کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1212077 | 1494049 | 2015 | 6 صفحه PDF | دانلود رایگان |
• A method was fully validated to determine nintedanib and BIBF 1202 in plasma.
• This is a sensitive analysis for nintedanib and its metabolite BIBF 1202.
• The plasma sample was prepared by a protein precipitation.
A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed to simultaneous determine nintedanib and BIBF 1202 in mice plasma and tissue using carbamazepine as the internal standard (IS). Sample preparation was accomplished through a protein precipitation procedure with acetonitrile. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with the mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution at a flow rate of 0.40 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 540.3 → 113.1 for nintedanib, m/z 526.3 → 113.1 for BIBF 1202 and m/z 237.1 → 194.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 1–1000 ng/mL with a lower limit of quantification of 1.0 ng/mL for each drug. Only 3.0 min was needed for an analytical run. The inter-day and intra-day precision and accuracy of quality control (QC) samples, evaluated both in plasma and tissue homogenates, were all within 15%. The method was successfully applied to the pharmacokinetic and tissue distribution study of nintedanib and BIBF 1202 in mice after oral administration of nintedanib.
Journal: Journal of Chromatography B - Volume 1002, 1 October 2015, Pages 239–244