Abstract. Authors. Forensics: The need for certainty

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1 Application Note LCMS-16 Efficacy of Enhanced Confirmation Criteria to Reduce False Positive Detections in Forensic Screening Using LC-QTOF Mass Spectrometry Abstract A study was undertaken to demonstrate the use of Liquid Chromatography-Quadrupole Time of Flight (LC-QTOF) Mass Spectrometry to screen urine and serum samples for compounds covering a variety of drug classes relevant to post-mortem and routine forensic drug screening. To assess the robustness of this methodology, three independent laboratories used identical hardware configurations to screen for 61 compounds in spiked and authentic forensic case samples. False positive detections were practically eliminated by applying enhanced confirmation criteria based on the concept of diagnostic qualifier ions, resulting in a sensitive and robust toxicological screening method with a low detection threshold. Forensics: The need for certainty In addition to the common drugs of abuse, such as cocaine and cannabis, new psychoactive substances, (also known as designer drugs or legal highs ) are constantly emerging on the international recreational drug scene. The UN Office on Drugs and Crime (UNODC) reported that 348 new legal highs emerged worldwide from 29 to 213.[1] In order to confidently identify the increasing number of substances present in samples, forensic toxicologists require methods that can provide rapid screening over a wide range of compound classes. Authors Petra Decker, Tony Drury, Carsten Baessmann, Bruker Daltonik GmbH, Bremen, Germany 1 Jürgen Kempf, Laura M Huppertz, Volker Auwärter Institute of Forensic Medicine, Department of Forensic Toxicology, Medical Center - University Freiburg, Germany 2 Anna Pelander, Mira Sundstroem, Ilkka Ojanpera Department of Forensic Medicine, University of Helsinki, Finland 3 Keywords Forensic Screening Accurate mass Toxicology Diagnostic ion False positive Instrumentation and Software Bruker impact QTOF Ultimate 3 Rapid Separations LC

2 Moreover, eliminating false positives and false negatives is a key priority, so as to ensure the completeness and accuracy of data such that it can stand up to scrutiny in legal proceedings. High resolution LC-QTOF mass spectrometry has been successfully used in forensic toxicological screening for several years.[2] Inherent characteristics of accurate mass make it an ideal tool for this sector, as it provides sensitive wide scope screening with retrospective and general unknown analysis capabilities. In this application note, a recently developed method using LC-QTOF mass spectrometry was tested for its suitability for routine forensic toxicology screening. The approach described herein incorporates tools for enhanced results confirmation using the diagnostic ion concept. The diagnostic ion concept was tested in urine and serum with spiked and authentic forensic samples to assess the efficiency of removing false positive findings whilst maintaining a low detection threshold. Methods To illustrate the reliability of the screening setup and methods identical hardware configurations were set up to screen urine and serum samples at Bruker Daltonics, Bremen and the forensic laboratories located in 3 Helsinki and 2 Freiburg. Sixty one target compounds were selected for this study as shown in Table 1. These compounds included a variety of compound classes and were selected based on their practical relevance in post-mortem and routine drug screening and their varied physiochemical properties, including exact mass, retention time and fragmentation energy. Table 1: Key forensic compounds investigated 6-Monoacetylmorphine (MAM), 7-Aminoflunitrazepam, 9-Hydroxyrisperidone (Paliperidone), Alprazolam, Amiodarone, Amisulpride, Amitriptyline, Amphetamine, Benzoylecgonine, Bromazepam, Buprenorphine, Citalopram, Cocaethylene, Cocaine, Codeine, Caffeine, Cotinine, Diazepam, Dihydrocodeine, Diphenhydramine, Doxepin, Ecgonine methyl ester, EDDP, Fentanyl, Flunitrazepam, Lamotrigine, MDA, MDMA (Ecstasy), Methadone, Methamphetamine, Midazolam, Mirtazapine, Morphine, Norbuprenorphine, Norcitalopram, Nordazepam, Nordoxepin, Norfentanyl, Nortilidine, Nortrimipramine, Nortriptyline, O-Desmethyltramadol, O-Desmethylvenlafaxine, Olanzapine, Oxazepam, Oxycodone, Paracetamol (Acetaminophen), Paroxetine, Pregabalin, Promethazine, Quetiapine, Risperidone, Strychnine, Temazepam, THC-COOH, Tilidine, Tramadol, Trimipramine, Venlafaxine, Zolpidem, Zopiclone Instrumentation UPLC: Ultimate 3 Rapid Separations LC Column: Acclaim RSLC C x 1 mm, 2.2 µm Temperature: 3 C Mobile phase: A = H 2 O/MeOH 9:1, B = MeOH (both 5 mm NH 4 formate /.1% HCOOH) Gradient: Multistep gradient % in 14 min Flow rate: Flow gradient ml/min Injection: 1 µl MS: Bruker impact QTOF mass spectrometer Scan mode: Full scan TOF MS with broadband Collision Induced Dissociation (bbcid)* Scan range: m/z 3 1. Ionization: ESI +ve 2,5V *Broadband Collision Induced Dissociation (bbcid) Broadband Collision Induced Dissociation (bbcid) is a data acquisition process where both TOF MS full scan data and MS/MS fragments are continuously generated in two independent, rapidly alternating data channels, (cycle time 1Hz) without either precursor ion or threshold selection. Channel 1 TOF MS (low collision energy): Precursor ions are not isolated or fragmented, producing full scan TOF MS spectra across every LC peak. Channel 2 broadband CID (high collision energy): Again, there is no precursor ion isolation but in this instance all ions are fragmented in the collision cell resulting in the generation of bbcid MS/MS spectra across every LC peak. Since the two data channels are continuously acquired across all chromatographic peaks, there is little chance of missing important spectral information in complex matrices. Sample Analysis After protein precipitation with acetonitrile, urine and serum samples were spiked with the compound mixes (1/11 compounds per mix) at four levels (1, 5, 1 and 5 ng/ml) and analyzed on the impact QTOF system in Bremen in TOF-MS and bbcid modes. For automated processing the intensity threshold for compound detection was set to allow detection on all relevant traces in a 1 ng/ml sample in solvent. The total numbers of findings in all samples were collected and compared to the number of expected findings. For the runs acquired in bbcid mode, additional enhanced detection confirmation criteria were applied. In this instance, compounds were only considered as detected when at least one diagnostic ion with RT difference <.5 min of the main compound ion was detected in either the full scan (TOF-MS) or bbcid channel. The same processing method and detection criteria were applied on data acquired from authentic samples from routine cases. These included 11 urine samples from Helsinki autopsy cases and 8 urine / serum samples from

3 a combination of post mortem & roadside testing cases from Freiburg. The results were compared to findings from established routine mass spectrometric screening methods. Results LC Method Suitability In the test mixtures analysed at all three sites, compounds eluted evenly spread across the chromatogram, with good peak shape fidelity for early eluting compounds including those commonly known for chromatographic issues e.g. morphine (Figure 1). For spiked urine and serum samples, the RT reproducibility between the three sites was better than.2 min (.35 min for olanzapine). RT values were stable over the complete sequence and independent from matrix interference (see Figure 2). MS Database The database (DB) was created for the processing of the TOF MS full scan data and contained 73 entries for the 61 compound set. An almost exclusive [M+H] + ionization was observed, with only diphenhydramine, amphetamine and related compounds presenting significant in-source fragmentation whilst for temazepam and pregabalin some sodium adduct formation takes place. Overlay of three chromatograms Figure 1: Overlay of three chromatograms acquired at all three sites for the same compound mix, demonstrating very good system-to-system reproducibility of retention times. Overlay of three chromatograms Figure 2: Retention time stability over time and in spiked matrices: Overlay of four chromatograms for a mix of all 61 compounds in solvent (2 times from start and end of sequence) for urine and serum. a) complete chromatogram, b) expanded chromatogram range ( min).

4 Table 2: Example of extract from the full scan TOF-MS database m/z RT sum formula name C18H21NO3 Codeine C8H1N4O2 Caffeine C9^13CH12N2O Cotinine (^13C) C16H13ClN2O Diazepam C18H23NO3 Dihydrocodeine C17H21NO Diphenhydramine C13H11^1+ Diphenhydr. Fragm C19H21NO Doxepin Conversely, in bbcid mode sufficient fragmentation was achieved by raising the collision energy to 3 ev with +/-6V stepping without precursor selection resulting in simultaneous fragmentation of all ions present. From the bbcid spectra diagnostic qualifier ions (QIs) could be assigned for most compounds as shown in Table 3. Only buprenorphine, norbuprenorphine and strychnine did not show sufficient fragmentation even when using the optimized collision energy settings, so that no QIs could be assigned for these compounds. For 41 compounds three QIs were assigned, two QIs were available for 11 compounds and for the last 6 compounds only one reasonable QI could be assigned. This extended bbcid database contained 136 entries including the M+1 or M+2 isotope trace definitions and bbcid fragment ions. Discussion For the spiked samples all compounds were detected in full scan TOF MS analyses at all concentration levels, with no false negatives being observed. However, if the threshold level for detection was lowered, then many compounds would be detectable even at significantly lower levels. In addition to the expected compounds, a few additional plausible compounds were also detected such as caffeine in blank matrix or analytical artifacts (e.g. cocaine detection in a mix that contains cocaethylene and methanol). However, without applying the enhanced diagnostic confirmation criteria, the number of false positive detections in TOF-MS mode is significantly more than the number of expected findings. In sum for all TOF-MS analyses 333 false positives were detected in serum. This is greater than the 274 expected findings. For the detailed numbers of total, expected and plausible findings, as well as the number of false positives, (see Table 4). In the bbcid channel, all compounds were detected in at least on one of their traces, but after applying the enhanced diagnostic confirmation detection criteria, zopiclone and paracetamol were missed at the 1ng/mL spike level due to the absence of a confirmatory diagnostic qualifier ion. However both zopiclone and paracetamol would have been detected if a lower data processing threshold was used. The false positive rate in urine is even higher due to the increased matrix load and low detection threshold of 75 cts, yielding 547 false positives compared to 276 expected (see Table 4). All serum and urine sample mixes were then reprocessed, but this time with the diagnostic ion enhanced confirmation criteria being applied. Table 5 summarises the results. After applying the enhanced confirmation criteria, with the exception of tramadol, (mix 2), the false positives were completely removed. Tramadol cannot be removed as a finding in the presence of o-desmethylvenlafaxine as they are isobaric, co-elute and have very similar fragmentation patterns (see Figure 5). Table 3: Extract from the full scan bbcid database, detailing additional diagnostic qualifier ions (QIs). m/z RT sum formula name QI 1 QI 2 QI C14N3H1OBr Bromazepam C14N3H1O^81Br Bromazepam (^81Br) C18H21NO3 Codeine C17^13CH21NO3 Codeine (^13C) C1H12N2O Cotinine C9^13CH12N2O Cotinine (^13C) C16H13ClN2O Diazepam C16H13^37ClN2O Diazepam (^37Cl) C17H21NO Diphenhydramine C16^13CH21NO Diphenhydramine (^13C) C13H11^1+ Diphenhydr. Fragm

5 Example of hrxic traces and bbcid spectrum for fentanyl x x1 5 3 Mix5-1_bbCID3_8-12_GE2_1_544.d: FENTANYL, , C 22 H 28 N 2 O 1, 6.min 95. x1 5 FENTANYL (337) a) b) Mix5-1_bbCID3_8-12_GE2_1_544.d: FENTANYL, (bbcid), C 22 H 28 N 2 O 1, Qualifier 15 M+H bbcid MS 2 QI x1 6.8 Mix5-1_bbCID3_8-12_GE2_1_544.d: FENTANYL, (bbcid), C 22 H 28 N 2 O 1, Qualifier m/z.6.4 QI 2.2. x Mix5-1_bbCID3_8-12_GE2_1_544.d: FENTANYL, (bbcid), C 22 H 28 N 2 O 1, Qualifier QI x1 5 Mix5-1_bbCID3_8-12_GE2_1_544.d: FENTANYL (^13C), , C 21 H 28 N 2 O 1 ^13C FENTANYL (^13C) 2 13 C Figure 3: bbcid spectrum (a) and (b) hrxic qualifier ion traces providing unambiguous identification for fentanyl bbcid hrxic traces for tramadol and o-desmethylvenlafaxine x x U_M1_1ppb_bbCID: TRAMADOL, , 4.8min Tramadol (M+H) 264 M+H U_M1_1ppb_bbCID: TRAMADOL, (bbcid), QI1, 4.8min 58 QI m/z 58 x x U_M2_1ppb_bbCID: O-DESMETHYLVENLAFAXINE, , 4.8 min O-Desmethylvenlafaxine (M+H) 264 a) b) U_M2_1ppb_bbCID: O-DESMETHYLVENLAFAXINE, QI1 4.8min C U_M1_1ppb_bbCID: TRAMADOL (^13C), , ^13C, 4.8min Tramadol ^13C U_M2_1ppb_bbCID: O-DESMETHYLVENLAFAXINE, (^13C) 4.8min O-Desmethylvenlafaxine ^13C Time [min] Time [min] Figure 4:bbCID hrxic traces for (a) tramadol and (b) o-desmethylvenlafaxine. Note, that they almost co-elute, have identical monoisotopic mass and a common fragment ion m/z=58

6 bbcid spectra for tramadol and o-desmethylvenlafaxine x MS2( ), eV, min # Tramadol, C 16 H 25 NO 2 bbcid spectrum m/z x bbcid MS, 3.eV, min # (.9 mda), (-.1 mda), (-.2 mda), : points : (-.1), rel. I.21 (-.2), rel. I o-desmethylvenlafaxine, C 16 H 25 NO 2 bbcid spectrum o-desmethylvenlafaxine m/z Figure 5: bbcid spectra for tramadol and o-desmethylvenlafaxine. Note, that the common m/z = 58 fragment ion cannot be used to distinguish tramadol in the presence of o-desmethylvenlafaxine. However, the two QIs circled in green allow for unambiguous identification of o-desmethylvenlafaxine in the presence of tramadol Table 4: Detection statistics for spiked serum samples before applying the diagnostic ion confirmation criteria: SERUM: Full scan SERUM: Full Scan URINE: Full scan URINE: Full Scan (TOF MS) (bbcid) (TOF MS) (bbcid) Conc. [ng/ml] Conc. [ng/ml] Mix Mix Mix Mix Mix Mix Mix Mix Mix Mix Mix Mix TOTALS TOTALS Black: total # of findings, Blue: # expected findings, Green: # plausible positive findings, Red: # remaining false positives

7 Table 5: False Positive detection statistics for (a) spiked serum samples and (b) spiked urine samples after applying the diagnostic ion confirmation criteria: SERUM FALSE POSITIVE FINDINGS (bbcid) Conc. [ng/ml] Mix 1 Mix Mix 3 Mix 4 Mix 5 Mix 6 URINE FALSE POSITIVE FINDINGS (bbcid) Conc. [ng/ml] Mix 1 Mix Mix 3 Mix 4 Mix 5 Mix 6 Screening Results from Authentic Case Samples Authentic case samples from Helsinki and Freiburg were analyzed using an identical analysis protocol and the findings using the accurate mass diagnostic ion concept (DI concept) were compared to results from other established analytical techniques. Authentic urine case x dil x 1_RB1_1_69.d: ALPRAZOLAM, , 8.4min ALPRAZOLAM 39 M+H 954 dil x 1_RB1_1_69.d: ALPRAZOLAM, (bbcid), Qualifier, 8.4min x QI 1. x bbcid MS, 25.eV, min # (-.6 mda), (.2 mda), : points : (-.6), rel. I.7(.2), rel. I bbcid spectrum, sample dil x 1_RB1_1_69.d: ALPRAZOLAM, (bbcid,) Qualifier, 8.4min x m/z QI dil x 1_RB1_1_69.d: ALPRAZOLAM (^37Cl), , 8.4min x15 ALPRAZOLAM (^37Cl) C Time [min] x bbcid spectrum, standard +bbcid MS, eV, m/z Figure 6: Authentic urine case number 954 at Helsinki. Alprazolam is confirmed as an additional finding by QI traces and bbcid spectrum.

8 Authentic case: post-mortem serum and urine samples a) x1 6 COTININE Caffeine GS25-12 HeSe_RA6_1_447.d 1.25 Amphetamine Amphetamine QI m/z = 91 O-DESMETHYLVENLAFAXINE TRAMADOL VENLAFAXINE (^13C) METHADONE (^13C) METHADONE EDDP (METHADONE METABOLITE) 1. Amphetamine QI m/z 119 BENZOYLECGONINE O-DESMETHYLVENLAFAXINE TRAMADOL (^13C) (^13C).75 Amphetamine (^13C) BENZOYLECGONINE (^13C).5 Caffeine (^13C) EDDP (METHADONE METABOLITE) (^13C).25 COTININE (^13C) b). x ECGONINE METHYL ESTER ECGONINE METHYL ESTER (^13C) Amphetamine Amphetamine BENZOYLECGONINE Fragm (^13C) (^13C) Time [min] O-DESMETHYLVENLAFAXINE METHADONE BENZOYLECGONINE (^13C) CARBOXY-THC, , C 21 H 28 CARBOXY-THC (345) CARBOXY-THC, (bbcid), C 21 H 28 O 4, Qual 299 M+H QI 1.75 Caffeine CARBOXY-THC, (bbcid), C 21 H 28 O 4, Qual QI CARBOXY-THC (^13C), , C 2 H 28 O 4 ^13 CARBOXY-THC (^13C) 13 C Time [min] COTININE Amphetamine Coffein (^13C) (^13C) ECGONINE METHYL ESTER Amphetamine - TRAMADOL Fragm 91 CARBOXY - THC Time [min] Figure 7: Authentic case (Freiburg case number GS25). a) post-mortem serum, b) post-mortem urine for same case. hrxic s showing confirmation of trace findings for amphetamine and carboxy-thc using bbcid qualifier ion traces.

9 Table 6: Findings in authentic post-mortem urine samples (Helsinki). Samples were extracted using mixed-mode SPE [3]. Reconstituted samples were diluted 1:1 prior to analysis Case # Compound Detected Additional False (DI concept) Findings Positives 934 Tramadol O-desmethyltramadol NONE Caffeine 936 Methadone EDDP Cotinine NONE Caffeine 943 Zopiclone Paracetamol NONE Caffeine 945 Cocaine Benzoylecgonine Alprazolam NONE Ecgonine methyl ester Caffeine Cocaethylene Citalopram Norcitalopram Zopiclone Temazepam Cotinine 946 Codeine Morphine NONE Tramadol O-desmethyltramadol Paracetamol 954 Pregabalin Alprazolam Carboxy-THC Caffiene EDDP Quetiapine Hydroxyquetiapine Paracetamol Temazepam Oxazepam Cotinine Case # Compound Detected Additional False (DI concept) Findings Positives 956 Pregabalin Citalopram Caffeine NONE Norcitalopram Cotinine Mirtazapine Paracetamol Diazepam Temazepam Oxazepam 962 Citalopram Norcitalopram Caffeine NONE Codeine Morphine Paracetamol Lamotrigine Alprazolam 97 Fentanyl Norfentanyl Paracetamol 974 Zopiclone Diazepam Cotinine NONE Nordazepam Temazepam Oxazepam H382 Fentanyl Oxycodone Norfentanyl NONE Mirtazapine Cotinine Midazolam Nordazepam Oxazepam Caffeine

10 Table 7: Summary for serum and urine authentic case samples (Freiburg). Serum samples were extracted using alkaline liquid-liquid extraction. Urine samples were precipitated with ACN and reconstituted in eluent 5/5.[4] Case# Compound Detected Additional False Result type (DI concept) Findings Positives T Serum, roadside testing Amphetamine 147 ng/ml GC-MS Cotinine NONE Cocaine 1,1 ng/ml GC-MS Caffeine Benzoylecgonine 148 ng/ml GC-MS Ecgonine methyl ester 4, ng/ml GC-MS T12778 Serum roadside testing Cocaine 2, ng/ml GC-MS Cocaethylene NONE Benzoylecgonine 482 ng/ml GC-MS Cotinine Ecgonine methyl ester 48 ng/ml GC-MS Caffeine THC 3,1 ng/ml GC-MS (not in DB) 11-OH-THC 2,2 ng/ml GC-MS (not in DB) THC-COOH 36 ng/ml GC-MS ND * T12116 Serum roadside testing Quetiapine 11 ng/ml LC-MS/MS Cotinine Tramadol Venlafaxine 1 ng/ml LC-MS/MS Caffeine O-desmethylvenlafaxine ca. 5 ng/ml LC-MS/MS Zopiclone T12148 Serum roadside testing Morphine 91 ng/ml LC-MS/MS 6-MAM NONE Codeine 17 ng/ml LC-MS/MS Cotinine Diazepam 41 ng/ml LC-MS/MS Caffeine Nordazepam >1 ng/ml LC-MS/MS Paracetamol Temazepam 22 ng/ml LC-MS/MS Oxazepam 28 ng/ml LC-MS/MS Flunitrazepam 3 ng/ml LC-MS/MS 7-Aminoflunitrazepam 32 ng/ml LC-MS/MS GS 25 Se Post mortem serum THC / Metabolites LC-MS/MS ND * Amphetamine Benzoylecgonine LC-MS/MS Cotinine Venlafaxine LC-MS/MS Ecgonine-methylester O-desmethylvenlafaxine LC-MS/MS Tramadol Nicotine LC-MS/MS (not in DB) Caffeine LC-MS/MS Methadone LC-MS/MS EDDP LC-MS/MS GS 25 U Post mortem urine Cotinine LC-MS/MS Amphetamine Nicotine LC-MS/MS (not in DB) Carboxy-THC** Tramadol Caffeine LC-MS/MS EDDP** Theobromine LC-MS/MS (not in DB) Methadone** Venlafaxine LC-MS/MS Desmethylvenlafaxine LC-MS/MS Benzoylecgonine LC-MS/MS Ecgonine methyl ester LC-MS/MS

11 Table 7: continued Case # Compound Result type Detected Additional False (DI concept) Findings Positives GS 548 Se Post mortem serum Promethazine Toxtyper Cotinine NONE Fentanyl Toxtyper Caffeine Diazepam Toxtyper Olanzapine Methadone Toxtyper Nordazepam Toxtyper Mirtazapine Toxtyper Methadone 32 ng/ml LC-MS/MS EDDP 1 ng/ml LC-MS/MS Pregabalin 1.8 µg/ml LC-MS/MS ND* Promethazine 42 ng/ml LC-MS/MS Fentanyl 74 ng/ml LC-MS/MS Norfentanyl 1 ng/ml LC-MS/MS Phenothiazine 27 ng/ml LC-MS/MS Mirtazapine 48 ng/ml LC-MS/MS Diazepam LC-MS/MS Nordazepam LC-MS/MS Oxazepam LC-MS/MS Temazepam LC-MS/MS Lorazepam LC-MS/MS (not in DB) GS 548 U Post mortem urine EDDP Toxtyper Norfentanyl NONE Methadone Toxtyper Fentanyl Toxtyper Mirtazapine Toxtyper Nicotine Toxtyper (not in DB) Mirtazapine GC-MS Promethazine GC-MS Pregabalin GC-MS Caffeine GC-MS Methadone GC-MS EDDP GC-MS Nicotine GC-MS (not in DB) Cotinine GC-MS Diazepam GC-MS Nordazepam GC-MS Oxazepam GC-MS Temazepam GC-MS * ND = Not Detected, analyte shows low extraction yield with chlorobutane ** Reported for serum

12 Bruker Daltonics is continually improving its products and reserves the right to change specifications without notice. Bruker Daltonics 5-215, LCMS-16, Discussion for Authentic Samples Again applying the diagnostic ion concept to the data for all authentic case samples excellent agreement was found with findings from routine analysis, i.e. UPLC QTOF [5], GC-MS [6], LC-MS/MS [7] and Toxtyper [4], (see Tables 6 & 7). False positive findings were again completely removed, with the only exception again being tramadol in presence of o-desmethylvenlafaxine. Reliable detection was achieved for compounds included in the database at low and high levels. A few additional findings were also observed compared to the routine methods. Many of them were commonly found compounds (e.g. cotinine, caffeine) or plausible trace findings (e.g. cocaethylene for a reported cocaine finding). Conclusion The forensic toxicology screening workflow and associated hardware has been shown to work reproducibly for serum and urine samples at three different sites. The efficacy of the diagnostic ion concept using bbcid qualifier ions has proven to be a very powerful tool to eliminate false positive findings. Furthermore, the workflow provides a sensitive screening method exploiting a low detection threshold with optimum retention time windows to avoid false negatives. The ability to add new compounds to the accurate mass bbcid and TOF-MS database, without changing the acquisition method, provides considerable scope to easily extend the screening method to include additional compounds of forensic toxicological relevance as future needs arise. Further work will center on applying the diagnostic ion concept to a larger forensic toxicology bbcid database to enable comprehensive, in-depth forensic investigations to be realized. References [1] 214 Global Synthetic Drugs Assessment: Amphetaminetype stimulants and new psychoactive substances, UNODC [2] S. Ojanperä, A. Pelander, M. Pelzing, I. Krebs, E. Vuori, I. Ojanperä; Isotopic pattern and accurate mass determination in urine drug screening by liquid chromatography/time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 26 2: [3] M. Sundström, A. Pelander, V. Angerer, M. Hutter, S. Kneisel, I. Ojanperä, A high-sensitivity ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method for screening synthetic cannabinoids and other drugs of abuse in urine. Anal Bioanal Chem. 213 Aug 18. [Epub ahead of print] DOI 1.17/s [4] L.M. Huppertz, S. Vogt, J. Kempf, Ein automatisiertes MSnbasiertes Screening Verfahren fü r die klinische und forensische Toxikologie. Toxichem Krimtech 213, Band 8 (Special Issue) Seiten [5] A. de Castro, M. Gergov, P. Ostman, I. Ojanperä, A. Pelander, Combined drug screening and confirmation by liquid chromatography time-of-flight mass spectrometry with reverse database search. Anal Bioanal Chem. 212 May; 43(5): [6] H.H. Maurer, K. Pfleger, A.A. Weber, Mass Spectral Library of Drugs, Poisons, Pesticides, Pollutants and Their Metabolites 211, Wiley-VCH, Weinheim ISBN [7] S. Dresen, N. Ferreirós, H. Gnann H, R. Zimmermann, W. Weinmann, Detection and identification of 7 drugs by multitarget screening with a 32 Q TRAP LC-MS/MS system and library searching. Anal Bioanal Chem. 21 Apr; 396(7): For research use only. Not for use in diagnostic procedures. Bruker Daltonik GmbH Bremen Germany Phone +49 () Fax +49 () Bruker Daltonics Inc. Billerica, MA USA Phone +1 (978) Fax +1 (978) ms.sales.bdal@bruker.com -