Bora Kim, JunHwa Shim, SeungHwan Lee, Kyung-Sang Yu, Seo Hyun Yoon and Joo-Youn Cho
This study aimed to develop a highly sensitive, rapid method to evaluate the pharmacokinetic bioequivalence of two formulations of the anticancer drug, bicalutamide. According to US and Korean regulatory requirements for a bioequivalence test, we developed an achiral, bioanalytical method to determine bicalutamide levels in human plasma. The method included liquid chromatography tandem mass spectrometry in negative mode and was validated with nilutamide as an internal standard. Quantitation was performed for the transition of 429.2 → 255.0 (m/z) for bicalutamide and 316.2 → 273.2 (m/z) for nilutamide. The lower limit of quantitation was 10 ng mL‑1 with a 50 μL plasma sample. This sensitivity was about 8 times higher than current methods in pharmaceuticals and 10 times higher than methods for human plasma samples. The concentrations of seven working standards showed linearity between 10 and 2000 ng mL-1 (r2 ≥ 0.9993). Chromatographic separation was achieved within 4 min, compared to the 10 min of current methods. We used a Luna C18 column (100 mm x 2 mm, 5 μm) with distilled water/acetonitrile (30/70, v/v) as an isocratic mobile phase with a flow rate of 0.3 mL min-1. The average extraction recoveries of 3 quality control concentrations were 94.43% for bicalutamide and 99.28% for nilutamide. The coefficient of variation was ≤15% for intra- and inter-batch assays. Thus, this method satisfied the US and Korean validation requirements. When applied to a pharmacokinetic bioequivalence study in 33 healthy Korean male volunteers, this method showed high sensitivity, selectivity, and accuracy.
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