# Pharmaceuticals in Coastal Waters: An UHPLC-TOF-MS Multi-Residue Approach
## 1 Introduction
Therefore, considering the importance of having reliable methods capable of surveying a wide number of pharmaceuticals in seawater, with the possibility of revisiting results for untargeted compounds, the present work describes the development and validation of an UHPLC-TOF-MS method to screen and quantify a large suite of pharmaceuticals in estuarine and coastal waters. Specifically, this method targeted 63 drugs (including amoxicillin, ciprofloxacin, sulfamethoxazole, trimethoprim and venlafaxine from the WFD Watch List) from 8 therapeutic classes of pharmaceuticals: 38 antibiotics, 1 analgesic, 3 non-steroidal anti-inflammatory (NSAIDs), 5 antidepressants, 4 \(\beta\)-blockers, 5 lipid regulators, 3 anticonvulsants and 4 antihypertensive drugs (Table 1). This selection was based on annual reports of the most prescribed and sold human medicines in Portugal [12] and their predicted environmental behavior. The method described will provide an important tool in environmental monitoring of pharmaceuticals in coastal ecosystems with varying salinity gradients, allied to post-analytical survey. \begin{table}
\begin{tabular}{l l c c c c c c c c c c} \hline \hline
**Compound** & **Molecular** & **LogP** & **Molecular** & **IM + HI\({}^{*}\)** & **AM** & **LoD** & **LoQ** & **Repeatability** & **Reproducibility** & **Recovery** & **RT (min)** \\  & **Formula** & **Weight** & **[M + HI\({}^{*}\)** & **(ppm)** & **(ng/J)** & **(ng/J)** & **(\%)** & **(\%)** & **(\%)** & **(\%)** & **RT (min)** \\ \hline \(\beta\)-Blocars & C\({}_{41}\)H\({}_{23}\)N\({}_{\rm O}\)\({}_{3}\) & 0.57 & 266.1630 & 287.1703 & –0.7 & 0.01 & 0.03 & 3.0\% & 4.2\% & 104.4\% & 3.47 \\ Disoprolol & C\({}_{58}\)H\({}_{21}\)N\({}_{\rm O}\)\({}_{1}\) & 2.30 & 325.2253 & 236.2326 & –1.0 & 0.14 & 0.46 & 8.3\% & 9.1\% & 94.7\% & 5.29 \\ Carevidoli & C\({}_{24}\)H\({}_{23}\)N\({}_{\rm O}\)\({}_{4}\) & 3.05 & 406.1892 & 407.1965 & –0.9 & 0.83 & 2.76 & 13.4\% & 19.7\% & 108.7\% & 5.87 \\ Propranolol & C\({}_{41}\)H\({}_{21}\)N\({}_{\rm O}\)\({}_{2}\) & 3.03 & 259.1572 & 260.1645 & –0.6 & 0.06 & 0.21 & 4.5\% & 6.5\% & 100.9\% & 4.39 \\ Lipid regulators & & & & & & & & & & \\ Advvastatin & C\({}_{30}\)H\({}_{58}\)N\({}_{\rm O}\)\({}_{3}\) & 4.24 & 559.2803 & 559.2603 & 0.6 & 8.92 & 29.73 & 7.9\% & 10.2\% & 88.6\% & 8.46 \\ Benzidbrate & C\({}_{59}\)H\({}_{22}\)C\({}_{10}\)N\({}_{4}\) & 3.97 & 362.1154 & 362.1154 & –0.8 & 0.07 & 0.24 & 7.4\% & 8.6\% & 85.7\% & 6.91 \\ Fondbroixen & C\({}_{59}\)H\({}_{22}\)N\({}_{\rm O}\)\({}_{4}\) & 4.86 & 361.1201 & 361.1201 & 0.7 & 0.02 & 0.06 & 17.2\% & 18.1\% & 103.5\% & 9.41 \\ Gembroix & C\({}_{59}\)H\({}_{23}\)N\({}_{\rm O}\) & 3.61 & 251.1642 & 215.1642 & –0.8 & 0.21 & 0.71 & 4.5\% & 6.8\% & 110.4\% & 4.99 \\ Smvastatin & C\({}_{58}\)H\({}_{38}\)O\({}_{3}\) & 4.51 & 419.2792 & 419.2792 & –1.6 & 2.80 & 9.34 & 11.7\% & 12.2\% & 110.3\% & 6.20 \\ NSAIDs & & & & & & & & & & \\ Dickofenac & C\({}_{41}\)H\({}_{11}\)C\({}_{30}\)N\({}_{2}\) & 4.98 & 295.0166 & 296.024 & –0.5 & 0.02 & 0.05 & 5.9\% & 8.8\% & 106.0\% & 7.70 \\ Ibuprofen & C\({}_{33}\)H\({}_{50}\)\({}_{2}\) & 3.50 & 206.1306 & 207.138 & –0.4 & 2.72 & 9.08 & 3.5\% & 5.3\% & 108.9\% & 6.22 \\ Nimesulfide & C\({}_{33}\)H\({}_{21}\)N\({}_{5}\)O\({}_{5}\) & 2.56 & 308.0166 & 309.054 & 0.3 & 0.03 & 0.08 & 7.4\% & 11.1\% & 104.5\% & 7.23 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._