7 Appendix. 7.1 Performance Control Samples. Table 7-1 Compounds of the PCS with structure and pk a values. 7 Appendix 112. Literature.

7 Appendix 112 7 Appendix 7.1 Performance Control Samples Table 7-1 Compounds of the PCS with structure and pk a values ame Concentration (µg/ml) Chemical structures pk a Literature Codeine 1. 8.2 [97] H 2-Ethyliden-1,5- dimethyl-3,3-diphenylpyrrolidine (EDDP) 1. 9.6 [97] 3,4-Methylene-dioxyamphetamine (MDA) 1. H 2 9.7 [8] Morphine 1. H 8., 1. [97, 15] H Scopolamine 1. H H 7.6 [15] eostigmine bromide () 5. + Br - -

7 Appendix 113 Table 7-2 Compounds of PCS-BDP with structure and pk a values ame Concentration (µg/ml) Chemical structure pk a Literature Bromazepam 1. 2.5, 5.2, 11.8 [15] Demoxepam 1. 4.5, 1.6 [8] ordiazepam 1. 3.5, 12. [8] xazepam 1. 1.7, 11.6 [8] Temazepam 1. 1.6 [8] MPPH () 5. ~ 8. [15] H H CH 3 Table 7-3 Compounds of PCS-BARB with structure and pk a values ame Concentration (µg/ml) Chemical structure pk a Literature Cyclobarbital 1. 7.6 [8] Crotylbarbital 1. 7.7 [15] Methohexital 1. H C 2 H 5 H 8.3 [8] Phenobarbital 1. 7.4 [8] Pentobarbital 1. H 8. [8] C 2 H 5 C 3 H 7 H H MPPH () 1. ~ 8 [15] H CH 3

7 Appendix 114 Table 7-4 Compounds of PCS-PA with structure and pk a values ame Concentration (mg/ml) Dipyridamol.1 Chemical structure pk a Literature H H 6.4 [8] H Diazepam.1 H 3.3 [8] Cl H MPPH ().1 ~ 8. [15] H CH 3

7 Appendix 115 7.2 Remedi TM -HS Fig. 7-1 Remedi TM -HS system [146] Fig. 7-2 Circuit diagram of the Remedi TM -HS system, V: valve, C1: purification column, C2: extraction column, C3 and C4: analytical columns [55]

7 Appendix 116 7.3 HPLC Equipment Reference System Auto sampler (SIL-6B) DAD system (SPD-1 AVP) UV detector (SPD 1 AVP) ven (CT-6A) Shimadzu Class VP TM software System controller (SCL-6B) Communication module (CBM 1A) Two pumps (LC-9A) Monitor (L731 TD) UV spectra of toxic compounds [22], Class VP TM files Degaser (DG 131) Computer Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany Shimadzu, Duisburg, Germany VDS ptilab, Berlin, Germany Peacock Tiara

7 Appendix 117 7.4 Libraries Library of the screening method for basic compounds in urine, status 1/7 Substance Retention Relative λ max (nm) time (min) retention time 6-AM 23.226.6 28.7/284.37 Aconitine 19.57.51 195.75/231.79/273.13 Alfentanil 25.744.68 323.94 Alimemazine 27.157.7 193.14/252.12/31.17 Alprenolol 19.164.49 195.97/27.23 Ambroxol 27.11.72 29.84/245.86/39.88 Amfetaminil 2.779.54 193.14/257.16 7-Aminoflunitrazepam 18.827.54 242.65 Aminosuxethimide 17.581.46 193.14/236.66 Amisulpride 32.765.87 225.67/279.78 Amisulpride-Met.1 26.22.7 225.64/278.66 Amitriptyline 24.98.67 23.14/238.57 Amitriptylinoxide 21.461.58 23.63/238.39 Amlodipine 18.18.47 194.3/238.1/362.37 Amphetamine 21.98.56 194.3/24.91/256.95 Atenolol 2.655.54 194.3/224.79/273.31 Atomoxetine 19.7.52 195.32/269.67 Atracurium 26.854.72.51/23.66/28.28 Atracurium-Met. 22.5.6.12/231.87/28.36 Atropine 23.827.62 257.18 Benzatropine 23.886.62 194.3/258.29 BEC 14.144.36 194.3/231.65/273.29 Betaxolol 19.46.51 194.3/222.56/273.82 Biperidene 24.667.63 193.14/256.76 Bisnortilidine 19.11.49 193.14 Bisoprolol 2.682.55 195.78/224.62/271.99 Bufotenine 21.39.58 23.47/275.41 Bupivacaine 26.47.67 193.86/262.25 Buprenorphine 24.25.62 211.85/286.25 Buspirone 41.814 1.13 237.33/212.53/.49 Carvedilol 22.447.58 214.41/25.7 Cathinone 23.671.61 197.32/248.31 Celiprolol 22.383.58 232.81/194.99/327.8 Cetirizine 5.718 1.36 193.14/23.64 Chloramphenicol 17.746.46 197.18/27.4 Chlorphenetazine 28.643.74 252.5/193.14/33.56 Chlorpheniramine 23.983.64 194.9/251.42 Chlorphenoxamine 23.927.64 194.18/258.37 Chlorphentermine 19.992.53 195.66/219.74/265.31 Chlorpromazine 28.546.77 255.8/37.1 Chlorprotixene 29.896.81 229.9/27.14/268.32/325.64 Cicletanine 19.339.52 194.63/216.5/284.44 Cimetidine 22.226.59.7 Citalopram 23.66.61 193.49/238.68/283.78 Citalopram-Met. 1 19.319.5 193.23/238.22/283.69 Citalopram-Met.1 19.667.54 193.14/238.44/272.7/283.7 Clemastine 22.52.57 195./259.38 Clenbuterol 36.45.54 212.3 Clobutinol 24.285.62 195.74/221.15/266.9 Clomipramine 25.546.68 252.28 Clomipramine-Met. 1 22.835.63 195.9/25.32 Clomipramine-Met.2 22.26.61 193.14/249.17

7 Appendix 118 Substance Retention Relative λ max (nm) time (min) retention time Clonidine 25.94.7 198.62/27.94 Cocaine 28.19.71 195.6/232.1/274.9 Codeine 31.76.79 211.25/194.3/284.22 Cotinine 25.146.64 194.3/26.58 Cycloguanil 25.467.66 193.14/241.2 Cyproheptadine 25.843.67 224.12/194.3/289.63 Cytisine 34.281.94 195.92/34.58/232.23 Dimethoxy-bromomethamphetamine 19.193.49 199.39/234.21/285.6 Desacetyldiltiazem 25.484.66 194.83/236.25 Desalkyl-flurazepam 37.51 1.3 228.77/37.49 Desipramine 22.473.6 193.14/251.44 Desmethyltrimipramine 23.189.62 193.89/25.95 Dihydrocodeine 31.399.83 28.69/283.26 Dioxopromazine 29.969.78 225.61/193.14/264.18/29.27/326.49 Diphenhydramine 22.972.61 193.14/258.13 Diphenhydramine-Met. 1 17.189.56 193.14/258.2 Diphenylpyraline 21.265.58 194.95/258.16/298.74 Dopamine 18.216.49.1/285.9 Dothiepine 25.69.65 193.14/229.4/32.45 Doxapram 25.914.68 195./258.31 Doxepin 26.63.69 25./293.34 Doxycycline 2.163.5 194.3/267.77/347.5 Doxycycline-Met.1 18.73.47 194.3/268.4/214.28/347.78 Droperidol 25.959.67 23.16/245.26/229.13/277.39 Duloxetine 2.65.56 216.19/29.19 EDDP 36.36.92 194.3/235.44 Unidentified endogeneous peak 17.935.45 193.14/221.56/273.35 Unidentified endogeneous peak 19.86.52 219.51/196.88/277.35 Unidentified endogeneous peak following hydrolysis 32.24.84 24.43/24.55 Unidentified endogeneous peak following hydrolysis 12.617.33 193.14/257.92 Unidentified endogeneous peak following hydrolysis 2.728.54 193.14/25.3/259.74 Unidentified endogeneous peak following hydrolysis 18.48.48 198.84/222.46/278.81 Unidentified endogeneous peak following hydrolysis 18.975.5 195.53/282.84/313.23 Ephedrine 2.755.54 24.61/256.71 Ergotamine 22.452.6 193.14/317.41 Fencamfamine 22.477.57 194.3/27.13/258.58 Fenfluramine 19.388.53 193.14/26.5/262.43 Fentanyl 28.55.74 256.85/324.27 Fexofenadine 17.84.46 193.14/259.9 Flecainide 18..5 198.68/298.27 Fluoxetine 19.191.51 193.84/226.71/263.44 Flurazepam 39.62 1.8 193.27/228.87/36.92 Fluvoxamine 17.789.48 25.35 Galantamine 32.636.87 211.65/288.93 Gallopamil 2.667.55 21.45/276.68 Haloperidol 25.395.68 194.52/246.8 Heroin 23.381.6 24.23/279.1 Hydroxy-methoxyamphetamine 21.174.54 199.47/226.19/279.24 Hydrocodone 24.258.73 25.74/28.66 Hydromorphone 25.937.66 24.41/28.65

7 Appendix 119 Substance Retention Relative λ max (nm) time (min) retention time Hydroxyzine 33.792.86 193.14/23.7 Hyoscyamine 23.85.62 194.3/256.62 Imipramine 27.219.71 193.83/251.12 Ipratropiume 36.638.98 256.88/331.86 Ketamine 25.39.71 194.47/268.25 Ketamine-Met. 1 24.9.65 194.3/267. Ketamine-Met. 2 22.14.6 194.3/267.44 Ketamine-Met. 3 19.155.52 194.3/214.47/267.93 Ketotifen 3.358.79 23.45/298.12 Labetolol 2.797.54 25.71/193.14/32.58 Lamotrigine 2.87.54 28.13/264.67 Levofloxacine 33.573.88 294.28/226.3/193.14/325.65 Levofloxacine Met. 1 23.956.66 294.84/223.42/325.9 Lidocaine 25.536.67 193.94/262.48 Lidocaine-Met. 1 21.71.55 194.3/262.79 Lidocaine-Met. 2 19.166.5 194.3/262.83 Lisuride 34.12.87 193.14/225.36/239.88/312.1 LSD 35.259.94 232.1/312.6 LSD-Met. 1 33.15.88 225.66/312.14 LSD-Met. 2 29.56.78 232.65/315.7 LSD-Met. 3 28.635.76 225.32/312.38 Maprotiline 23.688.63 193.52/271.75/264.89 Methyl-1-(benzodioxol-5-yl)- butamine 21.55.53 199.57/234.4/285.25 MDA 21.444.54 199.28/233.96/284.87 Methylenedioxyamphet. 22.56.58 197.96/234.34/285.6 MDMA 22.67.57 199.45/233.95/285.5 Medazepam 31.243.89 194.23/253.42 Mefloquine 19.831.53 221.74/282.49/316.44 Melperone 31.11.83 196.18/246.9 Melperone-Met.1 24.6.67 196.69/245.42 Mepivacaine 27.189.73 193.14/262.37 Mescaline 21.81.55 23.98/268.4 Mesoridazine 4.574 1.1 261.1/238.53/37.58 Mesoridazine-Met. 1 3.98.85.85/262.9/238.62/311.76 Metaclazepam 29.115.79 194.52/252.18 Metamphetamine 23.466.59 194.3/25.31/256.99 Methadone 25.19.65 194.3/259.3/289.5 4-Methoxyamphetamine 19.358.53 196.42/223.34/274.2 4-Methoxymetamphetamine 21.419.59 196.21/223.6/274.27 Methylphenidate 22.757.6 193.14/256.84 Metoclopramide 32.64.87 213.8/274.5/39.4 Metoclopramide-Met. 27.243.71 214.11/271.77/37.49 Metoprolol 21.47.57 195.48/222.39/273.79 Metoprolol-Met. 1 19.175.54 196.2/223.27/272.1 Mexiletine 2.238.52 198.1/261.52 Midazolam 29.92.83 218.32 Moclobemide 27.92.71 197.96/238.77 Morphine 25.74.65 29.38/194.3/284.99 Moxonidine 25.5.68 196.46/231.9/325.5 aloxone 22.366.6 23.93 -Desmethyldiphenhydramine 19.599.66 193.14 -Desmethyldoxepin 23.291.62 24.86/293.15 efazodone 23.344.62 193.14/29.4/248.46 eostigmine bromide () 39.468 1. 26.14 icotine-met. 25.888.66 23.8/258.6

7 Appendix 12 Substance Retention Relative λ max (nm) time (min) retention time oramidopyrine 2.77.59 194.3/26.21/241.55 oramidopyrine-met. 2.1.57 194.3/26.19/241.64 orazepam 18.977.53 193.36/235.43 orbuprenorphine 23.183.6 211.64/286.52 orcitalopram 21.6.55 193.63/238.62/283.77/318.16 orclomipramine 22.689.61 193.14/252.66 orcocaine 2.368.57 195.24/231.71/274.51 orcodeine 25.349.65 21.66/194.8/284.65 orephedrine 19.83.5 193.14/25.14/256.4 orfentanyl 24.299.63 256.5/324.15 ormaprotiline 21.52.57 193.65/271.75/264.88 ormethadone 2.985.57 193.14/259.56/292.37 ormethadone 21.659.56 194.3/259.36/292.32 ormorphine 2.656.56 29.42/194.29/285.49 orpseudoephedrine 19.17.49 193.14/256.4 orsertraline 23.829.7 194.8/272.97/265.63 orthioridazin-2-sulfoxide 3.98.85.85/262.9/238.62/311.76 ortilidine 21.12.55 ortrimipramine 19.497.6 194.46/249.14 ortriptyline 22.6.59 193.14/238.17 orvenlafaxine 21.557.57 195.8/224.6/275.4 orverapamil 2.886.56.67/229.74/278.4 oscapine 26.148.7 212.48/312.15 oxiptiline 23.658.61 193.14/248.93 floxacine 32.138.85 294.34/226.7/193.14/325.71 rciprenaline 16.589.43 198.44/277.79 xybutynine 19.15.48 193.14/256.85 xycodone 28.896.75 25.52/281.19 xymotphone 22.78.58 24.27/281.52 Papaverine 35.927.96 251.13/199.83/39.1/286.63 Paroxetine 21.265.57 293.52/234.2 Penbutolol 19.123.49 196.63/215.65/27.57 Pentamidine 17.412.46 196.16/258.96 Pentazocine 22.445.6 197.27/278.88 Perazine-Met. 4 23.914.62 194.3/248.91/34. Perazine-Met. 1 38.34 1. 194.3/233.22/21.23/267.41/291.79 Perazine-Met. 2 32.198.84 233.18/194.3/267.9/292.47/335.92 Perazine-Met. 3 26.422.69 225.53/194.3/264.48/29.7/326.99 Perazine-Met. 5 21.245.55 194.3/248.98/33.11 Perazine-Met. 6 19.74.52 194.3/248.99/31.92 Periciazine 29.317.74 268.74/193.14/231.85 Pethidine 24.486.63 193.11 Pethidine-Met. 1 21.853.55 194.3/254.92/38.46 Pethidine-Met. 2 2..51 194.3/256.57 Pethidine-Met.3 19.314.49 194.3 Phertarmine 21.561.57 193.14/258.26 Pholedrine 19.522.49 193.14/222.72/275.21 Physostigmine 26.126.7 23.13/246.2/32.51 Pirenzepine 54.79 1.49 199.71/281.6 Pizotifene 26.837.95 193.14 p-methoxyamphetamine 21.619.55 194.3/223.5/273.9 p-methoxymetamphetamine 23.93.61 194.3/223.73/274.3 Pridinol 22.941.63.88/257.71 Procyclidine 24.913.66 193.14/256.74 Proguanil 33.353.91 196.61/256.74/231.69 Prolinthan 27.753.74 193.14/257.52

7 Appendix 121 Substance Retention Relative λ max (nm) time (min) retention time Prolocaine 2.166.53 194.64/226.16 Promazin-S-oxide 34.14.92 231.46/271.38/298.1/341.52 Promazin-S-oxide-Met. 1 28.763.73 194.3/231.64/272.7/298.36/342.52 Propafenone 2.23.51 193.14/28.6/248.22/33.77 Propranolol 21.264.56 212.77/29.7 Pseudoephedrien 19.745.5 194.3/25.38/256.67 Psilocin 21.427.56 22.46/266.5 Remifentanil 24.392.64 193.14/257.64 Rifabutine 19.471.51 28.36/277.9/236.89/316.19/355.2 Ritodrine 15.32.41 197.62/221.94/274.52 Ropivacaine 26.14.69 193.14/262.27 Scopolamine 22.17.57 257.9 Sertindol 28.26.73 193.14/224.4/255.54/299.46 Sertraline 26.27.63 194.99/265.96 Sildenafil 25.22.68 223.21/213.49/193.84/292.85 Sildenafil-Met. 23.821.98 223.13/213.67/194.38/292.24 Sufentanil 25.858.69 193.14/226.6 Sulpiride 31.176.83 212.47/291.89 Talinolol 19.648.51 195.38/241.81/284.58 Terfenadine 18.428.49 193.14 Tetrazepam 32.752.86 237.63/24.49/28.43 Thebaine 3.289.43 23.93/284.57 Thiabendazole 28.585.76 195.22/31.63/243.53 Thioridazine 3.162.82 262.54/229.23/31.4 Thioridazin-2,5-disulfoxide 47.387 1.3 193.14/233.97/217.88/31.99/346.61 Thoncylamine 43.799 1.16 194.58/24.71/28.29/37.42 Tiapride 31.44.79 212.38/287.71 Tilidine 28.182.71 194.3/257.21 Tilidine-Met. 1 18.566.49 194.3/256.41 Tilidine-Met. 2 18.86.47 194.3/258.4 Tilidine-Met. 3 17.645.46 194.3/258.64 Timolol 21.858.56 296.64/193.14 Tizanidine 29.381.79 197.75/227.11/318.67 Tocainide 21.39.58 193.61/263.12 Tramadol 22.569.58 196.64/215.5/271.37 Tramadol-Met. 1 2.622.57 197.4/271.42 Tramadol-Met. 2 19.855.55 196.8/272.57 Tramadol-Met. 3 19.83.52 197.23/272.45/328.63 Tranylcypromine 2.78.53 195.12/262.32 Trazodone 31.235.83 211.2/248.74/314.63 Trichlorphone 25.31.67.93/261.4 Trifluperidole 21.158.53 193.14/246.3 Triflupromazine-Met. (S-oxide) 27.817.76 233.49/193.14/216./272.94/.77 Triflupromazine-Met. (S-oxide) 24.747.67 233.34/215.94/193.14/273.14/31.18 Triflurpromazine 23.21.62 256.76/193.14/36.37 Trihexyphenidyl 25.466.66 193.14/256.59 Trimethoprime 22.728.59 23.94/27.41 Trimetoprim-Met. 1 2.114.56 22.82/273.74 Trimetoprim-Met. 2 19.36.54 25.8/269.21 Trimipramine 26.357.68 193.85/25.49 Trimipramine-Met. 1 18.267.56 195.17/248.69 Triperidene 29.9.75 193.14/256.87 Urapidil 37.353 1.15 23.62/267.86/237.23 Urapidil-Met. 1 28.896.95 195.84/267.81 Verapamil-Met.2 18.698.5.18/228.55/278.52 Venlafaxine 25.485.66 196.52/225.63/274.17/329.26

7 Appendix 122 Substance Retention Relative λ max (nm) time (min) retention time Venlafaxin-Met. 1 2.291.58 196.34/224.52/275.19 Venlafaxin-Met. 2 18.536.53 195.75/223.9/275.2 Venlafaxin-Met. 3 17.574.5 194.76/223.85/275.26 Verapamil 22.894.59.45/229.95/278.5 Verapamil-Met.1 19.843.53 199.12/23./277.63 Verapamil-Met.3 18.38.49.89/229.87/277.74 Verapamil-Met.4 18.137.48.68/229.9/278.65 Veratrine 19.76.51 219.52/261.92/292.9 Xylometazoline 23.628.57 197.2/262.31 Yohimbine 31.561.82 219.43/27.71/349.87 Ziprasidone-Met. 35.552.94 28.46/314.53 Zolpidem 42.872 1.1 26.86/237.9/295.49 Zolpidem-Met. 27.784.72 25.22/297.85 Zopiclon-Met. 1 25.889.71 193.14/34.3 Zopiclon-Met. 2 19.819.64 193.14/34.12/214.55

7 Appendix 123 Library of the Screening Method for eutral, Weakly Acidic and Weakly Basic Compounds in Urine, Status 1/7 Substance Retention time Relative λ max (nm) (min) retention time Alprazolam 4.284 1.35 194.3/221.29 Amobarbital 19.59.7 194.3 Bamipine 22.37.79 194.3/25.93/297.37 Brallobarbital 16.72.6 194.3 Bromazepam 17.99.6 233.77/194.3 Brotizolam 48.75 1.63 194.3/24.92 Butalbital 16.641.59 194.3 Carbamazepine 22.193.79 194.3/21.95/284.4 Carbromal 19.66.68 195.65 Chinine 11.157.4 27.18/245.49/341.4/318.23 Chlordiazepoxide 13.99.5 243.95/194.3/22.85/37.7 Chlorphenamine 13.843.48 194.3/221.75/262.75 Clobazam 35.974 1.28 229.67/194.3/288.8 Clomethiazole 19.4.69 251.26/194.3 Clonazepam 29.694 1.4 194.3/39.49 Clozapine 13.487.48 23.29/24.27 Colchicine 2.744.74 243.69/197.99/351.75 Crotylbarbital 23.682.77 194.3 Cyclicine 19.859.71 194.3/224.57/257.46 Cyclobarbital 16.67.54 194.3 Dantrolene 24.9.86 194.3/39.27/224.14 Demoxepam 19.846.69 236.24/194.3/35.98 Desalkylflurazepam 34.581 1.12 229.14/194.3/31.63 Diazepam 4.394 1.37 194.3/232.37/279.41/36.44 Diltiazem 22.691.81 194.3/236.84 Dimenhydrinat 2.354.73 194.3/257.93/299.61 Flumazenil 18.353.66 21.37/243.94/354.62 Flurazepam 21.268.76 194.3/228.65/37.79 Glisoxepide 32.378 1.15 194.3/229.36 Glutethimide 22.54.81 194.3/255.47/288.77 Heptabarbital 24.344.87 194.3 Hexobarbital 19.643.7 194.3 1-Hydroxymidazolam 17.492.61 194.3/218.12/345. 4-Hydroxymidazolam 18.544.58 194.3/218.29 Leflunomide 31.798 1.14 291.4/246.95/.46 Loprazolam 18.515.66 194.3/328.45/235.77 Lorazepam 25.824.9 194.3/229.14/316.38 Lormetazepam 37.286 1.26 194.3/23.58/315.74 Mesoridazine 22.316.8 26.96/194.3/238.21/37.79 Mesuximide 21.632.77 194.3 Methohexital 35.59 1.12 194.3/22.1 Methylphenobarbital 21.219.76 194.3 Midazolam 21.31.68 194.3/218.19 Mirtazepin 12.83.43 194.3/313.66/251.2 - Desmethylchlordiazepoxide 14.233.48 194.3/245.21/299.23 itrazepam 23.879.83 194.3/216.82/26.82 orclobazam 27.73.9 227.42/194.3/289.81 ordiazepam 25.8.87 194.3/232./28.61 pipramol 14.38.51 194.3/253.94/215.5 xazepam 23.363.81 228.86/194.3/313.54 xcarbazepine 17.74.63 194.3/255.9/35.43

7 Appendix 124 Substance Retention time Relative λ max (nm) (min) retention time Pentobarbital 2.256.66 194.3 Phenmediphame 23.942.86 22.58/235.48/272.56 Phenobarbital 15.451.5 194.3 Quinapril 25.523.91 194.3/26.2 Ramipril 19.416.69 194.3/257.56 Risperidone 14.992.53 195.65/236.67/274.3 Secobarbital 21.8.78 194.3 Secubutabarbital 15.368.55 194.3 Temazepam 33.841 1.14 197.22/23.46/31.18 Tetrazepam 16.686.54 234.46/199.31/28.81/352.47 Thonzylamine 15.494.55 194.3/24.44/28.32/37.27 Tiagabine 36.498 1.29 194.3/257.62 Trapidil 13.961.49 32.11/22.17/198.62 Triflurpromazine 17.97.64 233.47/194.3/215.46/272.76/.27 Zopiclone 22.382.8 194.3/32.85

7 Appendix 125 7.5 Stability Investigations Table 7-5 Stability investigations on PCS 2 stored at room temperature Analyte Recovery (day -28), % (Mean, ± SD) Recovery range, % RSD, % Codeine 97 ± 3.8 91-3.8 EDDP 85 ± 4.8 78-91 5.5 MDA 97 ± 9.4 77-9.7 Morphine 96± 1.3 84-18 1.5 Scopolamine 4 ± 33.1 14-94 85.8 97 ± 8.4 88-13 7.4 Table 7-6 Stability investigations on PCS 2 stored at 5-8 C (fridge) Analyte Recovery (day -28), % (Mean, ± SD) Recovery range, % RSD, % Codeine 98 ± 8.6 97-16 8.3 EDDP 99 ± 4.8 78-91 5.5 MDA 95 ± 4.1 89-99 4.4 Morphine 98 ± 7. 87-12 7.1 Scopolamine 64 ± 22.2 43-95 34.9 99 ± 8.2 98-14 8.3 Table 7-7 Stability investigations on PCS 2 stored at -15 C (freezer) Analyte Recovery (day -28), % (Mean, ± SD) Recovery range, % RSD, % Codeine 99 ± 5.5 94-16 5.4 EDDP 12 ± 5.5 98-14 5.3 MDA 98 ± 5.2 94-13 5.2 Morphine 95 ± 5.8 9-12 6.1 Scopolamine 93 ± 2.5 89-96 2.7 14 ± 7.6 92-111 6.9 Table 7-8 Stability investigations on PCS 1 stored at 5-8 C (fridge) Analyte Recovery (day -28), % (Mean, ± SD) Recovery range, % RSD, % Codeine 99 ± 1.1 97-11 1.1 EDDP ± 1.4 98-12 1.4 MDA 98 ± 1.1 96-11 1.1 Morphine 98 ± 6. 89-13 6.1 Scopolamine 95 ± 8.8 83-12 9.3 98 ± 9.1 85-19 9.4

7 Appendix 126 Table 7-9 Stability investigations on PCS 1 stored at -18 ± 3 C (freezer) Analyte Recovery (day -28), % (Mean, ± SD) Recovery range, % RSD, % Codeine 98 ± 2.3 94-2.3 EDDP 98 ± 1.2 98-12 1.2 MDA 99 ± 1.2 97-.9 Morphine 99 ± 6. 9-12 2.2 Scopolamine 98 ± 4.6 9-12 4.7 99 ± 1.5 97-11 1.6 Table 7-1 Stability investigations on the new PCS 1* stored at -18 ± 3 C (freezer) Analyte Recovery (day -67), % (Mean, ± SD) Recovery range, % RSD, % 6-AM 96 ± 2.2 91-13 2.3 Codeine 99 ± 8.6 81-12 8.6 EDDP 99 ± 4.1 96-13 4.1 MDA 98 ± 5.1 97-5.2 Morphine 98 ± 6.4 9-13 6.5 Tilidine 96 ± 4.6 91-14 4.8 95 ± 9.7 87-14 1.2 Table 7-11 Stability investigations on the PCS-BDP stored at -18 ± 3 C (freezer) Analyte Recovery (day -67), % (Mean, ± SD) Recovery range, % RSD, % Bromazepam 14 ± 1.4 94-116 1. Demoxepam 12 ± 4.9 95-15 4.8 ordiazepam 97 ± 11.2 96-14 11.4 xazepam ± 3.1 85-16 3. Temazepam 95 ± 9.4 84-119 9.8 MPPH () 15 ± 15. 87-15 14.3

7 Appendix 127 7.6 Validation Data Table 7-12 Recovery, RSD, LLD and linearity data of the screening method for basic compounds in urine, PCS 2 Analyte Recovery (mean level 1-3) (%) ± SD RSD (recovery) (%) RSD (RRT) (%) LLD (µg/ml) Linearity Range (µg/ml) R 2 Codeine 9.6 ± 1.2 1.3.2.1.2 15..9997 EDDP 94.3 ± 1.8 1.9.2.1.2 15..9999 MDA 96.9 ±.7.8.2.1.2 5..9926 Morphine 83.2 ± 2.9 3.5.2.1.2 15..9947 Scopolamine 78.7 ± 4.9 7.2.2.2.25 15..9977 72.7 ± 2.4 3.3.2.2.25 15..9949 Table 7-13 Recovery, RSD, LLD and linearity data of the screening method for neutral, weakly acidic and weakly basic compounds in urine, PCS-BDP 2 Analyte Recovery (X Level 1-3) (%) ± x (SD) RSD (Recovery) (%) RSD (RRT) (%) LLD (µg/ml) Linearity Range (µg/ml) R 2 Bromazepam 95. ± 8. 6.5.1.4.5-1..9993 Demoxepam 63. ± 2.6 4.1.2.3.5-1..9992 ordiazepam 95.7 ± 9. 8.4.1.1.1-2..999 xazepam 93.7 ± 1.7 1.8.3.3.5-1..9997 Temazepam 93.7 ± 6.5 6.1.5.3.5-1..997 MPPH () 43.7 ± 1.3 3..1.3.5-2..9993

7 Appendix 128 Table 7-14 Recovery, RSD, LLD and linearity data of the screening method for neutral, weakly acidic and weakly basic compounds in urine, PCS-BARB 2 Analyte Recovery (X Level 1-3) (%) ± x(sd) RSD (Recovery) (%) RSD (RRT) (%) LLD (µg/ml) Linearity Range (µg/ml) R 2 Cyclobarbital 1.7 ±.7 6.7.1 1. 5.-4..989 Crotylbarbital 13. ± 1.5 11.3.1 1. 1.-2..987 Methohexital 71.9 ± 1.1 1.5.2.1.1-2..9995 Phenobarbital 4.6 ±.3 6..1 1. - - Pentobarbital 62.4 ± 2. 3.2.1.1.1-2..995 MPPH () 43.7 ± 1.3 3..1.3.5-2..9993

7 Appendix 129 7.7 Example Chromatograms STA: Antidepressants 4 mau 25nm,4nm (1.) Amitriptyline-Metabolites ortriptyline Amitriptyline 1 2 3 min STA: Antidepressants mau 25nm,4nm (1.) Citalopram- Metabolites orcitalopram Citalopram 1 2 3 min STA: Antidepressants 4 mau 25nm,4nm (1.) Citalopram Trimipramine- Metabolite Trimipramine 1 2 3 min

7 Appendix 13 STA: Antidepressants 4 mau 25nm,4nm (1.) Amisulpride Amisulpride- Metabolite 1 2 3 min STA: euroleptics 35 mau 25nm,4nm (1.) 25 Promethazine-Metabolites 15 5 1 2 3 min STA: Analgetics mau 25nm,4nm (1.) Tramadol- Metabolites Amisulpride Amisulpride- Metabolite 1 2 3 min

7 Appendix 131 STA: Antihistamines mau 25nm,4nm (1.) 35 25 Diphenhydramine- Metabolites Diphenhydramine 15 5 1 2 3 min STA: Sleeping medication 4 mau 25nm,4nm (1.) Zolpidem- Metabolite 1 2 3 min STA: thers 4 mau 25nm,4nm (1.) Amitriptyline- Metabolites Ciprofloxacine Ambroxol 1 2 3 min

7 Appendix 132 DA: piates mau 25nm,4nm (1.) 35 25 6-Acetylmorphine ormorphine Morphine 15 5 Codeine 1 2 3 min DA: Amphetamines 35 mau 25nm,4nm (1.) Amphetamine MDMA 25 15 MDA 5 1 2 3 min DA: Cocaine (BEC method) 35 25 15 mau 25nm,4nm (1.) BEC 5 1 2 3 min

7 Appendix 133 DA: Methadone substitution 4 mau 25nm,4nm (1.) 35 25 Methadone EDDP 15 -Desmethyldoxepine 5 1 2 3 min DA: pioid abuse 4 mau 25nm,4nm (1.) Bisnortilidine ortilidine 1 2 3 min DA: pioid abuse mau 25nm,4nm (1.) Tramadol- Metabolites EDDP Tramadol 1 2 3 min

7 Appendix 134 7.8 Evaluation of Benzodiazepine Positive Samples Immunological result analysed by CEDIA with Detected benzodiazepines deglucuronidation reagent* 1774 xazepam, Temazepam 655 Temazepam 93-1867 Hydroxymidazolam 1654 xazepam, Temazepam 1654 verlapped spectra 169 xazepam, Temazepam 16 xazepam, Temazepam 747 Temazepam 1378 verlapped spectra 1819 xazepam 1524 Demoxepam, xazepam Demoxepam, xazepam, ordiazepam, 1918 Temazepam 1967 xazepam, Temazepam 1813 xazepam, Temazepam 1392 verlapped spectra 1998 xazepam, Temazepam 1375 xazepam, Temazepam 287-297 - 234 xazepam, Temazepam 244-285 - 291 xazepam, Temazepam 38-314 - 52 Lorazepam, xazepam, Temazepam 526-53 - 649-794 - 83-937 - 143 xazepam, Temazepam 151-1363 Flurazepam 1378 Temazepam 144 Temazepam 148 xazepam, Temazepam 1521 Hydroxymidazolam 164 Temazepam 164 xazepam 178 xazepam, Temazepam 1721 xazepam, Temazepam 1751 xazepam, Temazepam 181 Temazepam 1857 xazepam, ordiazepam, Temazepam 1861 xazepam, Temazepam 1876 xazepam, Temazepam 1927 xazepam, Temazepam 1928 xazepam, Temazepam 1929 xazepam, ordiazepam, Temazepam 194 xazepam, Temazepam 1997 xazepam, Temazepam

7 Appendix 135 Immunological result analysed by CEDIA with Detected benzodiazepines deglucuronidation reagent* 2182 xazepam, Temazepam 2258 xazepam, Temazepam 2297 xazepam, ordiazepam, Temazepam 2312 ordiazepam, Temazepam 2338 xazepam, Temazepam 2345 xazepam, Temazepam 2362 Temazepam 244 xazepam, Temazepam 2451 xazepam, ordiazepam, Temazepam 249 xazepam, Temazepam 255 xazepam, ordiazepam, Temazepam 2521 xazepam, Temazepam 2121 Temazepam 2157 Tetrazepam 234 xazepam, Temazepam 244 - *investigated within DA confirmation screening, creatinine ranged from.6-3.8 g/l

7 Appendix 136 7.9 egative List Compound Compound Allopurinol elfinavir Amantidine icotine Amodiaquine ifluminic acid Aripiprazol ilvadipine Atovaquone imodipine Bromocryptine methoat Caffeine Paracetamol Candesartan Perazine Cantharidine Pipamperone Ceftriaxone Pregabaline Cidofovir Propylthiouracil Cisapride Salicylic acid Clopenthixol Sulfadiazine Delavirdine Sultiam Diazoxid Theophylline Dimethoat Zidovudine Doxylamine Ziprasidon Enalapril Zotepin Ethenzamide Zuclopentixol Felbamat Felodipine Fenoterol Ganciclovir Gliborunide Glipizid Gliquidone Hydroxychloroquine Ibuprofen Indinavir Iomperol Itraconazol Lamivudine Lisinopril Lonazelac Loperamide Loratadine Mebendazol Memantine Meprobamat Mesoridazine Metronidazol aproxene

7 Appendix 137 7.1 Comparison of Column Shelf-Lives: Developed System versus Remedi TM -HS Developed system Remedi TM -HS Column type Shelf-life Column type Shelf-life C18 (Pre-(guard)cartridge 5 injections Purification cartridge 25 injections* Extraction column injections Extraction cartridge 25 injections* SCX (Pre-(guard)cartridge injections Separation cartridge 1 25 injections* Analytical columns 5- injections per column Separation cartridge 2 25 injections* Saturator cartridge Filter 25 injections* 25 injections** * guaranteed shelf-life by manufacturer ** exchanged together with the saturator cartridge