## 2 Material and Methods
### Analysis of CECs
#### 2.3.3 Instrumentation  
HRMS-MS analyses were performed at MORAS research center of UDJG, with an Ultra-Mate 3000 UHPLC System (Thermo Fisher Scientific), coupled with a Q Exactive-OrbitrapTM mass spectrometer equipped with Heated Electrospray Ionization (HESI) probe (Thermo Fisher Scientific). Chromatographic separation used a Syncronis C18 column (50 mm \(\times\) 2.1 mm, 1.7 \(\mu\)m) at 30 \({}^{\circ}\)C. A 15 min gradient elution at a 0.3 mL/min flow rate solvent A (water with 0.01% formic acid) and solvent B (methanol with 0.01% formic acid) was used for quantitative LC-HRMS-MS analysis. Full scan MS followed by data dependent MS2 (ddMS2) in both positive and negative mode was used for quantitative analysis of the selected compounds listed in Table 1.  
Parameters for MS analysis were set as follows. The applied voltage was 3.6 kV, and the capillary temperature was 320 \({}^{\circ}\)C for positive ionization. Negative mode ionization used a spray voltage of 2.9 kV and a capillary temperature of 300 \({}^{\circ}\)C. The normalized collision energy (NCE) of the cell was set at 35 eV in both positive and negative mode. Nitrogen was used as collision and auxiliary gas, at flow rates of 10 and 40 arbitrary units, respectively, with a temperature of 350 \({}^{\circ}\)C. Full scan covered the 100-1000 \(m/z\) range; data were acquired at a resolving power of 70,000 FWHM at 200 \(m/z\), while a resolution of 35,000 was used for MS-MS analysis. The Automatic Gain Control (AGC) target was set to 10\({}^{6}\), with the maximum injection time of 200 ms. The scan rate was set at 3.7 scan/s. The precursor ions are filtered by the quadrupole which operates at an isolation window of 2 \(m/z\). \begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline
**Component** & **Class** & **Formula** & **Exact Mass** & **DM + BI-** & **DM + BI-** & **RF** & **MS-MS Fragments** & **Recovery C/C** & **LOO +E/** & **LOO +E/** & **LOO +E/** \\ \hline Salimethosavande & Salimethos & CuffiN/OGS & 253,0821 & 254,090 & 252,0488 & 5.23 & 108,485,156,0135,92,0866 & 90.5 & 1 & 3 \\ Transception & Damitosynthesis & CuffiN/OGS & 290,13799 & 291,1461 & 299,1306 & 4.58 & 220,1168,123,166,240,1302 & 100.2 & 1.5 & 3.7 \\ \hline Cyndonova & Quizdens & CuffiN/OGS & 331,1332 & 332,1649 & 330,1289 & 4.28 & 20,188,208,138,203,2005 & 95.8 & 1.9 & 5.7 \\ \hline Markowitz & Quizdens & CuffiN/OGS & 339,1332 & 330,1644 & 338,1259 & 4.12 & 20,188,208,138,203,203,2036 & 95.4 & 2.8 & 6.9 \\ \hline Flamequine & Flamequine & CuffiN/OGS & 264,0881 & 282,0053 & 260,0728 & 6.25 & 244,069,220,4897,30,2020 & 91 & 3.2 & 9.7 \\ \hline Cyndonville & Terasymmetric & CuffiN/OGS & 464,1451,1584 & 46,1584 & 499,149 & 4.46 & 184,052,182,183,115,084 & 50.2 & 8 & 24.3 \\ Daycycline & Terasymmetric & CuffiN/OGS & 444,152,452 & 465,146,1400 & 6.53 & 186,057,152,082,193,082 & 97 & 88.5 & 28.6 \\ \hline Amoxicillin & Antibiotic & CuffiN/OGS & 365,1045 & 366,1117 & 364,0972 & 3.39 & 180,043,114,079 & 63.5 & 6.7 & 20.1 \\ \hline Germanium & Penofilines & CuffiN/OGS & 542,0688 & 425,070 & **423,068**,063 & 8.12 & 315,084,284,201,307,090 & 87 & 3.2 & 9 \\ \hline Dicksonville & Penofilines & CuffiN/OGS & 469,0235 & 469,038 & 469,0235 & 6.6 & 186,097,198,084 & 96 & 2.4 & 6.8 \\ \hline Chloronyl & Liscussoundes & CuffiN/OGS/GS & 424,1798 & 425,1807 & 423,772,102 & 10.25 & 407,178,377,142,128,1278 & 95 & 5.2 & 15 \\ \hline Chunapureure & Antiprinciple & CuffiN/OGS & 226,0499 & 227,1022 & 225,0697 & 7.45 & 194,096,182,020,179,072 & 108 & 2 & 6.2 \\ \hline Chloride-acid & Light radioactive & CuffiN/OGS & 214,0395 & 254,069 & 255,069 & 253,032,034 & 8.23 & 116,038,055,069,169,067 & 67.5 & 9.5 & 5.7 \\ \hline Presentation & Lipel-lowering & CuffiN/OGS & 42,624,184 & 452,5203 & **633,238** & 5.6 & 321,170,031,036,119,0607 & 98 & 1.2 & 3.7 \\ \hline EpData were processed with the Xcalibur software version 2.1.1. The mass tolerance window was set to 5 ppm.