Simultaneous Determination of Celecoxib, Dezocine and Dexmedetomidine in Beagle Plasma Using UPLC-MS/MS Method and the Application in Pharmacokinetics

Drug Des Devel Ther. 2021 Jun 15:15:2529-2541. doi: 10.2147/DDDT.S314562. eCollection 2021.

Abstract

Background: An efficient, fast and sensitive ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for simultaneous determination of celecoxib (CEL), dezocine (DEZ) and dexmedetomidine (DEX) in beagle plasma were established.

Methods: The beagle dogs plasmawas precipitated by acetonitrile. The column was Acquity UPLC BEH C18 column and the mobile phase was acetonitrile-formic acid with gradient mode, and the flow rate was set at 0.4 mL/min. Under the positive ion mode, CEL, DEZ, DEX and Midazolam (internal standard, IS) were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 381.10→282.10 for CEL, m/z 246.20→147.00 for DEZ, m/z 201.10→94.90 for DEX, and m/z 326.10→291.10 for IS.

Results: This UPLC-MS/MS method had good linearity for CEL, DEZ and DEX. The RSDs of inter-day and intra-day precision were the values of 0.31-7.66% and 0.11-9.63%, respectively; the RE values were from -6.05% to 10.98%. The extraction recovery was more than 79%, and the matrix effect was around 100%. The RSDs of stability were less than 8.96%. All of them met the acceptance standard of biological analysis method recommended by FDA.

Conclusion: This UPLC-MS/MS method is an effective tool for the simultaneous determination of CEL, DEX and DEX, and has been successfully applied to the study of pharmacokinetics in beagle dogs.

Keywords: UPLC-MS/MS; beagles; celecoxib; dexmedetomidine; dezocine; pharmacokinetics.

Publication types

  • Validation Study

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacokinetics
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics*
  • Celecoxib / administration & dosage
  • Celecoxib / pharmacokinetics*
  • Chromatography, High Pressure Liquid / methods*
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacokinetics*
  • Dogs
  • Drug Therapy, Combination
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacokinetics*

Substances

  • Analgesics
  • Bridged Bicyclo Compounds, Heterocyclic
  • Tetrahydronaphthalenes
  • Dexmedetomidine
  • Celecoxib
  • dezocine