Preclinical Pharmacokinetics Evaluation of Anti-heparin-binding EGF-like Growth Factor (HB-EGF) Monoclonal Antibody Using Cynomolgus Monkeys via 89Zr-immuno-PET Study and the Determination of Drug Concentrations in Serum and Cerebrospinal Fluid

2015 ◽  
Vol 33 (2) ◽  
pp. 476-486 ◽  
Author(s):  
Noriyuki Kasai ◽  
Maiko Adachi ◽  
Kazuya Yamano
Keyword(s):  
Monoclonal Antibody ◽  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Heparin Binding ◽  
Cynomolgus Monkeys ◽  
Preclinical Pharmacokinetics ◽  
Drug Concentrations

scholarly journals Expression of the Heparin-Binding Growth Factor Midkine in the Cerebrospinal Fluid of Patients with Neurological Disorders

2008 ◽  
Vol 47 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Yoshihiro Yoshida ◽  
Shinya Ikematsu ◽  
Hisako Muramatsu ◽  
Harutoshi Sakakima ◽  
Nobuhisa Mizuma ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Neurological Disorders ◽  
Heparin Binding

scholarly journals Effect of antigen-dependent clearance on pharmacokinetics of anti-heparin-binding EGF-like growth factor (HB-EGF) monoclonal antibody

mAbs ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 1220-1228 ◽  
Author(s):  
Noriyuki Kasai ◽  
Yukitaka Yoshikawa ◽  
Junichi Enokizono
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Heparin Binding

DDRE-12. DETERMINATION OF TOTAL AND UNBOUND LEVELS OF A POTENT INHIBITOR OF FIBROBLAST GROWTH FACTOR RECEPTOR, INFIGRATINIB, IN HUMAN PLASMA, CEREBROSPINAL FLUID AND BRAIN TUMOR BY A VALIDATED LC-MS/MS ASSAY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi76-vi77
Author(s):  
Tigran Margaryan ◽  
Nader Sanai ◽  
Artak Tovmasyan
Keyword(s):  
Clinical Trial ◽  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Human Plasma ◽  
Fibroblast Growth Factor Receptor ◽  
Potent Inhibitor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Phase 0

Abstract BACKGROUND Infigratinib is an orally available potent inhibitor of fibroblast growth factor receptor (FGFR) under investigation in a Phase 0 clinical trial for recurrent high-grade gliomas harboring oncogenic FGFR mutation or translocation (NCT04424966). Here, we report on our development and validation of an LC-MS/MS method for determination of total and unbound levels of infigratinib in human plasma, cerebrospinal fluid (CSF) and glioblastoma tissue. METHODS Infigratinib was extracted from human plasma, CSF and glioblastoma homogenate samples by protein precipitation with methanol. Unbound fractions of infigratinib in plasma and brain tissues were determined by equilibrium dialysis. Validation was performed using Sciex ExionLC UHPLC system coupled with Sciex QTRAP 6500+ MS/MS detector using positive electrospray ionization mode. The method was validated according to FDA guidelines and CAP/CLIA regulations. RESULTS The method was validated for 0.2-1000 nmol/L concentration range using plasma as matrix for all biospecimens. The analytical separation was optimized on Phenomenex Kinetex™ F5 column with total run time of 3.5 min using isocratic mode. Maximum coefficient of variation for intra- and inter-day precision was 12.7% and the accuracy was within 88.5-115.0% in all matrixes. The analyte is stable in plasma for at least 19 hours at room temperature (RT). Plasma stability at -20°C was demonstrated for at least 119 days. Stability of stock and working solutions was demonstrated for at least 15 hours (RT) and 60 days (2-8°C). The unbound fraction of infigratinib in pooled human plasma and brain were determined to be 0.01. CONCLUSIONS A sensitive and rapid bioanalytical method is successfully developed and validated to quantify total and unbound infigratinib levels in human plasma, CSF and glioblastoma tissue. The method is presently employed to evaluate plasma pharmacokinetics and CNS penetration of infigratinib in recurrent glioblastoma patients in an ongoing Phase 0 clinical trial.

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