Development and Validation of an LC-MS/MS Method for AC1LPSZG and Pharmacokinetics Application in Rats.
Journal
Journal of chromatographic science
ISSN: 1945-239X
Titre abrégé: J Chromatogr Sci
Pays: United States
ID NLM: 0173225
Informations de publication
Date de publication:
01 Jan 2022
01 Jan 2022
Historique:
received:
01
07
2020
revised:
08
12
2020
accepted:
31
01
2021
pubmed:
6
3
2021
medline:
12
1
2022
entrez:
5
3
2021
Statut:
ppublish
Résumé
Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC-MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose-response for quantification was observed over the range of 10-5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87-102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at -80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.
Identifiants
pubmed: 33667297
pii: 6153993
doi: 10.1093/chromsci/bmab020
pmc: PMC8742608
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26-34Subventions
Organisme : NIMHD NIH HHS
ID : G12 MD007605
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007605
Pays : United States
Organisme : NIH HHS
ID : RCMI, G12MD007605
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Références
Am J Mod Chromatogr. 2014;1(1):1-11
pubmed: 25594071
F1000Res. 2019 Jul 2;8:
pubmed: 31316753
J Hematol Oncol. 2019 Jul 5;12(1):71
pubmed: 31277692
J Org Chem. 2014 Apr 4;79(7):3140-51
pubmed: 24617596
Sci Rep. 2018 Feb 5;8(1):2405
pubmed: 29402925
Curr Opin Cell Biol. 2011 Dec;23(6):744-55
pubmed: 21963299
Cancers (Basel). 2017 Nov 01;9(11):
pubmed: 29104248
Lung Cancer. 2011 Oct;74(1):25-9
pubmed: 21371773
Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35
pubmed: 21157483
J Hematol Oncol. 2009 Oct 27;2:45
pubmed: 19860903
Chem Rev. 2011 Oct 12;111(10):6022-63
pubmed: 21696217
Rapid Commun Mass Spectrom. 2005;19(15):2131-6
pubmed: 15988723
Biochem Pharmacol. 2014 Aug 1;90(3):197-207
pubmed: 24863259