Olaparib (AZD2281) is an orally active PARP-1 inhibitor, primarily effective\nagainst cancers with BRCA1/2 mutations. It is currently in Phase III development and\nhas previously been investigated in numerous clinical trials, both as a single agent and in\ncombination with chemotherapy. Despite this widespread testing, there is only one published\nmethod that provides assay details and stability studies for olaparib alone. A more sensitive\nuHPLC-MS/MS method for the quantification of olaparib in human plasma was developed,\nincreasing the range of quantification at both ends (0.5ââ?¬â??50,000 ng/mL) compared to previously\npublished methods (10ââ?¬â??5,000 ng/mL). The wider range encompasses CMAX levels produced\nby typical olaparib doses and permits better pharmacokinetic modeling of olaparib\nelimination. This assay also utilizes a shorter analytical runtime, allowing for more rapid\nquantification and reduced use of reagents. A liquid-liquid extraction was followed by\nchromatographic separation on a Waters UPLCÃ?® BEH C18 column (2.1 Ã?â?? 50 mm, 1.7 ?m)\nand mass spectrometric detection. The mass transitions m/z 435.4281.1 and m/z\n443.2281.1 were used for olaparib and the internal standard [2H8]-olaparib, respectively.\nThe assay proved to be accurate (<9% deviation) and precise (CV < 11%). Stability studies showed that olaparib is stable at room temperature for 24 h. in whole blood, at 4 Ã?°C for\n24 h post-extraction, at 80 Ã?°C in plasma for at least 19 months, and through three\nfreeze-thaw cycles. This method proved to be robust for measuring olaparib levels in\nclinical samples from a Phase I trial.
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