Abstract：
:A sensitive, selective and rapid liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantification of the novel transforming growth factor-β (TGF-β) inhibitor SB-505124 in rat plasma and then validated. Plasma samples were prepared by simple protein precipitation. Separation was performed on a Diamonsil ODS chromatography column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. SB-505124 and the internal standard doxorubicin were detected in the positive ion mode using multiple reaction monitoring of the transitions at m/z 336.2→320.1 and 544.2→397.2, respectively. Calibration curve was linear (r>0.9996) over a concentration range of 10-5000 ng/mL with the lower quantification limit of 10 ng/mL. Both intra- and inter-day precision were within 6.5% and trueness were not more than 3.1%. Extraction recovery and matrix effect were within acceptable limits. Stability tests showed that SB-505124 and the IS remained stable throughout the analytical procedure. The validated LC-MS/MS method was then used to analyze the pharmacokinetics of SB-505124 administered to rats intravenously (8 mg/kg) or orally (10 mg/kg). Oral bioavailability of SB-505124 was calculated as 76.4%, indicating the potential of SB-505124 as an orally administered drug.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Jiang J,Zhang Y,Zhang Q,Li Y,Gong T,Zhang Z,Ding R,Sun Xdoi
10.1016/j.jpba.2015.09.002subject
Has Abstractpub_date
2016-01-05 00:00:00pages
205-9eissn
0731-7085issn
1873-264Xpii
S0731-7085(15)30143-6journal_volume
117pub_type
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