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A rapid and sensitive method for quantification of ibrutinib in rat plasma by UPLC–ESI–MS/MS: validation and application to pharmacokinetic studies of a novel ibrutinib nanocrystalline
Authors:Shuangshuang Sun  Dongfang Cheng  Shumeng Kong  Xiangping Li  Tongfang Li  Qinglong Yu  Lin Wang
Institution:Yantai Key Laboratory of Nanomedicine and Advanced Preparations, Yantai Institute of Materia Medica, Yantai, China
Abstract:Ibrutinib has an excellent effect in the treatment of mantle cell lymphoma so it has attracted much attention. A novel ibrutinib nanocrystalline was exploited in our study to improve the bioavailability. A fast and reliable UPLC–MS/MS method was established for the accurate quantification of ibrutinib in rat plasma. The chromatographic separation was achieved by an Agilent zorbax SB-C18 rapid solution HD column (2.1 × 50 mm, 1.8 μm). The mobile phase consisted of deionized water (containing 10 mm ammonium acetate and 0.1% formic acid) and pure acetonitrile. Isocratic elution (water–acetonitrile 10:90, v/v) was adopted and the flow rate was 0.4 mL/min. Column temperature was set to 40°C. Vilazodone was used as the internal standard in this analytical method. Multiple reaction monitoring mode with positive electrospray ionization was selected to detect ibrutinib and vilazodone. Acetonitrile was used to precipitate protein to extract plasma samples. There was no endogenous interference for both ibrutinib and vilazodone and the linear range of this method was 1–2000 ng/mL. The recoveries were 98.4, 97.4 and 102.7% at low, medium and high concentrations. Accordingly, the matrix effect was 96.6, 111.1 and 99.6%. The pharmacokinetic difference between ibrutinib crude and a novel ibrutinib nanocrystalline in rats was investigated by this validated method successfully. The peak concentration and area under the concentration–time curve showed significant differences in gender and the bioavailability was improved after oral administration of ibrutinib nanocrystalline.
Keywords:bioavailability  ibrutinib  nanocrystalline  pharmacokinetics  UPLC–MS/MS
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