Measurement of Tamoxifen and Endoxifen Concentrations via Liquid Chromatography-Tandem Mass Spectrometry to Assess Adherence and Optimal Concentrations in South Africans with Breast Cancer Participating in a Pilot Trial: A Short Communication

BACKGROUND: Breast cancer is a leading cause of cancer-related mortality in women globally. Breast cancer patients treated with tamoxifen demonstrate interpatient variability, with adherence challenges affecting up to 50% of patients by year 5, directly impacting the concentrations of the active metabolite of tamoxifen, namely endoxifen, and clinical outcomes. This pilot study evaluated the use of tamoxifen and endoxifen therapeutic drug monitoring (TDM) using liquid chromatography-tandem mass spectrometry in South African women. METHODS: The authors enrolled 20 women with estrogen receptor-positive breast cancer who were treated with tamoxifen; performed TDM on them, and assessed their adherence using objective and subjective methods. Objective nonadherence was defined as tamoxifen plasma concentration <60.0 ng/mL and subjective nonadherence was defined as self-reporting at least 1 missed dose. A Shimadzu LCMS-8040 instrument with an Agilent Poroshell 120 EC-C18 column was used to quantify tamoxifen and endoxifen plasma concentrations using protein precipitation extraction. RESULTS: The participants' mean age was 45 ± 9.92 years; most had stage 4 breast cancer and were prescribed tamoxifen for palliative treatment. Tamoxifen and endoxifen concentrations were 11.7-340 ng/mL (median of 136 ng/mL) and 3.64-34.2 ng/mL (median of 12.4 ng/mL), respectively. Objective nonadherence was low (5%), whereas subjective nonadherence was high (45%), with weak agreement (P = 0.322). Based on a therapeutic threshold of 5.97 ng/mL, 20% (95% CI: 8.1%-41.6%) had subtherapeutic endoxifen concentrations. CONCLUSIONS: A liquid chromatography-tandem mass spectrometry method was developed and fully validated according to the ICH M10 guidelines to simultaneously provide objective adherence measurements and TDM in a pilot study. This method enables clinicians to verify medication compliance and determine therapeutic concentrations by quantifying both tamoxifen adherence and endoxifen concentration in a single analysis.