PMID- 35774599
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic 
      Analysis of Voxtalisib in Rat Plasma.
PG  - 914733
LID - 10.3389/fphar.2022.914733 [doi]
LID - 914733
AB  - Voxtalisib, is a specific, effective, and reversible dual inhibitor, which 
      inhibits both pan-class I phosphoinositide 3-kinase (PI3K) and mechanistic target 
      of rapamycin (mTOR). To date, voxtalisib has been studied in trials for melanoma, 
      lymphoma, glioblastoma, breast cancer, and other cancers. In this study, a highly 
      sensitive and rapid ultra-performance liquid chromatography tandem mass 
      spectrometry (UPLC-MS/MS) technology was applied to the quantitative methodology 
      and pharmacokinetic analysis of voxtalisib in rat plasma. After protein 
      precipitation of the analyte by acetonitrile, the chromatographic separation was 
      performed by gradient elution on an Acquity BEH C18 column (2.1 mm x 50 mm, 
      1.7 mum) with acetonitrile (solvent A) and 0.1% formic acid (solvent B) as the 
      mobile phase. In the positive ion mode, the mass transfer detection of the 
      analyte and IS was m/z 270.91 > 242.98 and m/z 572.30 > 246.10, respectively. In 
      the concentration range of 1-2000 ng/ml, a good linear relationship of voxtalisib 
      was successfully established by the UPLC-MS/MS technology, and the lower limit of 
      quantification (LLOQ) of the analyte was identified as 1 ng/ml. Intra-day and 
      inter-day precisions for voxtalisib were 7.5-18.7% and 13.0-16.6%, respectively, 
      and the accuracies were in the ranges of -14.0-2.0% and -7.2-3.1%, respectively. 
      The matrix effect, extraction recovery, carryover and stability of the analyte 
      were all in compliance with the acceptance criteria of bioassays recommended by 
      FDA. Finally, the pharmacokinetic profile of the analyte had been availably 
      studied by the UPLC-MS/MS bio-analytical method after rats were treated by 
      intragastric administration with voxtalisib (5 mg/kg). The results indicated that 
      the UPLC-MS/MS technology can effectively and quickly quantify the analyte, and 
      this method can also be used for the pharmacokinetic study of voxtalisib, which 
      can provide reference for the optimization of clinical drug management in the 
      later period.
CI  - Copyright (c) 2022 Li, Liu, Wang, Hu, Hu, Xu, Shao and Chen.
FAU - Li, Qingqing
AU  - Li Q
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical 
      Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Liu, Ya-Nan
AU  - Liu YN
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical 
      Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Wang, Jing
AU  - Wang J
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical 
      Sciences, Wenzhou Medical University, Wenzhou, China.
FAU - Hu, Yingying
AU  - Hu Y
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Hu, Jinyu
AU  - Hu J
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Xu, Ren-Ai
AU  - Xu RA
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Shao, Liu
AU  - Shao L
AD  - Chongqing University Cancer Hospital, Chongqing, China.
FAU - Chen, Lianguo
AU  - Chen L
AD  - The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220614
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9237521
OTO - NOTNLM
OT  - UPLC-MS/MS technology
OT  - pharmacokinetic analysis
OT  - quantitative methodology
OT  - rat plasma
OT  - voxtalisib
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/02 06:00
MHDA- 2022/07/02 06:01
PMCR- 2022/06/14
CRDT- 2022/07/01 02:40
PHST- 2022/04/07 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/07/01 02:40 [entrez]
PHST- 2022/07/02 06:00 [pubmed]
PHST- 2022/07/02 06:01 [medline]
PHST- 2022/06/14 00:00 [pmc-release]
AID - 914733 [pii]
AID - 10.3389/fphar.2022.914733 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jun 14;13:914733. doi: 10.3389/fphar.2022.914733. 
      eCollection 2022.