Paper Spray Ionization Coupled to High Resolution Tandem Mass Spectrometry for Comprehensive Urine Drug Testing in Comparison to Liquid Chromatography-Coupled Techniques after Urine Precipitation or Dried Urine Spot Workup.

Screening procedures using high resolution (HR)-mass spectrometry (MS) are getting more and more important, e.g., for drug testing or adherence monitoring. Approaches usually include time-consuming sample preparation and compound separation by liquid chromatography (LC). The paper spray ionization (PSI) technique coupled to MS might overcome these steps by direct analysis of complex mixtures without extraction and separation. In recent years, this technology proved its potential for quantification and/or qualitative screening in biofluids. However, so far, PSI-MS was only applied to procedures covering a limited number of targets. Therefore, a PSI-HR-MS/MS approach was developed and successfully validated for comprehensive urine screening. The procedure showed high matrix effects for most drugs but still acceptable limits of identification. Applicability was tested by analyses of three proficiency tests for systematic toxicological analysis and of 103 authentic human urine samples. Its screening power was compared to that of published LC-HR-MS/MS procedures after urine precipitation with conjugate cleavage (UglucP) or dried urine spot workup by conjugate cleavage and liquid extraction (DUSglucE). In the authentic samples, 73% of all 777 drug intakes were detectable with the new approach. The LC-HR-MS/MS screening approaches detected more drugs, particularly in samples with low analyte concentrations, with values of 88% after UglucP or 76% after DUSglucE. In conclusion, the new PSI-HR-MS/MS screening approach was suitable for comprehensive urine screening of different drug classes and might be a promising alternative to conventional procedures. However, limitations should be considered such as detection of drugs in low concentrations and risk of false positive or negative results caused by mixed spectra.