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Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in b...

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Autores principales: Hu, Jie, Lv, Bing-feng, Guo, Wen-jing, Wang, Bo-wen, Miao, Di, Qiu, Xiang-jun, Chen, Xing-peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428950/
https://www.ncbi.nlm.nih.gov/pubmed/32832543
http://dx.doi.org/10.1155/2020/1563874
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author Hu, Jie
Lv, Bing-feng
Guo, Wen-jing
Wang, Bo-wen
Miao, Di
Qiu, Xiang-jun
Chen, Xing-peng
author_facet Hu, Jie
Lv, Bing-feng
Guo, Wen-jing
Wang, Bo-wen
Miao, Di
Qiu, Xiang-jun
Chen, Xing-peng
author_sort Hu, Jie
collection PubMed
description A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1 → 119.1 for parecoxib, m/z 313.0 → 118.0 for valdecoxib, and m/z 380.0 → 316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 μg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 μg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. C(max) of parecoxib in group A and group B was 2148.59 ± 406.13 ng/mL and 2100.49 ± 356.94 ng/mL, t(1/2) was 0.85 ± 0.36 h and 0.85 ± 0.36 h, and AUC((0‐t)) was 2429.96 ± 323.22 ng·h/mL and 2506.38 ± 544.83 ng·h/mL, respectively. C(max) of valdecoxib in group A and group B was 2059.15 ± 281.86 ng/mL and 2837.39 ± 276.78 ng/mL, t(1/2) was 2.44 ± 1.55 h and 2.91 ± 1.27 h, and AUC((0‐t)) was 4971.61 ± 696.56 ng·h/mL and 6770.65 ± 453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. C(max) and AUC((0 − ∞)) of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t(1/2) was increased from 2.44 h to 2.91 h. V(z)/F and CL(z)/F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib.
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spelling pubmed-74289502020-08-20 Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS Hu, Jie Lv, Bing-feng Guo, Wen-jing Wang, Bo-wen Miao, Di Qiu, Xiang-jun Chen, Xing-peng Biomed Res Int Research Article A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1 → 119.1 for parecoxib, m/z 313.0 → 118.0 for valdecoxib, and m/z 380.0 → 316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 μg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 μg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. C(max) of parecoxib in group A and group B was 2148.59 ± 406.13 ng/mL and 2100.49 ± 356.94 ng/mL, t(1/2) was 0.85 ± 0.36 h and 0.85 ± 0.36 h, and AUC((0‐t)) was 2429.96 ± 323.22 ng·h/mL and 2506.38 ± 544.83 ng·h/mL, respectively. C(max) of valdecoxib in group A and group B was 2059.15 ± 281.86 ng/mL and 2837.39 ± 276.78 ng/mL, t(1/2) was 2.44 ± 1.55 h and 2.91 ± 1.27 h, and AUC((0‐t)) was 4971.61 ± 696.56 ng·h/mL and 6770.65 ± 453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. C(max) and AUC((0 − ∞)) of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t(1/2) was increased from 2.44 h to 2.91 h. V(z)/F and CL(z)/F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib. Hindawi 2020-08-06 /pmc/articles/PMC7428950/ /pubmed/32832543 http://dx.doi.org/10.1155/2020/1563874 Text en Copyright © 2020 Jie Hu et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hu, Jie
Lv, Bing-feng
Guo, Wen-jing
Wang, Bo-wen
Miao, Di
Qiu, Xiang-jun
Chen, Xing-peng
Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title_full Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title_fullStr Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title_full_unstemmed Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title_short Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS
title_sort effects of dexmedetomidine on the pharmacokinetics of parecoxib and its metabolite valdecoxib in beagles by uplc-ms/ms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428950/
https://www.ncbi.nlm.nih.gov/pubmed/32832543
http://dx.doi.org/10.1155/2020/1563874
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