# Assessment of Human Pharmaceuticals in Drinking Water Catchments, Tap and Drinking Fountain Waters
## 3 Results and Discussion  
### Analytical Quality Control  
Analytical quality control was performed encompassing different performance criteria such as sensitivity, linear range, matrix effects (ME), accuracy and precision (Table S4, Supplementary Materials). Linearity was studied analyzing in triplicate six concentration levels, using standard solutions between 20 and 250 ng mL\({}^{-1}\), that correspond, according to the analytical methodology, to the range of 10 to 125 ng L\({}^{-1}\), and also in matrix-matched calibrations, at the same concentrations. Linearity, achieved for every compound in the working standard solutions, was reliable as shown by the fact that the correlation coefficients (\(r^{2}\)) ranged from 0.9989, for E1 and 1, for CIT. In matrix-matched solutions, \(r^{2}\) values ranged between 0.9987, for E1 and 1, for CIT.  
MEs equaled the percentage of the matrix-matched calibration slope (B) divided by the slope of the standard calibration in solvent (A). Thus, the ratio (B/A \(\times\) 100) was defined as the absolute matrix effect (ME%). The obtained value was interpreted as follows: a value of 100% denoted an absence of MEs, above 100% signal enhancement and below 100% signal suppression. MEs were considered negligible, since the values varied from 93.55 to 102.68%, for IBU and E2, respectively.  
The method detection (MDLs) and quantification limits (MQLs) were estimated through the matrix-matched calibration curve as 13.35y/x1/b and 110 Sy/x1/b, respectively, where b is the slope and Sy/x the residual standard deviation of the linear function. MDL and MQL values ranged from 1.13 to 5.45 ng L\({}^{-1}\), and from 3.41 to 16.53 ng L\({}^{-1}\), for CIT and E1, respectively (Table 1).  
\begin{table}
\begin{tabular}{l c c c c} \hline \hline
**Therapeutic Group/Compound** & **Matrix-Matched** & **Matrix Effect** & **MDL** & **MQL** \\  & **Linearity (\(r^{2}\))** & **(\%)** & **(ng L\({}^{-1}\))** & **(ng L\({}^{-1}\))** \\ \hline
**Antibiotics** & & & & \\ \hline Azithromycin (AZI) & 0.9995 & 100 & 3.29 & 9.97 \\ Ciprofloxacin (CIP) & 0.9988 & 100.96 & 5.26 & 15.93 \\ Clarithromycin (CLA) & 0.9999 & 98.77 & 1.51 & 4.58 \\ Erythromycin (ERY) & 0.9991 & 98.84 & 4.49 & 13.60 \\ \hline
**Lipid regulators** & & & & \\ \hline Bezafibrate (BEZ) & 0.9998 & 100.00 & 2.26 & 6.84 \\ Gemfibrozil (GEM) & 0.9994 & 94.02 & 3.78 & 11.46 \\ \hline
**Antiepileptic** & & & & \\ \hline Carbamazepine (CAR) & 0.9992 & 101.27 & 4.22 & 12.80 \\ \hline
**Selective serotonin reuptake inhibitors (SSRIs)** & & & & \\ \hline Citalopram (CIT) & 1.0000 & 100.00 & 1.13 & 3.41 \\ Fluoxetine (FLU) & 0.9999 & 100.61 & 1.84 & 5.59 \\ Sertraline (SER) & 0.9996 & 99.44 & 3.04 & 9.22 \\ \hline Non-steroidal anti-inflammatory drugs (**NSAIDs**) & & & & \\ \hline Diclofenac (DIC) & 0.9991 & 101.96 & 4.61 & 13.97 \\
4-hydroxydiclofenac (4-OH-DIC) & 0.9990 & 99.33 & 4.92 & 14.92 \\ (metabololite) & 0.9994 & 93.55 & 3.66 & 11.09 \\ Naproxen (NAP) & 0.9992 & 101.27 & 4.38 & 13.27 \\ Paracetamol (PARA) & 0.9995 & 99.20 & 3.57 & 10.82 \\ \hline
**Hornones** & & & & \\ \hline Estrone (E1) & 0.9987 & 100.68 & 5.45 & 16.53 \\ (natural hormone/metabolite) & 0.9991 & 102.68 & 4.56 & 13.82 \\
17\(\omega\)-ethinylestradiol (EE2) & 0.9990 & 99.44 & 4.94 & 14.98 \\ \hline \hline \end{tabular}
\end{table}
Table 1: Matrix-matched linearity, matrix effect, method detection limits (MDLs), method quantification limits (MQLs) of the selected pharmaceuticals.  
Recovery tests were performed to determine the accuracy and precision of the method by spiking a surface water at three levels, 20, 60 and 125 ng L\({}^{-1}\) (n = 3), in three different days, and each sample was analyzed in triplicate. Accuracy, determined using the matrix-matched calibration curve, varied between 94.02 and 99.88%; as for precision, evaluated through the relative standard deviation (RSD) of intra-day and inter-day repeatability, was below 8.70 and 6.85%, respectively. These values are considered reliable and similar to other methods developed for the same purpose [4; 23; 24].