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 |
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Erscheinungsjahr: |
2024 2023 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:237 |
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Enthalten in: |
Journal of pharmaceutical and biomedical analysis - 237(2023) vom: 05. Jan., Seite 115758 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wei, Yuru [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 03.11.2023 Date Revised 03.11.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.jpba.2023.115758 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM363254404 |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
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700 | 1 | |a Wang, Xueding |e verfasserin |4 aut | |
700 | 1 | |a Lan, Chunyan |e verfasserin |4 aut | |
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