## 2 Materials and Methods
### Estimation of Sorption Distribution Coefficient (Log\(K_{d}\)) and Mass Balance  
The sorption distribution coefficients (log\(K_{d}\)) between the liquid samples and the solid samples were determined as log(\(C_{\rm s}\)/\(C_{\rm w}\)) in accordance with the previous reports [54; 55], where \(C_{\rm s}\) (ng/kg) is the concentration of pharmaceuticals in the solid samples and \(C_{\rm w}\) (ng/L) is the concentration of pharmaceuticals in the liquid samples.  
Experimental sorption of the target anticancer drugs onto the river sediments was done separately by following the procedure as described previously [56; 57; 58] as well as OECD guideline No. 106 [59]. Sediment samples were suspended in ammonium acetate buffer (pH 7) containing a known amount of the anticancer drugs (0-200 ug/L), and the mixtures were shaken reciprocally for 24 h at 20 \({}^{\circ}\)C in the  
\begin{table}
\begin{tabular}{l c c c c c c} \hline \hline
**Compound** & \begin{tabular}{c} **Retention** \\ **Time (min)** \\ \end{tabular} & \begin{tabular}{c} **Precursor** \\ **Ion (m/z)** \\ \end{tabular} & \begin{tabular}{c} **Product Ion** \\ **(m/z)** \\ \end{tabular} & \begin{tabular}{c} **Cone** \\ **Voltage (V)** \\ \end{tabular} & \begin{tabular}{c} **Collision** \\ **Energy (eV)** \\ \end{tabular} & \begin{tabular}{c} **Ionization** \\ **Mode** \\ \end{tabular} \\ \hline \hline \begin{tabular}{l} Bicaltumamide \\ (BLT) \\ \end{tabular} & 14.8 & 429.3 & 255.2 & 30 & 16 & – \\ \begin{tabular}{l} Tamoxifen (TAM) \\ \end{tabular} & 17.9 & 372.4 & 72.3 & 45 & 15 & + \\ \hline \begin{tabular}{l} Cyclophosphamide \\ (CP) \\ \end{tabular} & 10.2 & 261.2 & 106.2, 139.9, & 35 & 15 & + \\ \hline \begin{tabular}{l} Capecitabine \\ (CAP) \\ \end{tabular} & 12.4 & 360.4 & 174.2, 244.2 & 25 & 16 & + \\ \
\begin{tabular}{l} Dosifluridine \\ (DFUR) \\ \end{tabular} & 2.0 & 247.2 & 73.0, 99.1, 117.0 & 15 & 12 & + \\
\begin{tabular}{l} Tegafur (TGF) \\ \end{tabular} & 2.8 & 201.2 & 71.0, 131.1 & 15 & 18 & + \\ \hline \hline \end{tabular}
\end{table}
Table 4: LC-MS/MS parameters for the target anticancer drugs (reproduced from [30]).  
dark to prevent photolysis [56; 57]. After incubation, each solution was recovered by filtration through a GD/X glass fiber filter and the concentrations of the anticancer drugs were measured by LC-MS/MS. In the cases for the experimental sorption, the log\(K_{\mathrm{d}}\) values for the river sediment were determined from the slope of the linear regression lines produced by the initial and equilibrated concentrations in the dissolved phase and the dry weight of the adsorbent [24; 60; 61].  
For estimation of the mass balance of the target anticancer drugs discharged into the Kanzaki-Ai River basin, the mass flux (g/day) of each anticancer drug at each site was calculated by multiplying the detected concentration by the mean river flow rate or the mean STP discharge rate in terms of m\({}^{3}\)/day. The flow rates at the sampling sites are listed in Tables 1 and 2. Total mass flux for each drug was calculated by numerical summation of the mass flux values from the upstream region to the farthest downstream boundary site at the Suita Bridge (R5). The mass balance of each drug was then estimated as a percentage of the mass flux for that drug at this boundary site.