Characterizing and compensating for matrix effects using atmospheric pressure chemical ionization liquid chromatography-tandem mass spectrometry: analysis of neutral pharmaceuticals in municipal wastewater.

Matrix effects are a great challenge for the quantitative analysis of environmental samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Signal suppression or enhancement can compromise the accuracy of analytical results. While matrix effects have been relatively well studied for applications of LC-MS/MS instrumentation with electrospray ionization, there have been relatively few studies to evaluate matrix effects when using atmospheric pressure chemical ionization (APCI) as the ion source. In this study, we determined the effects of sample matrix on the analysis of six neutral pharmaceuticals (i.e., caffeine, cotinine, carbamazepine and its major metabolite, carbamazepine-10,11-dihydrodiol, trimethoprim, and fluoxetine) in samples of municipal wastewater using LC-APCI-MS/MS and evaluated whether isotope-labeled internal standards can be used to compensate for matrix effects. The matrix effects were measured using postextraction spikes and postcolumn direct infusion, respectively. The results showed that the matrix in the extracts prepared from municipal wastewater enhanced the signals for four of the six analytes when using an APCI source. Without correction for signal enhancement, apparent recoveries of the analytes from wastewater samples were overestimated to levels as high as 178% of the spiked amount. Isotope-labeled compounds corrected for these overestimates that occurred as a result of interferences from the sample matrix.