Preliminary results using a kit to measure tamoxifen and metabolites concentrations in capillary blood samples from women with breast cancer

Stefan Rehnmark,Håkan Randahl,Yvonne Wengström,Ivan Shabo,Per Rydberg,Elham Hedayati

doi:10.1038/s41598-022-05443-0

Stefan Rehnmark, Håkan Randahl + Show 4 more

Open Access

https://doi.org/10.1038/s41598-022-05443-0

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Abstract

The aim of the study was to compare 3 blood sampling methods, including capillary blood sampling, for determining Tamoxifen (TAM), Z-endoxifen (END), and 4-hydroxytamoxifen (4HT) concentrations. High performance liquid chromatography-mass spectrometry was used to quantify concentrations of TAM, END, and 4HT in plasma, venous blood, and capillary blood samples of 16 participants on TAM therapy for breast cancer. The rhelise kit was used for capillary sampling. Calibration curves using 13C-labeled analogs of TAM, END, and 4HT as internal standards were used for quantifications. A capillary sampling kit was used successfully for all participants. Mean TAM concentrations did not differ significantly in the 3 types of samples. Mean END and 4HT concentrations did differ significantly between capillary and venous blood samples, possibly related to photodegradation in the internal standards prior to use or degradation products with chromatographic retention times similar to the metabolites. TAM, END, and 4HT concentrations were relatively stable when stored for 14 days at 8 °C and 20 °C. Therapeutic drug monitoring of TAM using an innovative kit and capillary blood sampling is feasible. Preliminary data from this study will aid in developing a multicenter, randomized clinical trial of personalized TAM dose monitoring and adjustments, with the goal of enhancing the quality-of-life and outcomes of patients with breast cancer.Clinical Trial Identification: EudraCT No 2017-000641-44.

Highlights

The aim of the study was to compare 3 blood sampling methods, including capillary blood sampling, for determining Tamoxifen (TAM), Z-endoxifen (END), and 4-hydroxytamoxifen (4HT) concentrations
Venous blood, and capillary blood samples were collected from all 16 participants at the same time by a trained research nurse
The ratio of plasma to venous blood TAM concentrations was determined for each participant; the mean plasma-to-blood TAM ratio for the group was 0.914 (Standard Deviation [standard deviations (SD)], 0.108; Standard Error of Mean [standards of the mean (SEM)], 0.027) (Fig. 1b)

Summary

Introduction

The aim of the study was to compare 3 blood sampling methods, including capillary blood sampling, for determining Tamoxifen (TAM), Z-endoxifen (END), and 4-hydroxytamoxifen (4HT) concentrations. Mean END and 4HT concentrations did differ significantly between capillary and venous blood samples, possibly related to photodegradation in the internal standards prior to use or degradation products with chromatographic retention times similar to the metabolites. Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) that inhibits estrogen receptor (ER) transcriptional activity by binding to estrogen receptors It is commonly used as adjuvant monotherapy to treat hormone-receptor (HR)-positive breast cancer (BC) in premenopausal women and as part of sequential therapy to treat BC in postmenopausal women. There are no routine therapeutic monitoring tests used for TAM or its active metabolites Such tests, if administered, could be useful in addressing the discontinuation, noncompliance, and adverse effect issues involving TAM therapy. TAM and its metabolites could aid in identifying potentially modifiable factors contributing to adverse effects, including liver function abnormalities, polymorphisms in pertinent cytochrome P450 (CYP450) enzymes, and drug-drug interactions

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