Fentanyl, a potent µ-opioid analgesic, is commonly used in veterinary medicine, including to provide appropriate analgesia for orthopaedic injuries on-track and it’s permanently banned in greyhound racing, unless administered by a veterinarian for pain relief (greyhounds must still present to race free of the substance). This study aimed to characterise the pharmacokinetics of transdermal fentanyl in greyhounds, inform risk management, aid appropriate reporting criteria for racing chemists, and guide veterinarians in determining appropriate withdrawal times.
Six greyhounds were administered a Duragesic® patch (fentanyl 100µg/h) for 120 hours. Plasma and urine samples were collected over eight days.
Plasma (0.5 mL) or hydrolysed urine (1 mL) was subject to solid phase extraction (SPE) then analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with fentanyl-d5 and norfentanyl-d5 as internal standards for quantification. The limit of detection/quantification for analytes was estimated to be 0.01/0.1 ng/mL in plasma and 0.1/1.0 ng/mL in urine from validation that also assessed specificity, accuracy, precision, recovery and matrix effects.
Non-compartmental analysis was used for determination of pharmacokinetic parameters. Plasma concentrations reached therapeutic concentrations in 12-24 hours and steady-state (~0.5 ng/mL) at 48 hours, declining post-removal with geometric mean half-life of 10 hours; five times longer than a comparative IV study due to a five times larger volume of distribution. Norfentanyl, the inactive metabolite, showed greater variability and no advantage over fentanyl for regulatory purposes.
Using Toutain methodology, an irrelevant plasma concentration (IPC) of 1 pg/mL and urine concentration (IUC) of 0.5 ng/mL were derived. Extrapolated detection times were 4 days for both matrices. Monte Carlo simulations confirmed withdrawal time of 8 days would cover >99% of predicted detection times. Although IPC/IUC are determined, screening limits may not be appropriate for banned substances, or necessary given those requiring opiate analgesia on welfare grounds have a recuperation time longer than detection time.