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

Copyright © 2023. Published by Elsevier B.V..

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 (r2) ≥ 0.99. Accuracies ranged from 93.12 %-110.71 and the inter- and intra-batch precisions were less than 15 % for all analytes in quality control samples. There was no significant matrix effect. Twenty-eight plasma samples were obtained from Sun Yat-sen University Cancer Center. The mean plasma concentrations (±SD) of niraparib and olaparib were 424.76 (±228.35) ng/mL and 1760.47 (±1739.69) ng/mL, respectively. The validated LC-MS/MS method allows the convient and efficient determination of four PARP inhibitors' exposure levels in ovarian cancer patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

2023

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:237

Enthalten in:

Journal of pharmaceutical and biomedical analysis - 237(2023) vom: 05. Jan., Seite 115758

Sprache:

Englisch

Beteiligte Personen:

Wei, Yuru [VerfasserIn]
Liang, Haixi [VerfasserIn]
Liu, Shu [VerfasserIn]
Guan, Shaoxing [VerfasserIn]
Ma, Kaiyun [VerfasserIn]
Guan, Yanping [VerfasserIn]
Chen, Youhao [VerfasserIn]
Huang, Min [VerfasserIn]
Wang, Xueding [VerfasserIn]
Lan, Chunyan [VerfasserIn]

Links:

Volltext

Themen:

8375F9S90C
BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
BRCA2 protein, human
Fluzoparib
Journal Article
Niraparib
Olaparib
Pamiparib
Poly(ADP-ribose) Polymerase Inhibitors
Therapeutic drug monitoring
UPLC–MS/MS

Anmerkungen:

Date Completed 03.11.2023

Date Revised 03.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jpba.2023.115758

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM363254404