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Drug testing and analysis2021; 14(2); 252-261; doi: 10.1002/dta.3174

LC-HRMS/MS study of the prodrug ciclesonide and its active metabolite desisobutyryl-ciclesonide in plasma after an inhalative administration to horses for doping control purposes.

Abstract: Ciclesonide (CIC) is the first inhaled highly potent corticosteroid that does not cause any cortisol suppression. It has been developed for the treatment of asthma in human and more recently in equine. CIC is the active compound of Aservo® EquiHaler® (Boehringer Ingelheim Vetmedica GmbH), the pre-filled inhaler generating a medicated mist based on Soft Mist™ technology. This prodrug is rapidly converted to desisobutyryl-ciclesonide (des-CIC), the main pharmacologically active compound. Due to its anti-inflammatory properties, CIC is prohibited for use in horse competitions. To set up an appropriate control, the determination of detection times and screening limits are required. Therefore, a highly sensitive analytical method based on supported liquid extraction (SLE) combined with liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) was developed to detect CIC and its active metabolite des-CIC in plasma. The lower limit of detection of CIC and des-CIC was approximately 1 pg/ml in plasma. After a pilot study conducted on a single horse at the recommended dose (eight actuations twice daily corresponding to 5.5 mg/day for the first 5 days, followed by 12 actuations once daily corresponding to 4.1 mg/day in the last 5 days), the same protocol was applied in the main study using six horses. In all horses, CIC and des-CIC levels were less than 5 and 10 pg/ml, respectively, at 36 h after the end of the administration. The outcome of this risk assessment study should be useful to draw any recommendations for horse competitions.
© 2021 John Wiley & Sons, Ltd.
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Publication Date: 2021-10-30 PubMed ID: 34634175DOI: 10.1002/dta.3174Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores the use of a potent corticosteroid, ciclesonide (CIC), in treating equine asthma and the method of detecting it in horse plasma for doping control purposes after the inhalation of the drug.

Objective of the Research

The researchers’ main aim is to identify the concentration of CIC and its active metabolite, desisobutyryl-ciclesonide (CIC-des), in horse plasma. They also want to establish a detection time and screening limits for the presence of CIC in the horse’s body to put up a proper control system against its use in horse competitions due to its powerful anti-inflammatory properties.

Methodology

  • A highly sensitive analytical method was constructed to detect CIC and des-CIC. This was a combination of supported liquid extraction and liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS).
  • The experiment was trialed on a single horse. The horse was given the recommended dosage of the medication: eight actuations twice a day (equivalent to 5.5mg per day) for the first five days, then 12 actuations once a day (equivalent to 4.1mg/day) for the last five days.
  • The same protocol was then applied to six more horses.

Results and Findings

  • Additionally, the lower limit of detection for CIC and des-CIC was approximately 1 pg/ml in horse plasma. After inhalation, the prodrug CIC was rapidly converted into des-CIC, the primary pharmacologically active compound.
  • In all horses, CIC levels and des-CIC levels were below the specified 5 and 10 pg/ml, respectively, 36 hours after the last dosage.

Significance of the Research

  • The findings from this risk assessment study can give direction for implementing regulations in horse competitions. This study’s results will be beneficial in preventing the misuse of the drug for enhanced performance in horse competitions, protecting the integrity of the sports industry.
  • Moreover, it highlights the efficacy of the LC-HRMS/MS method in detecting minimal traces of the corticosteroid, CIC and its metabolite in horse plasma, which can help develop optimal detection techniques.

Cite This Article

APA
Trevisiol S, Moulard Y, Kaabia Z, Delcourt V, Loup B, Garcia P, Boyer S, Dauriac K, Groseille G, Rouger S, Narbe R, Popot MA, Bailly-Chouriberry L. (2021). LC-HRMS/MS study of the prodrug ciclesonide and its active metabolite desisobutyryl-ciclesonide in plasma after an inhalative administration to horses for doping control purposes. Drug Test Anal, 14(2), 252-261. https://doi.org/10.1002/dta.3174

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 14
Issue: 2
Pages: 252-261

Researcher Affiliations

Trevisiol, Stéphane
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Moulard, Yves
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Kaabia, Zied
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Delcourt, Vivian
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Loup, Benoit
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Garcia, Patrice
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Boyer, Sophie
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Dauriac, Karine
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Groseille, Guillaume
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Rouger, Sébastien
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Narbe, Ruediger
  • Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
Popot, Marie-Agnès
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Bailly-Chouriberry, Ludovic
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.

MeSH Terms

  • Animals
  • Chromatography, Liquid / methods
  • Horses
  • Pilot Projects
  • Pregnenediones / analysis
  • Prodrugs

Grant Funding

  • Boehringer Ingelheim

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