Browsing by Author "Govender, Justine Tia"

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    Assessing Non-adherence in South African Women on Tamoxifen Treatment for Breast Cancer
    (Stellenbosch : Stellenbosch University, 2024-12) Govender, Justine Tia; Kellerman, Tracy Ann; Decloedt, Eric Hermann; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine.
    Introduction: Adherence to tamoxifen is a major challenge in patients with hormone receptor-positive breast cancer. Endoxifen, tamoxifen’s main active metabolite, measured along with the parent drug, can be used as an adherence tool. A pilot study was undertaken to assess adherence in South African women by quantification of tamoxifen and endoxifen in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: The study recruited 20 oestrogen receptor-positive female breast cancer patients on tamoxifen. An adherence questionnaire was administered, clinical information collected, and plasma samples obtained for concentration measurement. A Shimadzu LCMS-8040 instrument was used to develop and validate a method to quantify tamoxifen and endoxifen in plasma. The transitions of tamoxifen and endoxifen: m/z 372 → 129; 91.1; 128 and m/z 374 → 223; 129; 152, respectively, were monitored in the positive ion mode. The LC-MS/MS method utilises an Agilent Poroshell 120 EC-C18 column and mobile phases of 0.1% formic acid in water (A) and acetonitrile (B) at a flow rate of 0.600 mL/min, together with a protein precipitation (PP) extraction method. Results and Discussion: Participant ages ranged from 32-73 years. Most participants (60%) had stage 4 breast cancer, with others distributed across earlier stages. Tamoxifen was prescribed primarily as palliative treatment (60%), followed by curative (35%) and prophylactic (5%) uses. The sample consisted mostly of preand post-menopausal women (45% each). Regarding comorbidities, 45% had none, 40% had one, and 15% had two. Only 2/20 participants were HIV positive. Tamoxifen and endoxifen plasma concentrations ranged from 11.7-340 ng/mL and 3.64-34.2 ng/mL, respectively. Objective non-adherence was low (5%), while subjective non-adherence was higher (45%). This resulted in failure to reject the null hypothesis of weak agreement between subjective and objective adherence measures. The LC-MS/MS method had quadratic regression weighted calibration curves (1/c) with concentration ranges of 4.69-600 ng/mL and 1.56-200 ng/mL for tamoxifen and endoxifen, respectively. Both analytes were stable under various storage conditions. No matrix effects were observed, and haemolysis at 2.0% did not affect analyte quantification. Average recovery was 89.6% for tamoxifen and 96.8% for endoxifen, with process efficiencies of 92.8% and 75.7%, respectively. Intra- and inter-validations met EMA (2011), FDA (2018) and ICH (2022) guidelines. Calibration standard (STD) % accuracies ranged from 97.6-101.7% for tamoxifen and 97.1-104.5% for endoxifen. Quality control (QC) % accuracies ranged from 104.5-113.2% for tamoxifen and 105.3-110.0% for endoxifen. Both analytes were stable in plasma through three freeze/thaw cycles and on bench for 6 h. Autosampler and re-injection stability was demonstrated at 8.00°C for 24 h. Conclusion: An LC-MS/MS method was successfully validated and applied to a clinical study to assess adherence in South African breast cancer patients. Poor agreement between subjective and objective adherence measures was demonstrated, emphasising the importance of direct measures in adherence assessment. The study highlighted the need to consider the measurement of tamoxifen and endoxifen concentrations to assess adherence and to optimise tamoxifen treatment.