Table S1. Precursor and product ion combinations (quantifier underlined) used to monitor lidocaine and its metabolites by LC-MS/MS in positive mode, including their respective mass spectrometry parameters. Component DMA 4-OH-DMA Precursor ion (m/z) Product ion (m/z) DPa CEb CXPc 122.1 105.0 31 23 8 77.0 31 37 12 121.1 81 21 8 77.0 81 33 12 138.0 DMA-D6 128.0 111.1 56 23 8 MEGX 207.3 58.1 36 17 8 77.2 36 75 4 MEGX-D5 212.2 63.1 31 19 8 LIDO 235.1 86.1 61 23 8 58.0 61 49 10 LIDO-D10 245.2 96.2 66 25 8 3-OH-LIDO 251.1 86.1 56 23 8 58.0 56 53 10 86.1 61 23 8 58.1 61 51 8 91.1 60 33 13 4-OH-LIDO 3-OH-LIDO-D5 a 251.3 256.2 : DP: declustering potential (in volts), b: CE: collision energy (in volts), c: CXP: collision exit potential (in volts) Table S2. Milk production by the cows during different intervals, expressed in kg Time 3-h Exp. 48-h Exp. after injection (h) Cow 1 Cow 2 Cow 3 Cow 4 Cow 5 Cow 6 Cow 7 Cow 8 -0.2 1.0 0.2 0.4 0.8 0.26 0.83 0.94 0.10 0.5 0.4 0.1 0.1 0.8 0.13 0.35 0.23 0.45 1 0.3 0.1 0.2 0.5 0.07 0.07 0.12 0.15 2 3.9 0.2 0.1 0.3 0.77 0.17 0.14 0.16 3 0.6 0.1 0.3 1.1 - - - - 4 1.83 5.93 0.74 8.74 8 13.27 3.52 8.43 5.74 12 10.55 0.75 5.06 1.50 24 23.90 16.60 13.02 16.20 36 6.23 10.64 12.82 11.73 48 21.55 15.10 13.37 15.22 Table S3. Urine production by the cows during different intervals, expressed in kg Time 48-h Exp. after injection (h) Cow 5 Cow 6 Cow 7 Cow 8 -0.25 0.58 1.82 0.51 6.91 3 0.95 5.12 4.00 5.45 6 2.78 6.92 2.83 3.50 9 3.14 5.22 2.88 2.63 12 2.62 4.98 3.39 4.57 24 7.83 17.39 12.89 13.18 36 10.26 14.33 7.39 11.00 48 14.50 29.29 7.00 10.41 Table S4. Tissue and organ weights at slaughter 3-h Experiment Tissue/organ weight (kg) Cow 1 Cow 2 Cow 3 Cow 4 0.71 0.82 0.80 0.92 13.49 11.34 10.30 12.90 Kidneya 1.62 1.89 1.84 2.22 Longissimus dorsia 4.22 3.44 2.94 5.54 Perinephric fat 4.71 0.58 0.33 1.18 Injection site paralumbar fossa Liver 48-h Experiment Cow 5 Cow 6 Cow 7 Cow 8 1.95 1.36 0.72 1.09 14.02 12.62 10.05 11.29 Kidneya 2.34 2.35 2.12 1.78 Longissimus dorsia 4.53 3.44 3.86 4.97 Perinephric fat 1.43 0.60 0.98 2.78 Injection site paralumbar fossa Liver a Only one kidney or muscle from one side Figure S1. Concentrations of lidocaine and metabolites in milk samples of individual cows injected with lidocaine and killed after 48 h.