Trace analysis of acidic pharmaceutical residues in waters with isotope dilution gas chromatography–mass spectrometry via methylation derivatization

Abstract Acidic pharmaceutical residues are pollutants of emerging concern and are generally monitored by HPLC–MS/MS. However, due to the limited separation efficiency of HPLC column and lack of suitable mass transition for confirmation analysis, some interference may not be separated completely and differentiated from ibuprofen, which may cause the results with interference, especially in sample with complex matrix. The objective of this study is to develop a sensitive and reliable method for the determination of acidic pharmaceutical residues in water samples by GC–MS with better resolution by using methylation derivatization and isotope dilution techniques. TMSDM, a mild reagent, was used as the derivatization reagent coupling with the isotope dilution technique, for the first time, to improve the precision and accuracy of the analytical method to determine the pharmaceutical residues in water. The MDLs for the five acidic organic compounds: ibuprofen, gemfibrozil, naproxen, ketoprofen and diclofenac were from 0.7 to 1.1 ng/L, with recoveries ranging from 93 to 110%. Alternative to the HPLC–MS/MS method, the developed GC–MS protocols provides an additional option for the analysis of acidic pharmaceutical residues in water, with better separation efficiency in reducing interferences from complicated sample matrix, for determination of ibuprofen residues.