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.