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

Autor: Schenk I; Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany., Broussou D; INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France., Roques B; INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France., Lagershausen H; German Equestrian Federation, Warendorf, Germany., Machnik M; Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany., Röttgen H; Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany., Toutain PL; INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.; Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK., Thevis M; Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: Drug testing and analysis [Drug Test Anal] 2023 Jun; Vol. 15 (6), pp. 629-645. Date of Electronic Publication: 2023 Mar 22.
DOI: 10.1002/dta.3461
Abstrakt: 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 4 -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.)
Databáze: MEDLINE
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