Ketoprofen in ruminants, pigs and equids: the end of the “No MRL required” status — 50 µg/kg in muscle and kidney, 20 µg/kg in milk; HPLC-UV with an LOQ of 50 µg/kg is no longer sufficient
Commission Implementing Regulation (EU) 2025/1105, published on 4 June 2025, replaces in Table 1 of the Annex to Regulation (EU) No 37/2010 the classification “No MRL required” with numerical maximum residue limits for ketoprofen in all ruminants, pigs and equids. It is based on the recommendation of the European Medicines Agency of 7 November 2024, issued after a review the Commission requested in March 2023.
- New MRLs (marker residue — ketoprofen): muscle 50 µg/kg, fat 20 µg/kg (for pigs skin and fat in natural proportions), liver 20 µg/kg, kidney 50 µg/kg, milk 20 µg/kg. The poultry entry is unchanged: muscle 10, skin and fat 30, liver 10, kidney 10 µg/kg, not for use in animals producing eggs for human consumption.
- Methods: the CVMP found that the existing HPLC-UV method for bovine tissues and equine muscle (LOD 25 µg/kg, LOQ 50 µg/kg) is not sensitive enough for the new MRLs. The EU Reference Laboratory for residues of veterinary drugs has UHPLC-MS/MS methods for acidic NSAIDs: ketoprofen in bovine and equine muscle in the range 0.5–10 µg/kg, in bovine milk 5–60 µg/kg, robust to changes in, among others, operator, storage time, SPE cartridge batch and column batch.
- Why: the calculated consumer exposure exceeded the ADI (5 µg/kg bw per day, 0.3 mg per person) 4–12 h after treatment in cattle and 3–12 h in pigs, and — when the injection site is considered — still at 24–48 h. A 4-day withdrawal period is sufficient, but according to the CVMP MRL status cannot depend on withdrawal periods, and without MRLs there is no legal basis to control and prosecute illegal use. With the new MRLs the theoretical intake is below 55 % of the ADI.
- Metabolism: after intramuscular administration of 3 mg/kg bw to calves, ketoprofen accounted for 56 % of residues in muscle and kidney, 35 % in fat and 2 % in liver; in a study with ¹⁴C-ketoprofen, 90–93 % of urinary radioactivity was due to the metabolite RP 69400. The MRLs from cattle and pigs were extended to all ruminants and equids under Regulation (EU) 2017/880.