Application Note # LCMS-73 Interlaboratory Tests Demonstrate the Robustness and Transferability of the Toxtyper™ Workflow Abstract There is high demand in clinical and forensic toxicology for comprehensive, specific and transferable techniques that overcome the well-known limitations of current GC-MS, LC-UV/DAD and immunoassay solutions. Liquid chromatography-tandem mass spectrometry (LC-MS) combined with library searching is an emerging screening solution for toxicology. Here we describe a robust and automated solution for the detection and identification of drugs and drugs of abuse in biological specimens. The workflow was tested with regard to method- and result-transferability from lab to lab. Authors Jürgen Kempf, Laura Huppertz, Susanne Vogt Institut für Rechtsmedizin, Universitätsklinikum Freiburg, Germany Markus Meyer, Sebastian Götz, Birgit Schneider Bruker Daltonik GmbH, Bremen, Germany Keywords Instrumentation and Software Library Search amaZon speed Toxicology Screening Compass OpenAccess 1.4 Drug Screening DA 4.1 Drugs of Abuse Ion Trap

Introduction LC-MS/MS is an emerging screening solution for clinical, routine and forensic toxicology. This method is far more specific than routinely used immunoassays and provides more information and higher identification rates than LC-UV/DAD detection (Application Note LCMS-72). Compared to GC-MS, LC-MS promises to cover a more comprehensive range of analytes. Due to the availability of large spectral libraries (see Ref. 1) and a high degree of transferability of results from lab to lab, GC-MS is currently regarded as the gold standard in toxicology for general unknown screening (GUS). However,...

Library search and reporting The data sets were post-processed using DataAnalysis (DA) 4.1 and the processed spectra were submitted to the DA 4.1 library search module. The whole process, up to final report generation and visualization of results in the web-based Compass OpenAccess interface, was driven by a predefined Toxtyper automation script. The automatically generated reports from the different labs were evaluated and used for generation of the final result tables. Sample Preparation SPE or LLE OpenAccess software for sample management Data acquisition by LC-MSn on amaZon speed Results...

and Mirtazapine not only have very similar retention times, but also differ only slightly in mass (2 Da). This problematic combination of characteristics can be regarded as a very rare case. Common false positives were identified in the blank serum sample and the other samples, but these could be easily excluded after manual inspection of the reports and the respective raw data files. For example, a common false positive was benzododecinium. This compound is used as skin disinfectant during blood withdrawal and is present in the sample as a contaminant. The first page of the result report is...

Result reporting of interlaboratory test serum 2 Submitter abderrahim karmime Station Amazon Supervisor System Administrator Base Peak Chromatogram Base peak chromatogram - positive ionization mode Time [min| Base peak chromatogram - negative ionization mode Library Search Results cmp£ Purity' RT[minl d RT [min] m/z [Dal d m'z [Da] Intensity Search result table Figure 2: Result reports can be accessed by the web or sent by e-mai

Detailed MS and MS2 spectra results of the Toxtyper reporting for Amitryptilin Cmpd 7, AutoMS" (278.14), 4.89 min, Amitriptyline Compound Spectra Figure 3: Result reports can be accessed by the web or sent by e-mail

Transferability of MS∕ MS fragmentation results from lab–to–lab Intens. [%] 30 RV Serum 2_1280_RB6_01_1001.d: +MS2(278.10), 4.73-4.78min #2108-2139 Score 980 20 105.04 10 0 [%] 30 117.00 91.06 128.25 91.12 129.02 117.09 91.17 191.02 155.07 129.08 104.84 116.84 205.00 218.09 231.11 RV Se 2_1580_RD7_01_2027.d: +MS2(277.94), 4.94-4.96min #2334-2343 HUG 2 190.82 154.76 233.74 90.92 128.84 204.78 178.86 140.79 217.84 120724_RV SE 2_665_BD7_01_10663.d: +MS2(278.21), 4.72min #2159 Score 989 104.97 20 190.90 154.90 116.92 90.94 128.89 IKC 233.96 204.93 178.92 140.87 217.98 231.03 RV Se 2_160_RD5_01_271.d:...

[1] Hans H. Maurer, Karl Pfleger, Armin A. Weber: Mass Spectral and GC Data of Drugs, Poisons, Pesticides, Pollutants and Their Metabolites (2011) Bruker Daltonics is continually improving its products and reserves the right [2] Birgit Schneider, Carsten Baessmann, Sebastian Götz, Arnd Ingendoh (2009): “Zero Dealy” Polarity Switching for Ultra-fast MS/MS Screening Applications; Bruker Application Note LCMS-51 #264574 [3] Jürgen Kempf, Laura Huppertz, Susanne Vogt (Universitätsklinikum Freiburg, Germany), Markus Meyer, Sebastian Götz, Birgit Schneider (Bruker DaltoniK GmbH, Germany) (2012): Toxtyper...