Quantitation of Niraparib in Human Plasma by LC‐MS/MS

Polyadenosine diphosphate–ribose polymerase 1 (PARP‐1) and 2 (PARP‐2) are key DNA repair enzymes that promote single‐strand break repair via the base excision pathway. Niraparib, a PARP inhibitor, has shown clinical efficacy with the reduction of disease progression or death and progression‐free survival benefit across multiple clinical trials, leading to the Food and Drug Administration (FDA) approval for the treatment of advanced and recurrent ovarian cancers. This study presents a robust and simple 5‐min assay designed for the quantitation of the single agent niraparib in human plasma utilizing liquid chromatography–tandem mass spectrometry (LC‐MS/MS). A 50 μL volume of plasma was subjected to protein precipitation, followed by chromatographic separation using a Phenomenex Kinetex C18 column (2.6 μm, 50 × 2.1 mm) and a gradient mobile phase system consisting of 0.1% formic acid in both water and acetonitrile during a 5‐min run time. Mass spectrometric detection was achieved using a SCIEX 6500 + tandem mass spectrometer with electrospray positive‐mode ionization. With a stable isotopic internal standard, our assay met the criteria outlined by the FDA guidance for bioanalytical method validation, demonstrating robust performance within the range from 5 to 5000 ng/mL. This assay will support future clinical studies by defining niraparib pharmacokinetics.