.168. View