title: Determination of CUDC-101 in rat plasma by liquid chromatography mass spectrometry and its application to a pharmacokinetic study.
abstract: CUDC-101 is a multi-targeted, small-molecule inhibitor of histone deacetylase (HDAC), epidermal growth factor receptor tyrosine kinase (EGFR/ErbB1), and human epidermal growth factor receptor 2 tyrosine kinase (HER2/neu or ErbB2) with potential antineoplastic activity. A sensitive and selective liquid chromatography mass spectrometry method for determination of CUDC-101 in rat plasma was developed. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 μm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used for quantification using target fragment ions m/z 435 for CUDC-101 and m/z 237 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for CUDC-101 in rat plasma. Mean recoveries of CUDC-101 in rat plasma were in the range of 84.0-90.5%. RSD of intra-day and inter-day precision were both <14%. The method was successfully applied to pharmacokinetic study of CUDC-101 after intravenous administration of single dosage 5 mg/kg in rats.
authors.affiliation: Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Ma
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University, Wenzhou 325035, China. Electronic address: lankywang@foxmail.com.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: C549566:7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011799:Quinazolines
keywords: CUDC-101; HDAC; LC–MS; Pharmacokinetics; Rat plasma