title: Development and validation of an LC-MS/MS method for the determination of SB-505124 in rat plasma: Application to pharmacokinetic study.
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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Yuandong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Institute for Drug Control, Beijing 100035, PR China. Electronic address: dingrui1001@aliyun.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin Road, Chengdu, Sichuan 610041, PR China. Electronic address: sxcelia22@163.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D007093:Imidazoles; D011725:Pyridines; D018125:Receptors, Transforming Growth Factor beta
keywords: LC–MS/MS; Pharmacokinetic study; Rat plasma; SB-505124; Validation