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Journal of chromatography. B, Analytical technologies in the biomedical and life sciences2017; 1061-1062; 270-274; doi: 10.1016/j.jchromb.2017.07.024

Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC-MS/MS detection: Development and validation of new methodology.

Abstract: Vitacoxib is an imidazole derivative and the novel COX-2 selective inhibitor to be marketed for veterinary use as nonsteroidal anti-inflammatory drugs. No analytical assay to quantify vitacoxib in equine plasma samples has been published to date. In the current study, we aim to develop and validate a brief, quick and sensitive UPLC-MS/MS method for quantification of vitacoxib in equine plasma samples. Plasma samples were precipitated with methyl tert-butyl ether. The Phenomenex column (Kinetex 50×2.1mm i.d. particle size=2.6μm, C18, 100Å) at 25°C was used in chromatographic separation with mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at flow rate of 0.4mL/min. Vitacoxib and internal standard (IS, celecoxib) were detected under the multiple-reaction monitoring mode by mass spectrometer with ESI+ (m/z 347.9/269.03 for vitacoxib and m/z 382.0/362.0 for IS, respectively). The curve concentration range of was 0.5-500ng/mL with a lower limit of quantification 0.5ng/mL (r=0.996309) in equine plasma samples. The selectivity, precision, recovery, accuracy, matrix effect and stability under various conditions were conformed to the acceptance requirements. Pharmacokinetic studies of vitacoxib in horses via oral administration (0.1mg/kg) demonstrated that the procedure was fully validated and successfully. A meaningful basis for assessing the vitacoxib or clinical applications of vitacoxib to horse is provided in the present study.
Publication Date: 2017-07-15 PubMed ID: 28759842DOI: 10.1016/j.jchromb.2017.07.024Google Scholar: Lookup
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Summary

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The research discusses the development of an efficient method to measure levels of vitacoxib, a new anti-inflammatory drug for pets, in horse blood plasma using Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS).

Development of the Vitacoxib Detection Method

  • The researchers created and tested a rapid and sensitive method to quantify vitacoxib in equine plasma samples using Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS).
  • Plasma samples were treated with methyl tert-butyl ether to precipitate the substances in them, including vitacoxib and celecoxib, used as an internal standard to help measure vitacoxib.
  • A Phenomenex column was involved in the chromatographic separation, with a mixture of acetonitrile and water (containing 0.1% formic acid) used as the mobile phase, flowing at a rate of 0.4mL/min.

Detection of Vitacoxib and Internal Standard

  • Vitacoxib and celecoxib were detected under multiple-reaction monitoring mode by mass spectrometer.
  • The researchers used ElectroSpray Ionisation (ESI+) with a mass-to-charge ratio (m/z) of 347.9/269.03 for vitacoxib and 382.0/362.0 for the internal standard.
  • The concentration of vitacoxib that could be detected ranged from 0.5 to 500ng/mL in horse plasma samples, with a lower limit of 0.5ng/mL.

Validation and Pharmacokinetic Studies

  • The team confirmed various properties of the method, such as its selectivity, precision, recovery rate, accuracy, and stability under different conditions, were fully satisfactory as per acceptance requirements.
  • They conducted pharmacokinetic studies by administering 0.1mg/kg of vitacoxib orally to horses, evaluating how the drug is absorbed, distributed, metabolised, and excreted by the organism.

Implications of the Study

  • This research delivers a vital basis for evaluating the application and effectiveness of vitacoxib in horses.
  • Such information is critical as the drug, which is an imidazole derivative and selective inhibitor of COX-2 enzyme, has been labelled for veterinary use as a non-steroidal anti-inflammatory drug (NSAID), but so far no such detection method has been published.

Cite This Article

APA
Wang J, Zhao T, Kong J, Peng H, Lv P, Li J, Cao X, Zhang S. (2017). Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC-MS/MS detection: Development and validation of new methodology. J Chromatogr B Analyt Technol Biomed Life Sci, 1061-1062, 270-274. https://doi.org/10.1016/j.jchromb.2017.07.024

Publication

ISSN: 1873-376X
NlmUniqueID: 101139554
Country: Netherlands
Language: English
Volume: 1061-1062
Pages: 270-274
PII: S1570-0232(17)30671-2

Researcher Affiliations

Wang, Jianzhong
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
Zhao, Tingting
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
Kong, Jingyuan
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
Peng, Haoyuan
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
Lv, Pengyue
  • Beijing Orbiepharm Co. Ltd., Beijing 100185, People's Republic of China.
Li, Jing
  • Beijing Orbiepharm Co. Ltd., Beijing 100185, People's Republic of China.
Cao, Xingyuan
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China; Key Laboratory of Detection for Veterinary Drug Residue and Illegal Additive, Ministry of Agriculture, Beijing 100193, People's Republic of China. Electronic address: cxy@cau.edu.cn.
Zhang, Suxia
  • Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China; Key Laboratory of Detection for Veterinary Drug Residue and Illegal Additive, Ministry of Agriculture, Beijing 100193, People's Republic of China. Electronic address: suxia@cau.edu.cn.

MeSH Terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Cyclooxygenase 2 Inhibitors / blood
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacokinetics
  • Drug Stability
  • Horses
  • Imidazoles / blood
  • Imidazoles / chemistry
  • Imidazoles / pharmacokinetics
  • Limit of Detection
  • Linear Models
  • Pyridines / blood
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics
  • Reproducibility of Results
  • Sulfones / blood
  • Sulfones / chemistry
  • Sulfones / pharmacokinetics
  • Tandem Mass Spectrometry / methods

Citations

This article has been cited 3 times.
  1. Wang J, Kong J, Yang Y, Liu Y, Qiu J, Gong X, Zhang L, Li J, Sun F, Cao X. Pharmacokinetics, Tissue Distribution, Metabolism and Excretion of a Novel COX-2 Inhibitor, Vitacoxib, in Rats. Front Vet Sci 2022;9:884357.
    doi: 10.3389/fvets.2022.884357pubmed: 35464368google scholar: lookup
  2. DemİrtÜrk E, Nemutlu E, Şahİn S, Öner L. Development and validation of an HPLC method for determination of rofecoxib in bovine serum albumin microspheres. Turk J Chem 2020;44(3):647-655.
    doi: 10.3906/kim-1912-45pubmed: 33488183google scholar: lookup
  3. Wang J, Schneider BK, Xiao H, Qiu J, Gong X, Seo YJ, Li J, Mochel JP, Cao X. Non-Linear Mixed-Effects Pharmacokinetic Modeling of the Novel COX-2 Selective Inhibitor Vitacoxib in Cats. Front Vet Sci 2020;7:554033.
    doi: 10.3389/fvets.2020.554033pubmed: 33102567google scholar: lookup