Development and validation of a sensitive LC–MS/MS method for the assay of four PARP inhibitors in human plasma and its application in ovarian cancer patients
PARP inhibitors have demonstrated marked efficacy in ovarian cancer patients with BRCA1/2 loss-of-function mutations. In this study, we established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method to simultaneously quantify the four frequently prescripted PARP inhibitors, namely niraparib, olaparib，fluzoparib, and pamiparib, in ovarian cancer. The mobile phase was 50 % methanol with 0.1 % formic acid at a flow rate of 0.3 mL/min, within 8 min run time. Four PARP inhibitors were separated on a Hypersil GOLD™ aQ C18 Polar Endcapped LC column (50 × 2.1 mm, 1.9 µm) at 35 ℃ and subjected to mass analysis using positive electro-spray ionization (ESI). The linear range of this method was 10-2000 ng/mL, 25-5000 ng/mL, and 50-10,000 ng/mL for niraparib, olaparib and fluzoparib, and pamiparib, respectively, with the correlation coefficients (r