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wastewaterbased epidemiology wbe widely implemented around world complementary tool conventional surveillance techniques inform improve public health responses currently wastewater surveillance programs us evaluating integrated approaches address public health challenges across multiple domains including substance abuse work demonstrated potential online solidphase extraction coupled liquid chromatographyhighresolution mass spectrometry support targeted quantification nontargeted analysis psychoactive lifestyle substances step toward understanding operational feasibility statewide wastewater surveillance program substance use assessment new york target screening confirmed 39 substances influent samples collected 10 wastewater treatment plants varying sewershed characteristics anticipated meet throughput demands statewide program scales full capacity nontarget screening prioritized additional compounds identification three confidence levels including psychoactive substances opioid analgesics phenethylamines cathinone derivatives consumption rates 12 target substances detected 80 wastewater samples similar reported previous usbased wbe studies despite uncertainty associated backcalculations selected substances relative bias consumption estimates sensitive variations monitoring frequency factors beyond human excretion eg indicated parenttometabolite ratios might also contribute prevalence sewershed scale overall study marks initial phase refining analytical workflows data interpretation preparation incorporation substance use assessment statewide wastewater surveillance program new york