Title :

Development and validation of an UHPLC-MS/MS method for simultaneous quantification of ibrutinib and its dihydrodiol-metabolite in human cerebrospinal fluid.

Author(s) :

Beauvais, D [Auteur]
Goossens, J-F [Auteur]
Boyle, Eileen [Auteur]
Allal, B [Auteur]
Lafont, T [Auteur]
Chatelut, E [Auteur]
Herbaux, Charles [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
GENAY, Stéphanie [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Odou, Pascal [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Danel, Cecile [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]

Journal title :

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

Abbreviated title :

J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.

Volume number :

1093-1094

Pages :

158-166

Publication date :

2018-09-01

ISSN :

1873-376X

Keyword(s) :

Adenine
Chromatography
High Pressure Liquid
Humans
Limit of Detection
Lymphoma
B-Cell
Pyrazoles
Pyrimidines
Reproducibility of Results
Tandem Mass Spectrometry
B-cell malignancies
Cerebrospinal fluid
Dihydrodiol-ibrutinib
Ibrutinib
LC-MS/MS

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Ibrutinib is an orally administered first-in-class irreversible Bruton's tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies. Several isolated clinical observations reported its ...
Show more >Ibrutinib is an orally administered first-in-class irreversible Bruton's tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies. Several isolated clinical observations reported its efficacy in central nervous system dissemination. Herein, we described the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedure for the quantification of ibrutinib and its active metabolite PCI-45227 in cerebrospinal fluid (CSF). This is the first complete validated method for quantification of ibrutinib and PCI-45227 in CSF. The compounds were eluted on a Waters BEH C18 column (50.0 × 2.1 mm; 1.7 μm) using a gradient elution with a mobile phase composed of ammonium formate buffer 5 mM pH 3.2 and acetonitrile +0.1% formic acid with a flow rate of 400 μL·min-1. Two deuterated internal standards were used to obtain the most accurate quantification. The CSF samples were prepared by a simple and rapid dilution. The method was validated by testing the selectivity, response function, intra-day and inter-day precisions, trueness, limits of detection (LOD) and lower limits of quantification (LLOQ). The validation results proved that the methods were suitable to quantify ibrutinib and PCI-45227 in real biological CSF samples from 0.50 (ibrutinib) or 1.00 (PCI-45227) to 30.00 ng·mL-1. Furthermore, the developed method was adapted to allow the quantification of both compounds in plasma and the results were compared to those reported in literature. The plasmatic samples were treated by protein precipitation and the method was validated to quantify ibrutinib and PCI-45227 in real biological plasmatic samples from 5.00 to 491 ng·mL-1. Lastly, for both matrices, accuracy profiles were plotted from the trueness and precision results using a 20% α-risk (β = 80%) and the tolerance intervals were comprised within the acceptance limits fixed at ±25% for the LLOQ and ±15% for the other concentrations. Finally, these methods were successfully applied to quantify ibrutinib and PCI-45227 in real human CSF and plasma samples.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Research team(s) :

Innovation/évaluation des médicaments injectables
Modélisation biopharmaceutique et pharmacocinétique
Innovation/évaluation des dispositifs médicaux de perfusion

Submission date :

2019-02-26T17:06:54Z