Residual contamination in nebulization medication cups after corticosteroid administration: an in vitro assessment with implications for equine doping control.

Research Overview

• This study evaluated whether residual corticosteroid contamination remains in nebulization medication cups after administration, potentially leading to inadvertent doping in horses.
• It found that although cleaning significantly reduces contamination, trace corticosteroids were still detectable, suggesting separate cups should be used for regulated and non-regulated drugs.

Background and Rationale

• Nebulization is a common method for administering respiratory medications to horses, including corticosteroids.
• Corticosteroids are regulated substances in equine doping control, and their accidental presence in biological samples can have serious consequences.
• There is a concern that residual corticosteroids may remain in nebulizer medication cups after use, risking cross-contamination when cups are reused for non-regulated substances.
• This study aimed to assess the extent of residual corticosteroid contamination and the effectiveness of cleaning procedures in eliminating this contamination.

Study Design and Methods

• The research was performed as an in vitro experimental study, meaning it was conducted outside a living organism under controlled lab conditions.
• Three corticosteroids tested: budesonide, dexamethasone, and fluticasone propionate.
• The corticosteroids were nebulized using Flexineb™ medication cups, which are used clinically for delivering drugs to horses.
• After nebulizing corticosteroids, saline was nebulized through the same cups to simulate subsequent administration of a non-regulated substance.
• Saline nebulization was performed both before and after applying the manufacturer’s recommended cleaning protocol to the medication cups.
• Each experiment was repeated three times using separate medication cups to ensure reliability.
• Samples were collected from:
  • The original corticosteroid formulations.
  • The fluid impacted by nebulization with corticosteroids.
  • The saline nebulized before cleaning (to capture contamination without cleaning).
  • The saline nebulized after cleaning (to measure persistence after cleaning).
• Drug concentrations in samples were quantified using validated analytical methods, ensuring accurate measurement of corticosteroid levels.

Key Findings

• Corticosteroids were detected in all saline samples nebulized after corticosteroid use, regardless of whether cleaning was performed.
• The cleaning procedure significantly reduced residual corticosteroid levels:
  • Budesonide contamination was reduced by more than 99.9%.
  • Dexamethasone contamination was reduced by 95.5%.
  • Fluticasone propionate contamination was reduced by 91.4%.
• Despite reductions, all post-cleaning samples still contained corticosteroid concentrations above the limit of quantification, meaning residual drug traces were clearly present and measurable.

Implications and Recommendations

• This study highlights that even with cleaning, medication cups can retain measurable corticosteroid residues capable of contaminating subsequent nebulized treatments.
• Although an in vitro setup does not directly show how much drug is inhaled or absorbed systemically, any residual contamination poses a doping risk in horses if cups are reused for non-regulated medications.
• The findings suggest that use of separate medication cups for corticosteroid nebulization versus other medications should be considered to avoid inadvertent doping violations.
• Additional research is needed to assess contamination under clinical conditions, including how much residual drug reaches the horse’s lungs and circulatory system and whether this leads to positive doping tests.
• Limitations of this study include:
  • It did not measure the volume of fluid recovered from nebulization.
  • Only a limited number of corticosteroid formulations, cleaning protocols, and cup materials were evaluated.
  • No direct assessment of inhaled doses or biological absorption was performed.

Summary

• This study provides valuable evidence that corticosteroids can persist in nebulizer cups after use, despite cleaning, risking contamination of subsequent respiratory treatments.
• It advises caution in reusing medication cups for different substances in equine practice, especially where doping control is relevant.
• Adopting separate nebulization equipment for regulated corticosteroids and non-regulated drugs can help minimize inadvertent contamination and false doping results.