A UHPLC-MS/MS method for the determination of NSAIDs in bovine milk, featuring a novel standard addition approach to validation for both authorised and unauthorised analytes

Non-steroidal anti-inflammatory drugs (NSAIDs) are compounds that suppress inflammation in a manner similar to steroids but with fewer side effects. Consumption of animal-derived food products containing these residues may present a risk to human health, and therefore it is a requirement to monitor for their presence. This study presents a method that was developed for the semi-quantitative screening (<i>n</i> = 24) and confirmation (<i>n</i> = 22) of NSAID drug residues in bovine milk, using the phosphate modification to QuEChERS (p-QuEChERS) based extraction and analysis by UHPLC-MS/MS. The method was validated according to CIR (EU) 2021/808 with a detection capability (CCβ) of 2.5 µg kg^-1 for all analytes, excluding diclofenac (0.05 µg kg^-1), dihydroketoprofen (0.25 µg kg^-1) and ibuprofen (5 µg kg^-1). Additionally, decision limits (CCα) were calculated for 22 analytes based on a standard addition approach, in accordance with EURL guidance. This publication expands on the previously reported work from this laboratory in validation of confirmatory methods by standard addition to include a novel approach to CCα calculation for unauthorised analytes.