A Simple HPLC Method for the Determination of Ibrutinib in Rabbit

Latin American Journal of Pharmacy
(formerly Acta Farmacéutica Bonaerense)
Lat. Am. J. Pharm. 35 (1): 130-34 (2016)
Regular article
Received: August 16, 2015
Revised version: September 15, 2015
Accepted: September 16, 2015
A Simple HPLC Method for the Determination of Ibrutinib in Rabbit
Plasma and its Application to a Pharmacokinetic Study
Li-min WEI 1 *, Zhen-xing XU 2, Peng-fei LV 2,
Yong-le XUE 2, Xiang-xiang WANG 2, & Min ZHANG 2
1
The First Affiliated Hospital of Henan University of Science and Technology, 471003 Luoyang, PR China
2 Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China
SUMMARY. In this study, a simple, rapid and sensitive high performance liquid chromatography (HPLC)
method is developed for the determination of ibrutinib in rabbit plasma samples using vortioxetine as the
internal standard (IS). Sample preparation was accomplished through one-step liquid-liquid extraction
with ethyl acetate, and chromatographic separation was carried out on an Agilent ZORBAX SB-C18 (4.6
× 125 mm, 5 μm) at 35 °C. Mobile phase composed of a mixture of acetonitrile-0.1% trifluoroacetic acidwater (43:27:30) at a flow rate of 1.0 mL/min. Wavelength was set at 258 nm. The chromatographic retention times of ibrutinib and IS were 5.07 and 6.06 min, respectively. The lower limit of quantitation
(LLOQ) was 5.0 ng/mL, and no interferences were detected in the chromatograms. The devised HPLC
method was validated by evaluating its intra- and inter-day precisions and accuracies in a linear concentration range between 5.0 and 500 ng/mL. The method has also been successfully applied to a pharmacokinetic study of ibrutinib in rabbits for the first time, which provides the basis for the further development
and application of ibrutinib.
RESUMEN. En este estudio se ha desarrollado un método de cromatografía líquida de alto rendimiento (HPLC)
simple, rápido y sensible para la determinación de ibrutinib en muestras de plasma de conejo utilizando vortioxetina como patrón interno (IS). La preparación de la muestra se llevó a cabo a través de extracción líquido-líquido
de un solo paso con acetato de etilo, y la separación cromatográfica se desarrolló en una columna Agilent ZORBAX SB-C18 (4,6 × 125 mm, 5 μm) a 35 °C. La fase móvil estaba compuesta de una mezcla de agua-acetonitrilo-ácido trifluoroacético al 0,1% (43:27:30) a un caudal de 1,0 mL/min. La longitud de onda se fijó en 258 nm.
Los tiempos de retención de ibrutinib e IS fueron 5,07 y 6,06 min, respectivamente. El límite inferior de cuantificación (LLOQ) fue de 5,0 ng/mL y no se detectaron interferencias en los cromatogramas. El método de HPLC
ideado fue validado por la evaluación de sus precisiones y exactitudes intra- e inter-día en un intervalo de concentración lineal entre 5,0 y 500 ng/mL. El método se ha aplicado con éxito a un estudio farmacocinético de ibrutinib en conejos, por primera vez, lo que proporciona la base para el futuro desarrollo y aplicación del ibrutinib.
KEY WORDS: HPLC, ibrutinib, pharmacokinetics, plasma, rabbit.
*
130
Author to whom correspondence should be addressed. E-mail: [email protected]
ISSN 0326 2383 (printed ed.)
ISSN 2362-3853 (on line ed.)