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Drug testing and analysis2023; 15(6); 629-645; doi: 10.1002/dta.3461

Control of a sulfadoxine/trimethoprim combination in the competition horse: Elimination, metabolism and detection following an intravenous administration.

Abstract: The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-phase extraction, samples were analysed by liquid chromatography/electrospray ionisation tandem mass spectrometry in positive ionisation mode. The applied multiple reaction monitoring (MRM) method allowed the detection of SDO and TMP with a lower limit of detection of 0.03 ng/mL in plasma and 0.2 (SDO) and 0.4 ng/mL (TMP) in urine, respectively. In the present study, detection times for SDO were 15 days in plasma and 49 days in urine, respectively. TMP was detected for up to 7 days in plasma and up to 50 days in urine, respectively. The detection via the TMP metabolite 3-desmethyl-trimethoprim was possible for 70 days in urine. Detection times of the other confirmed metabolites N -acetylated sulfadoxine, hydroxytrimethoprim, trimethoprim-1-oxide and trimethoprim-3-oxide were significantly lower. In order to postulate reasonable screening limits (SLs) to control specific withdrawal times, a Monte Carlo simulation was performed for SDO. The proposed SL of 10 ng/mL SDO in blood and 300 ng/mL urine corresponds to a detection time of 4 days.
© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
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Publication Date: 2023-03-22 PubMed ID: 36806946DOI: 10.1002/dta.3461Google 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.

This research study investigates the excretion and detection times of the drugs sulfadoxine (SDO) and trimethoprim (TMP), which are commonly used in veterinary medicine. The researchers administered these drugs to horses and measured the amount present in their plasma and urine over a period of time.

Study Methodology

  • The study involved eight horses that were administered a single intravenous dose of 2.7mg TMP and 13.4mg SDO per kg of bodyweight.
  • Plasma and urine samples were collected from each horse for up to 15 days and 70 days post-administration, respectively.
  • Urine samples were treated with an enzymatic process, while plasma samples were proteolysed, which involves breaking down proteins into smaller polypeptides or amino acids.
  • Following a solid-phase extraction process, the samples were then analysed using liquid chromatography/electrospray ionisation tandem mass spectrometry. This is a technique commonly used to separate, identify and quantify each component in a mixture.
  • The researchers used a multiple reaction monitoring method, with the aim of detecting SDO and TMP with a lower limit of detection of 0.03ng/mL in plasma and 0.2 (SDO) and 0.4ng/mL (TMP) in urine.

Study Findings

  • The study found that detection times for SDO were 15 days in plasma and 49 days in urine. An additional metabolite of TMP, known as 3-desmethyl-trimethoprim, could be detected for up to 70 days in urine.
  • However, the detection times for other confirmed metabolites – N-acetylated sulfadoxine, hydroxytrimethoprim, trimethoprim-1-oxide and trimethoprim-3-oxide – were significantly lower.
  • The researchers carried out a Monte Carlo simulation, a mathematical technique used to predict the probability of different outcomes, in order to recommend screening limits for these drugs. They suggested a screening limit of 10ng/mL SDO in blood and 300ng/mL urine, which corresponds to a detection time of 4 days.

This research provides valuable insights into detection and excretion times for the widely used veterinary drugs SDO and TMP. This information is important for ensuring the ethical and healthy use of these drugs in competition horses.

Cite This Article

APA
Schenk I, Broussou D, Roques B, Lagershausen H, Machnik M, Röttgen H, Toutain PL, Thevis M. (2023). Control of a sulfadoxine/trimethoprim combination in the competition horse: Elimination, metabolism and detection following an intravenous administration. Drug Test Anal, 15(6), 629-645. https://doi.org/10.1002/dta.3461

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 15
Issue: 6
Pages: 629-645

Researcher Affiliations

Schenk, Ina
  • Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
Broussou, Diane
  • INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
Roques, Beatrice
  • INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
Lagershausen, Henrike
  • German Equestrian Federation, Warendorf, Germany.
Machnik, Marc
  • Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
Röttgen, Helma
  • Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
Toutain, Pierre-Louis
  • INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
  • Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.
Thevis, Mario
  • Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.

MeSH Terms

  • Horses
  • Animals
  • Trimethoprim / analysis
  • Sulfadoxine / analysis
  • Chromatography, Liquid
  • Administration, Intravenous
  • Chromatography, High Pressure Liquid

Grant Funding

  • German Equestrian Federation e.V.
  • Manfred Donike Institute for Doping Analysis e.V.

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