A selective HPLC-MS/MS method for quantification of SND-117 in rat plasma and its application to a pharmacokinetic study

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 May 1:1052:60-65. doi: 10.1016/j.jchromb.2017.03.008. Epub 2017 Mar 12.

Abstract

Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder affects many adults. Sinomenine, a natural product, has been clinically available for the treatment of RA in China. SND-117, a sinomenine derivative with much more potent activity, might serve as a candidate for anti-arthritis. The aim of the present study was to develop a sensitive and rapid high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for quantification of SND-117 in rat plasma and to understand its absolute bioavailability. The HPLC-MS/MS method was developed and fully validated for determination of SND-117 in rat plasma, and the pharmacokinetic differences were investigated after different administration routes. The pharmacokinetics parameters were calculated by non-compartment model with DAS 3.0 software. After the oral or intravenous administration of different doses of SND-117, the time to peak is 1.5h, half-life time is 8-10h. The absolute oral bioavailability of SND-117 in rats was 9.60%. The results showed that SND-117 in rats was quickly absorbed, slowly eliminate, and the kinetics were linear. This method was suitable for pharmacokinetic studies of SNA-117 in rats.

Keywords: Anti-arthritis; HPLC–MS/MS; Pharmacokinetics; SND-117.

Publication types

  • Validation Study

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Animals
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / chemistry
  • Area Under Curve
  • Arthritis, Rheumatoid / drug therapy
  • Chromatography, High Pressure Liquid / methods*
  • Limit of Detection
  • Morphinans / administration & dosage
  • Morphinans / blood*
  • Morphinans / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • Antirheumatic Agents
  • Morphinans
  • sinomenine