The ketamine (KET) and its analogs consumed by humans are becoming emerging contaminants (ECs), as they at present in surface waters after being carried through wastewater systems. Drugs in wastewater can be analyzed using the direct-injection method, a simple wastewater analysis (WWA) method that can provide objective, continuous and nearly to real-time findings. This article describes an ultra-high-pressure liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous quantification and confirmation of seven KET-based ECs in wastewater by direct injection. After optimization of the UPLC–MS/MS and sample pretreatment conditions, the method was validated and applied to samples (n = 157) collected from several wastewater treatment plants (WWTPs) in southern China in which KET had the highest detection rate. The established direct-injection method was not only simple to perform but also had better sensitivity, shorter detection times, and analyzed more KET-based ECs than currently published methods, meeting the requirements for the monitoring and high-throughput analysis of common KET-based ECs. We also analyzed the fragmentation pathway of KET-based ECs to obtain product ion information on other unknown substances. Additional studies are needed to establish a comprehensive direct-injection screening method of ECs in wastewater on model-based assessment.
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