## 2 Materials and Methods
### Selection of Anticancer Drugs and Their Quantification
\begin{table}
\begin{tabular}{l c c c c c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multicolumn{2}{c}{**CAS Registry**} & \multirow{2}{*}{**Molecular**} & \multirow{2}{*}{**Molecular**} & \multirow{2}{*}{**Structure**} & \multirow{2}{*}{**p\(K_{\text{a}}\)**} & \multirow{2}{*}{**log\(P\)**} & \multicolumn{1}{c}{**Action**} \\  & & **Number** & & & **Formula** & & **Mass (g/mol)** & & **Mechanism** \\ \hline Bicalutamide & \multirow{2}{*}{90357-06-5} & \multirow{2}{*}{C\({}_{18}\)H\({}_{14}\)F\({}_{\text{a}}\)N\({}_{2}\)O\({}_{4}\)S} & \multirow{2}{*}{430.4} & \multirow{2}{*}{**90357-06-5**} & \multirow{2}{*}{**11.5**} & \multirow{2}{*}{4.1} & Antiadrogens \\ (BLT) & & & & & & & & \\ Tamoxifen & \multirow{2}{*}{10540-29-1} & \multirow{2}{*}{C\({}_{28}\)H\({}_{29}\)NO} & \multirow{2}{*}{371.5} & \multirow{2}{*}{**90357-06-5**} & \multirow{2}{*}{**8.7**} & \multirow{2}{*}{5.1} & Antiestrogens \\ (TAM) & & & & & & & \\ \hline Cyclophosphamide & \multirow{2}{*}{50-18-0} & \multirow{2}{*}{C\({}_{7}\)H\({}_{5}\)Cl\({}_{2}\)N\({}_{2}\)O\({}_{2}\)P} & \multirow{2}{*}{261.1} & \multirow{2}{*}{**90357-06-5**} & \multirow{2}{*}{**2.8**} & \multirow{2}{*}{0.2} & Nitrogen \\ (CP) & & & & & & & & \\ \hline Capecitabine & \multirow{2}{*}{154361-50-9} & \multirow{2}{*}{C\({}_{15}\)H\({}_{22}\)FN\({}_{3}\)O\({}_{6}\)} & \multirow{2}{*}{359.4} & \multirow{2}{*}{**90357-06-5**} & \multirow{2}{*}{**5.4**} & \multirow{2}{*}{1.0} & Pyrimidine \\ (CAP) & & & & & & & \\ Doxiflutidine (DFUR) & \multirow{2}{*}{3094-09-5} & \multirow{2}{*}{C\({}_{5}\)H\({}_{11}\)FN\({}_{2}\)O\({}_{5}\)} & \multirow{2}{*}{**246.2**} & \multirow{2}{*}{**90357-06-5**} & \multirow{2}{*}{**7.6**} & \multirow{2}{*}{\(-0.7\)} & Pyrimidine \\ Tagafur (TGF) & & & & & & & \\ \hline CAS: chemical abstracts service; p\(K_{\text{a}}\): logarithmic acid dissociation constant; & log\(P\): octanol-water partition coefficients.  
\end{table} 
Table 3: Details of the target anticancer drugs typified by their action mechanisms (reconstructed based on the data listed in [41]). For quantitative analysis of CP and TAM, gas chromatography (GC) combined with mass spectrometry (MS) was used initially after purification and derivatization [42; 43; 44]. Recent in-depth quantification of these drugs together with the other anticancer drugs was achieved by the simultaneous combination of procedures known as solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS/MS) [16; 45; 46; 47], with special care taken for differences in the protocols applied for the liquid and the solid samples. The concentration and purification steps of the anticancer drugs in the liquid samples were performed by SPE [13; 31]. In the case of the river sediments and the suspended solids (solid state samples), solvent extraction of the adsorbed materials was achieved by sonication and filtration [31; 48; 49] prior to analysis. The final step of measurement was to separate and quantify the target pharmaceuticals by the LC-MS/MS system equipped with an appropriate PC for regulation and calculation. The optimized MS/MS parameters are summarized in Table 4. The cone voltages for detection of the hormone antagonists (BLT and TAM) were somewhat higher than the other anticancer drugs, while lower cone voltages were adequate for the analysis of the antimetabolites (CAP, DFUR, and TGF), which have similar pyrimidine-analogous structures. Quantification of the anticancer drugs was done by subtracting the blank data from the data given by the spiked sample solutions for accounting matrix effects and loss during sample extraction [30; 50]. Similarly, recovery rates were calculated from the deviations between the spiked data and the standard data to perform calibration. Recovery rates varied in the range of 63-124% for river water, 52-116% for STP effluent, 23-112% for river sediment, and 33-122% for suspended solids. These values were mostly similar to the values previously reported for pharmaceuticals in river and sewage samples [48; 51].