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: Xia Ye, Minghai Tang, Juan Liu, Xianhuo Wang, Liang Ma, Hao Zheng, Jia Hu, Xiang Chen, Xingmei Duan, Lijuan Chen
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 56 Issue 2 Pg. 366-72 (Sep 10 2011) ISSN: 1873-264X [Electronic] England
• PMID: 21680128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• 5-(4-methoxybenzylidene)thiazolidine-2,4-dione
• Anti-Inflammatory Agents
• Thiazolidinediones
• Water
• Rosiglitazone
• Methanol

Topics

• Administration, Oral
• Animals
• Anti-Inflammatory Agents (administration & dosage, blood, pharmacokinetics)
• Calibration
• Chromatography, Liquid (standards)
• Dogs
• Drug Stability
• Guideline Adherence
• Guidelines as Topic
• Methanol (chemistry)
• Models, Biological
• Reference Standards
• Reproducibility of Results
• Rosiglitazone
• Sensitivity and Specificity
• Solid Phase Extraction
• Tandem Mass Spectrometry (standards)
• Thiazolidinediones (administration & dosage, blood, pharmacokinetics)
• Water (chemistry)