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

• Published in: Drug design, development and therapy development and therapy, 2021-01, Vol.15, p.2529-2541
• Main Authors: Hu, Jie, Su, Xin-Juan, Si, Hui-Ling, Song, Rui-Xiang, Zhang, Fang, Qiu, Xiang-Jun, Chen, Xing-Peng
• Format: Article
• Language: English
• Subjects: Acetonitrile; Analgesics; Analgesics - administration & dosage; Analgesics - pharmacokinetics; Anesthesia; Angiogenesis inhibitors; Animals; beagles; Biological analysis; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics; Calibration; Celecoxib; Celecoxib - administration & dosage; Celecoxib - pharmacokinetics; Chromatography, High Pressure Liquid - methods; Dexmedetomidine; Dexmedetomidine - administration & dosage; Dexmedetomidine - pharmacokinetics; Dezocine; Dogs; Drug dosages; Drug Therapy, Combination; FDA approval; Fentanyl; Flow velocity; Formic acid; Gastrointestinal surgery; Heart surgery; High performance liquid chromatography; Laboratory animals; Laparoscopy; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Methods; Midazolam; Nonsteroidal anti-inflammatory drugs; Organic acids; Original Research; Pain management; Pharmaceuticals; Pharmacokinetics; Pharmacology; Plasma; Positive ions; Public transportation; Reproducibility of Results; Sleep; Tandem Mass Spectrometry - methods; Tetrahydronaphthalenes - administration & dosage; Tetrahydronaphthalenes - pharmacokinetics; uplc-ms/ms; Ventilation; Ventilators
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S314562

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. 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. 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. 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.