Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-μL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-μg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25–10 μg/mL with a coefficient of determination (r2) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8–4.1% and 1.3–3.3%, respectively. The assay accuracy was −2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting.
Voriconazole is an antifungal drug used to treat invasive aspergillosis. Voriconazole exhibits nonlinear behavior and considerable individual variability in its pharmacokinetic profile. Invasive aspergillosis has a poor prognosis, and failure of treatment owing to low voriconazole blood levels is undesirable. Thus, therapeutic drug monitoring (TDM) of voriconazole is recommended. However, plasma voriconazole concentration is rarely measured in hospitals, and the TDM of voriconazole is not widely practiced in Japan. We aimed to develop an ultra-simple method to measure plasma voriconazole concentration. Ten microliters of plasma sample was extracted, and proteins were precipitated using methanol extraction. Voriconazole and ketoconazole (internal standard) were separated using high-performance liquid chromatography. A calibration curve was prepared, which was linear over plasma voriconazole concentrations of 0.125–12.5 µg/mL, with a coefficient of determination of 0.9999. The intra-day and inter-day validation coefficients were 0.9%–2.2% and 1.3%–6.1%, respectively. The assay accuracy was −4.2% to 1.6%, and recovery was > 97.8%. Our ultra-simple, sensitive, and inexpensive high-performance liquid chromatography ultraviolet method to determine plasma voriconazole concentration will help improve the voriconazole TDM implementation rate and contribute to effective and safe voriconazole use.
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