title: Development and validation of a UPLC-MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs.
abstract: SKLB010 is currently under development as a potential therapeutic agent for the treatment of acute hepatitis and rheumatoid arthritis. The purpose of this paper was to investigate the pre-clinical pharmacokinetics of SKLB010 in beagle dogs. An ultra performance liquid chromatographic tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the quantitative determination of SKLB010 in dog plasma, using rosiglitazone as the internal standard (I.S.). Plasma samples were prepared by a simple solid phase extraction (SPE) method. The analyte and internal standard were separated by an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with a mobile phase of methanol-water (80/20, v/v) over 2 min. Detection was based on the multiple reaction monitoring with the precursor-to-product ion transitions m/z 234.10→147.92 (SKLB010) and m/z 356.15→150.00 (I.S.). The method was validated according to FDA guidelines on bio-analytical method validation. The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression and stability were within the acceptable ranges. The method described above was successfully applied to reveal the single- and multi-pharmacokinetic profiles of SKLB010 in beagle dogs and should be extendable to pharmacokinetic studies in other species as well.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ye
authors.forename: Minghai
authors.initials: M
authors.lastname: Tang
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Xianhuo
authors.initials: X
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Xingmei
authors.initials: X
authors.lastname: Duan
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D004285:Dogs; D004355:Drug Stability; D019983:Guideline Adherence; D017408:Guidelines as Topic; D000432:Methanol / Q000737:chemistry; D008954:Models, Biological; D012015:Reference Standards; D015203:Reproducibility of Results; D000077154:Rosiglitazone; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000592:standards; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
chemical_list: C546799:5-(4-methoxybenzylidene)thiazolidine-2,4-dione; D000893:Anti-Inflammatory Agents; D045162:Thiazolidinediones; D014867:Water; D000077154:Rosiglitazone; D000432:Methanol