Quantitation of tazemetostat in human plasma using liquid chromatography-tandem mass spectrometry.
LC–MS/MS
human plasma
pharmacokinetics
tazemetostat
validation
Journal
Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241
Informations de publication
Date de publication:
23 May 2024
23 May 2024
Historique:
revised:
06
05
2024
received:
26
02
2024
accepted:
08
05
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
24
5
2024
Statut:
aheadofprint
Résumé
To support a phase 1 trial in patients with lymphomas, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for tazemetostat quantitation in 20 μL of human plasma. After protein precipitation, chromatographic separation employed a Kinetex C18 column and a gradient of 0.1% formic acid in both water and acetonitrile, during a 3-min run time. Detection was achieved using a SCIEX 6500+ tandem mass spectrometer with electrospray positive-mode ionization. Validation was based on the latest Food and Drug Administration guidance. With a stable isotopic internal standard, the assay was linear within the range of 10-5000 ng/mL and proved to be accurate (91.9%-103.7%) and precise (<4.4% imprecision). Recovery varied between 93.3% and 121.1%, and matrix effect ranged from -25.5% to -4.9%. Hemolysis, lipemia, and dilution did not impact quantitation. Plasma stability was confirmed after three freeze-thaw cycles, 24 h at room temperature, and 4 months at -80°C. Incurred sample reanalysis yielded 94.4% samples within 20% difference (n = 36). External validation showed a mean bias of -11.1%. Pharmacokinetic (PK) data obtained from three patients suggested variable concentration time profiles, warranting collection of further data. The assay proved to be suitable for tazemetostat quantitation in human plasma and will support clinical studies by defining tazemetostat PKs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e5903Subventions
Organisme : Fundamental Research Funds for the Central Universities, Southwest Minzu University
ID : P30CA47904
Organisme : Fundamental Research Funds for the Central Universities, Southwest Minzu University
ID : R50CA211241
Organisme : Fundamental Research Funds for the Central Universities, Southwest Minzu University
ID : U24CA247643
Organisme : Fundamental Research Funds for the Central Universities, Southwest Minzu University
ID : UM1CA186690
Organisme : NCI NIH HHS
ID : UM1 CA186690
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA247643
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211241
Pays : United States
Organisme : UPMC Hillman Cancer Center's Cancer Pharmacokinetics
Organisme : Pharmacodynamics Facility (CPPF)
ID : P30 CA47904
Informations de copyright
© 2024 John Wiley & Sons Ltd.
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