## 3 Results and Discussion  
### Method Validation  
All of the validated API parameters were assessed against the range established by USGS method No. 5-B10 (matrix recovery of 60-130% and RSD \(\leq\)20%) and the determined analytical limits (Table 2) were all in the ng/L range [7]. Mean calibration r\({}^{2}\)-values were 0.984 \(\pm\) 0.019, relative standard deviation of intra- and inter-day repeatability and precision was typically \(\leq\)20% (Table S5), and recovery from LCMS-grade water (Table S6), tap water (Table S7), surface water (Table S8), WWTP effluent (Table S9) and WWTP influent (Table S10) were typically between 60-130%. Analyte response (i.e., recovery) was comparable between LCMS-grade water, drinking water and surface water with deviation from a range of 60-130% most notable in WWTP influent (67% of determinations). This is likely due to matrix enhancement and indicates that analysis of WWTP influent may be best conducted with an initial sample clean-up method or by analysis following dilution of the sample using methods described by [PERSON] et al. [7]. Limits of detection were lowest in LCMS-grade water and highest in WWTP influent (Table S11). Generally, little difference was observed between the analytical limits determined in LCMS-grade water and those in tap and surface water enabling sensitive use of the method with these matrices (Table 2).  
This validation indicates that the method presented here is sufficiently robust and is best used in high-throughput applications for analysis of drinking and surface water. The method can also be applied with reasonable accuracy in non-diluted WWTP effluent. While analysis of influent water is possible, dilution is recommended on a site-specific basis due to potential matrix effects. The precision of the analysis in influent samples may be improved with further sample pre-treatment such as solid phase extraction [16].  
The analytical response and limits demonstrated by this method are comparable to (e.g., [PERSON] et al. [7], [PERSON] et al. [17], [PERSON] et al. [18]) and more sensitive than (e.g., [PERSON] et al. [8]) other direct-injection HPLC-MS/MS methods. This supports similar work demonstrating that direct-injection HPLC-MS/MS can achieve robust and specific quantification at low ng/L levels without a need for sample clean-up (other than filtration) and pre-concentration [16]. Furthermore, this method provides similar environmentally relevant sensitivity as more rigorous (and likely more expensive) protocols involving sample pre-concentration and SPE (e.g., [PERSON] et al. [19], [PERSON] et al. [20]). The protocol presented here also offers a clear advantage over others as the shipment and chemical stability of the selected contaminants during shipment was also validated, as shown in Section 3.2. Therefore, use of this protocol allows for sample collection in areas geographically isolated from analytical centres, which may reduce the accessibility barriers to sensitive analytical equipment worldwide.  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Validation Parameter** & \multicolumn{2}{c}{**Mean \(\pm\) SD**} & **Within Acceptable Range \({}^{*}\)** \\ \hline Linearity & r\({}^{2}\) & 0.984 \(\pm\) 0.02 & \\ \hline \multirow{3}{*}{Intra-day Repeatability (\%)} & 10 ng/L & 29 \(\pm\) 19 & 46\% \\  & 100 ng/L & 11 \(\pm\) 9 & 82\% \\  & 1000 ng/L & 8 \(\pm\) 6 & 95\% \\ \hline \multirow{3}{*}{Intermediate/Inter-day Precision (\%)} & 10 ng/L & 42 \(\pm\) 41 & 34\% \\  & 100 ng/L & 16 \(\pm\) 12 & 72\% \\ \cline{1-1}  & 1000 ng/L & 9 \(\pm\) 6 & 93\% \\ \hline \hline \end{tabular}
\end{table}
Table 2: Statistical overview of method validation showing the mean value and standard deviation (SD) for each parameter and the percent of determinations which fall between the acceptable range employed by U.S. Geological Survey (USGS) Method No. 5-B10.