Determination of Carbamazepine and Its Metabolites in Aqueous Samples Using Liquid Chromatography−Electrospray Tandem Mass Spectrometry

Abstract

A quantitative method is described for solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous analysis of carbamazepine and its five metabolites, 10,11-dihydro-10,11-epoxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, 2-hydroxycarbamazepine, 3-hydroxycarbamazepine, and 10,11-dihydro-10-hydroxycarbamazepine. An SPE procedure was used to concentrate target compounds from aqueous samples collected from sewage treatment plant (STP) wastewater and surface water. Extracts were analyzed using electrospray LC-MS/MS with time-scheduled selected reaction monitoring. The recoveries of the analytes were 83.6-102.2% from untreated sewage (influent), 90.6-103.5% from treated sewage (effluent), and 95.7-102.9% from surface water samples. The instrumental detection limits were 0.8-4.8 pg for the analytes. Matrix effects were investigated for the analytes in HPLC-grade water, surface water, and STP influent and effluent. Ion suppression increased for analytes in order of surface water to STP effluent to STP influent, but no ion suppression was observed for analytes in HPLC-grade water. The developed method was validated by analysis of environmental aqueous samples: STP influent and effluent and surface water. Carbamazepine and all five metabolites were detected in STP influent and effluent samples. Only carbamazepine and 10,11-dihydro-10,11-dihydroxycarbamazepine were detected in the surface water sample. Notably, 10,11-dihydro-10,11-dihydroxycarbamazepine was detected at approximately 3 times higher concentrations than the parent drug, carbamazepine, in all of the aqueous samples. To our knowledge, this is the first report on the simultaneous determination of carbamazepine and its metabolites in environmental samples.