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. 2021 Jun 15:15:2529-2541.
doi: 10.2147/DDDT.S314562. eCollection 2021.

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

Jie Hu  1   2 , Xin-Juan Su  2 , Hui-Ling Si  2 , Rui-Xiang Song  3 , Fang Zhang  3 , Xiang-Jun Qiu  3 , Xing-Peng Chen  2
Affiliations

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

Jie Hu et al. Drug Des Devel Ther. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Continue.
Figure 1
Figure 1
The chemical structure and the ion transitions from parent ion to daughter ion of CEL, DEZ and DEX (A)-CEL, (B)-DEZ, (C)-DEX.
Figure 2
Figure 2
The representative chromatograms of CEL, DEZ, DEX and IS in positive ion mode. (A) a blank plasma sample; (B) a blank plasma sample spiked with 250 ng/mL CEL, 25 ng/mL DEZ, 2.5 ng/mL DEX and 100 ng/mL IS; (C) a beagle plasma sample 1.5 h after administration.
Figure 3
Figure 3
(A) The mean plasma concentration–time curve of CEL after 6.67 mg/kg CEL oral administration to 6 beagle dogs (n=6). (B) The mean plasma concentration–time curve of DEZ after 0.33 mg/kg DEZ intramuscular administration to 6 beagle dogs (n=6). (C) The mean plasma concentration–time curve of DEX after 2 μg/kg DEX slow intravenous administration to 6 beagle dogs (n=6).
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