A simple and highly sensitive high-performance liquid chromatography (HPLC) method was developed for the quantification of ponatinib in human plasma. The developed HPLC method was validated based on International D.S. Food and Drug Administration guidelines. This technique utilized a solid-phase extraction step and required only 200μL plasma for a single analysis. The lower limit of quantification for ponatinib was 1.0ng/mL. Coefficients of variation and accuracies for intra- and interday assays were less than 10.8% and within 13.7%, respectively. The precision and accuracy of our HPLC assay was suitable for pharmacokinetic studies of ponatinib. On day 8 after beginning ponatinib therapy with an initial dose of 15mg, patients having a ponatinib C0 of less than 23ng/mL by HPLC may require a dose adjustment to 30mg to obtain a C0 of 23ng/mL of more. The median ponatinib C0 in 6 Japanese patients taking a 15mg daily dose was 24.6ng/mL, which was greater than the target concentration of 23ng/mL, and that of patients taking 30mg increased to a plasma concentration of 48.0ng/mL. This novel treatment strategy using the HPLC method developed herein may be useful for routine ponatinib therapy.
Keywords: Dose escalation; High-performance liquid chromatography; Human plasma; Ponatinib.
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