Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jchromb.2017.07.023
Title: Investigation of the effect of plasma albumin levels on regorafenib-induced hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry method
Authors: Pang, YY 
Tan, YL 
Ho, HK 
Keywords: LC–MS/MS
Plasma protein binding
Regorafenib
Chromatography, Liquid
Drug Stability
Humans
Limit of Detection
Linear Models
Phenylurea Compounds
Pyridines
Reproducibility of Results
Serum Albumin
Tandem Mass Spectrometry
Issue Date: 1-Sep-2017
Publisher: Elsevier BV
Citation: Pang, YY, Tan, YL, Ho, HK (2017-09-01). Investigation of the effect of plasma albumin levels on regorafenib-induced hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry method. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 1061-1062 : 220-224. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jchromb.2017.07.023
Abstract: Regorafenib is an oral multikinase inhibitor indicated for metastatic colorectal cancer and gastrointestinal stromal tumour. Due to its extensive plasma protein binding and low calculated hepatic extraction ratio, the hepatotoxicity observed with usage of the drug may be related to its plasma exposure. To investigate the highly dynamic free:bound drug concentration for regorafenib in the plasma, a bioanalytical liquid chromatography-tandem mass spectrometric assay was developed and validated in human plasma. The concentration range of the assay was 2–1000 ng/mL. Sample preparation was via protein precipitation using acetonitrile with sorafenib as the internal standard. The supernatant was injected into an ultra-performance liquid chromatographic system coupled to a triple quadrupole mass spectrometer. The analytes were separated on an AQUITY UPLC BEH C18 column (120 Å, 1.7 μm, 2.1 mm × 50 mm) and eluted with a gradient elution system. The ions were detected in multiple reaction monitoring mode. The linearity, lower limit of quantification, intra-day and inter-day precision and accuracy conformed to FDA guidelines. The validated method was successfully applied to determine the effect of albumin levels in plasma on the extent of protein binding of regorafenib. The results indicated that physiologically-relevant levels of albumin were found to have no significant effect on the extent of protein binding of regorafenib, hence imposing minimal effect on drug disposition.
Source Title: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/226976
ISSN: 15700232
1873376X
DOI: 10.1016/j.jchromb.2017.07.023
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Investigation of the effect of plasma albumin levels on regorafenib-induced hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry method..pdfPublished version280.75 kBAdobe PDF

CLOSED

None

SCOPUSTM   
Citations

4
checked on Sep 23, 2022

Page view(s)

31
checked on Sep 22, 2022

Download(s)

3
checked on Sep 22, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.