A SPE-LC-MS/MS Method for the Detection of Low Concentrations of Pharmaceuticals in Industrial Waste Streams

Abstract

A SPE-LC-MS/MS method was developed and validated for the determination of three active pharmaceutical ingredients [API A (3-([2-(diaminomethyleneamino)thiazol-4-yl]methylthio)-N′-sulfamoyl propanimid amide, API B 5-[(2 R)-2-[2-(2-ethoxyphenoxy)ethylamino]propyl]-2-methoxybenzenesulfonamide hydrochloride, API C 1-azabicyclo[2.2.2]octan-8-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate] in the wastewater of a chemical synthesis production facility. The SPE-LC-MS/MS method was validated in actual influent and effluent samples. Linearity, LOD, LOQ, repeatability, intermediate precision, and recovery were determined. An LOQ of 400 μg · L⁻¹, 1.0 μg · L⁻¹, and 6 μg · L⁻¹, repeatability of 2.5% CV, 14.8% CV, and 11.9% CV, intermediate precision of 7.8% CV, 11.0% CV, and 8.7% CV and SPE recovery of 114%, 103%, and 91% was determined for API A, B, and C, respectively, in influent. An LOQ of 400 μg · L⁻¹, 0.8 μg · L⁻¹, and 6 μg · L⁻¹, repeatability of 2.0% CV, 11.0% CV, and 10.9% CV, intermediate precision of 1.7% CV, 6.8% CV, and 10.2% CV and SPE recovery of 116%, 96%, and 115% was established for API A, B, and C, respectively, in effluent. Coefficients of correlation for each analyte were >0.9301 confirming the linearity of the method. The LC-MS/MS method was used for an on-going monitoring program for these pharmaceuticals in wastewater. The method development techniques, validation procedures, and results from real wastewater samples are presented in this paper.

Keywords:

• Mass spectrometry
• Pharmaceuticals
• Solid phase extraction
• Wastewater

Acknowledgments

This research project was financially supported by Science Foundation Ireland (SFI, 07/RFP/EEEOBF768) and Questor Centre (DCU2/07/10).