title: Determination of HS270, a new histone deacetylase inhibitor, in rat plasma by LC-MS/MS--application to a preclinical pharmacokinetic study.
abstract: A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and fully validated to determine HS270, a new histone deacetylase (HDAC) inhibitor, in rat plasma using SAHA as the internal standard (IS). After a single step liquid-liquid extraction with acetoacetate, analytes were subjected to LC-MS/MS analysis using positive electro-spray ionization (ESI(+)) under selected reaction monitoring mode (SRM). The chromatographic separation was achieved on a Hypurity C(18) column (50 mm × 2.1 mm, i.d., 5 μm). The MS/MS detection was conducted by monitoring the fragmentation of m/z 392.3→100.1 for HS270, m/z 265.1→232.1 for IS. The method had a chromatographic running time of 2.5 min and linear calibration curves over the concentrations of 0.5-1000 ng/mL. The recovery of the method was 70.8-82.5% and the lower limit of quantiﬁcation (LLOQ) was 0.5 ng/mL. The intra- and inter-batch precisions were less than 15% for all quality control samples at concentrations of 1.0, 100.0, and 750.0 ng/mL. The validated LC-MS/MS method has successfully applied to a HS270 pharmacokinetic study after oral doses of 25, 50, 100, 200 mg/kg, and i.v. dose of 5 mg/kg to rats.
authors: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors: Guo-Ping
authors: GP
authors: Zhong
authors: Jiang-Ying
authors: JY
authors: Chen
authors: Hui-Chang
authors: HC
authors: Bi
authors: Xiao-Ling
authors: XL
authors: Qin
authors: Chang-Liang
authors: CL
authors: Dai
authors: Jing
authors: J
authors: Liu
authors: Xiao
authors: X
authors: Chen
authors: Gui-Xiong
authors: GX
authors: Zeng
authors: Zhi-Ying
authors: ZY
authors: Huang
authors: Min
authors: M
authors: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006877:Hydroxamic Acids / Q000032:analysis; D016014:Linear Models; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat