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Methamphetamine SUPPORTING INFORMATION FOR: Reflection of socio-economic changes in wastewater: licit and illicit drug use patterns Νikolaos S. Τhomaidis1,*, Pablo Gago-Ferrero1, Christoph Ort2, Niki C. Maragou1, 1 1 1 Nikiforos A. Alygizakis , Viola L. Borova , Marilena Dasenaki 1 Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece 2 Eawag, Swiss Federal Institute of Aquatic Science and Technology, Überlandstrasse 133, CH-8600 Dübendorf, Switzerland Pages: 61 Tables: 13 Figures: 3 *Corresponding author: Tel: +30 210 7274317 Fax: +30 210 7274750 E-mail: [email protected] For Submission to: Environmental Science & Technology S1 CONTENTS SI-1: Detailed substance information……………………………………………………………………………… S3 SI-2: Analytical method………………………………………………………………………………………………….. S9 SI-3: Pharmacokinetics and other relevant data used for back-calculated use of the selected substances……………………………………………………………………………………………………… S15 SI-4: Concentration values and loads of the target compounds in the analyzed influent wastewaters………………………………………………………………………………………………………………… S23 SI-5: Greek socio-economic indicators from 2010 to 2014……………………………………………. S58 S2 SI-1: Detailed substance information All drug standards were of high purity grade (>90%) and were purchased from Sigma-Aldrich (Athens, Greece) except sulfadoxine (SDX) and sulfaclozine (SClZ), which were donated by the National Laboratory of Residue Analysis of Food of Animal Origin of the Hellenic Ministry of Rural Development and Food. Regarding psychotropic drugs and illicit drugs and their metabolites, all target analytes were of high purity (˃ 98%). Solutions or solids were purchased from LGC Promochem (Molsheim, France), except topiramate and lamotrigine, which were obtained from Glenmark (Mahwah, NJ, USA) and Sigma Aldrich Chemie GmbH (Steinheim, Germany), respectively. Acetonitrile (ACN) and methanol (MeOH) LC–MS grade were purchased from Merck (Darmstadt, Germany) as well as hydrochloric acid (37%). Formic acid (FA) 99% was purchased from Fluka (Buchs, Switzerland). Ammonia 25% was purchased from Panreac (Barcelona, Spain) and ammonium formate from Fluka (Buchs, Switzerland). Distilled water was provided by a MilliQ purification apparatus (Millipore Direct-Q UV, Bedford, MA, USA). Strata-X cartridges (200 mg / 6 mL) and RC syringe filters (4 mm diameter, 0.2 μm pore size) were provided from Phenomenex (Torrance, CA, USA), while the glass fiber filters used (GFF, pore size 0.7 μm) in wastewater filtration were obtained from Millipore (Cork, Ireland). Individual stock solutions were prepared in either acetone or MeOH, at concentrations varying between 10 mgL-1 and 1250 mgL-1. Only penicillins, cephalosporines, and macrolides were dissolved in MilliQ-water. In quinolone standard solutions, 50 μL of formic acid were added to enhance solubility. Stock solutions of each compound were obtained and stored at −20 °C. A multi component solution of all the compounds was obtained by diluting the stock solutions in MeOH to a final concentration of 1 μgmL-1 and was also stored at −20 °C. From this multi-analyte solution all working solutions and calibration standards were prepared by gradient dilution in concentrations varying from 1 μgmL-1 to 1 ngmL-1. Infusion solutions of individual standards and internal standards (IS) were prepared at concentrations of 2 mgL-1 in ACN:water (50:50, v/v), just before infusion experiments. S3 Table SI-1: Target analytes: Class, name, CAS number, molecular formula, molecular weight (MW), pKa and logKow values. Pharmaceuticals detected at >80% of the samples and presented in Figure 1 are highlighted in grey background. Molecular MW Class Compound CAS number pK logK formula (g/mol) a ow a b c MDMA 42542-10-10 C11H15NO2 193.2 9.4 /10.3 2.28 b c Amphetamine-like MDEA 82801-81-9 C12H17NO2 207.3 10.3 2.77 a b c compounds and MDA 4764-17-5 C10H13NO2 179.2 9.67 /9.9 1.84 metabolites Methamphetamine 537-46-3 C H N 149.2 10.1a/10.4b 2.22c (Stimulants) (MA) 10 15 a b c Amphetamine 300-62-10 C9H13N 135.2 10.1 /9.9 1.76 a c Caffeine 58-08-2 C8H10N4O2 194.1 10.4 -0.07 a c Analgesics Paracetamol 103-90-2 C8H9NO2 151.1 9.4 0.46 a c Tramadol 27203-92-5 C16H25NO2 263.2 9.4 2.51 a c Lidocaine 137-58-7 C14H22N2O 234.3 8.0 1.66 a b c Fentanyl 437-38-8 C22H28N2O 336.5 9.0 /8.9, 0.3 3.89 b c Norfentanyl 1609-66-2 C14H20N2O 232.3 9.8, 0.3 1.70 Anesthetics a b c Thiopental 76-75-6 C11H18N2O2S 242.3 7.4 /10.7 2.87 Ketamine 1867-66-10 C13H16ClNO 237.7 7.5a/6.5b 3.12c a c Norketamine 35211-10-1 C12H14ClNO 223.7 6.7 2.66 b c Chloramphenicol 56-75-7 C11H12Cl2N2O5 322.0 7.5 1.14 Antibiotics C H Cl FNO Florfenicol 73231-34-2 12 14 2 4 357.0 6.8b -0.04c (Amphenicols) S b c Thiamphenicol 15318-45-3 C12H15Cl2NO5S 355.0 7.7 -0.27 Antibiotics Trimethoprim 738-70-5 C H N O 290.1 7.1a 0.91c (Bacteriostatic) 14 18 4 3 b c Cefaclor 53994-73-3 C15H16ClN3O4S 367.0 3.0, 7.4 0.35 b c Antibiotics Cefadroxil 66592-87-8 C16H19N3O6S 363.1 3.5, 7.4 -0.06 b c (Cefalosporins) Cefalexin 15686-71-2 C16H17N3O4S 347.1 3.5, 7.4 0.65 b c Cefazolin 25953-19-9 C14H14N8O4S3 454.0 3.0 -0.58 Antibiotics Tiamulin 55297-95-5 C H NO S 493.3 9.5b 4.75c (Diterpene) 28 47 4 a c Azithromycin 83905-01-5 C38H72N2O12 748.5 8.7 4.02 a c Antibiotics Clarithromycin 81103-11-9 C38H69NO13 747.5 9.0 3.16 b c (Macrolides) Lincomycin 154-21-2 C18H34N2O6S 406.2 8.0, 12.4 0.56 b Tylosin 1401-69-0 C46H77NO17 915.5 7.2 - Antibiotics Metronidazole 443-48-1 C H N O 171.1 3.1b 0.02c (Nitroimidazole) 6 9 3 3 Amoxicillin 26787-78-0 C H N O S 365.1 2.4, 7.4b 0.87c Antibiotics 16 19 3 5 C H Cl N O (Penicillins) Dicloxacillin 3116-76-5 19 17 2 3 5 469.0 3.8b 2.91c S b c Antibiotics Ciprofloxacin 85721-33-1 C17H18FN3O3 331.1 5.8, 8.6 0.28 S4 b c (Quinolones) Difloxacin 98106-17-3 C21H19F2N3O3 399.1 5.6, 6.5 1.28 b c Enrofloxacin 93106-60-6 C19H22FN3O3 359.2 5.7, 6.7 0.70 b c Flumequine 42835-25-6 C14H12FNO3 261.1 6.0 2.6 b c Marbofloxacin 115550-35-1 C17H19FN4O4 362.1 5.4, 6.2 -2.92 b c Norfloxacin 70458-96-7 C16H18FN3O3 319.1 5.8, 8.7 -1.03 b c Ofloxacin 82419-36-1 C18H20FN3O4 361.1 5.5, 6.2 -2.00 b c Oxolinic acid 14698-29-4 C13H11NO5 261.1 5.6 0.94 b c Sarafloxacin 98105-99-8 C20H17F2N3O3 385.1 5.8, 8.6 1.07 Sulfachloro- 80-32-0 C H ClN O S 284.0 2.0, 6.5b 0.31c pyridazine 10 9 4 2 b c Sulfaclozine 102-65-8 C10H9ClN4O2S 284.0 2.0, 6.5 0.31 a c Sulfadiazine 68-35-9 C10H10N4O2S 250.1 6.36 -0.09 b c Sulfadimethoxine 122-11-2 C12H14N4O4S 310.1 2.0, 6.9 1.36 b c Sulfadimidine 57-68-1 C12H14N4O2S 278.1 2.0, 7.0 0.89 b c Sulfadoxine 2447-57-6 C12H14N4O4S 310.1 2.3, 6.1 0.70 b c Sulfaguanidine 57-67-0 C7H10N4O2S 214.1 1.0, 3.4 -0.99 Sulfamerazine 127-79-7 C H N O S 264.1 2.0, 7.0b 0.14c Antibiotics 11 12 4 2 b c (Sulfonamides) Sulfamethizole 144-82-1 C9H10N4O2S2 270.0 1.9, 5.5 0.54 b c Sulfamethoxazole 723-46-6 C10H11N3O3S 253.0 2.0, 7.6 0.89 Sulfamethoxypyrida 80-35-3 C H N O S 280.1 2.0, 6.8b 0.32c zine 11 12 4 3 Sulfamonomethoxin 1220-83-3 C H N SO 280.1 2.0, 6.5b 0.31c e 11 12 4 3 b c Sulfamoxole 729-99-7 C11H13N3O3S 267.1 2.0, 6.8 1.03 a c Sulfapyridine 144-83-2 C11H11N3O2S 249.1 8.43 0.35 a c Sulfathiazole 72-14-0 C9H9N3O2S2 255.0 7.2 0.05 a c Sulfisoxazole 127-69-5 C11Χ13Ν3Ο3S 267.1 5.0 1.01 b c Chlortetracycline 57-62-5 C22H23ClN2O8 478.1 4.4 -0.62 b c Antibiotics Doxycycline 564-25-0 C22H24N2O8 444.1 4.6 -0.02 a b c (Tetracyclines) Oxytetracycline 79-57-2 C22H24N2O9 460.1 3.27 /4.6 -0.90 a b c Tetracycline 60-54-8 C22H24N2O8 444.1 3.3 /4.6 -1.30 a c Carbamazepine 298-46-5 C15H12N2O 236.3 4.17,12.5 2.25 a b c Lamotrigine 84057-84-2 C9H7Cl2N5 256.1 5.7 /19.2 0.99 a c Topiramate 97240-79-5 C12H21NO8S 339.4 8.7 -0.33 a c Antiepileptic Levetiracetam 102767-28-3 C8H14N2O2 170.2 <-2 -0.49 a c Phenytoin 57-41-1 C15H12N2O2 252.3 8.3 2.16 a c Primidone 125-33-8 C12H14N2O2 218.3 11.6 0.73 a c Valproic acid 99-66-2 C8H16O2 144.2 4.6 2.96 a c Antihypertensive Atenolol 29122-68-7 C14H22N2O3 266.2 9.6 0.16 a c drugs Propranolol 525-66-6 C16H21NO2 259.2 9.4 3.48 S5 b c Valsartan 137862-53-4 C24H29N5O3 435.2 4.4 3.65 b c Metoprolol 51384-51-1 C15H25NO3 267.2 9.7 1.88 b Atorvastatin 134523-00-5 C33H35FN2O5 558.2 4.3 - b Antilipidemic Simvastatin 79902-63-9 C25H38O5 418.3 4.2 - b c Agents Gemfibrozil 25812-30-0 C15H22O3 250.2 4.4 4.77 b c Clofibric acid 882-09-7 C10H11ClO3 214.0 3.4 2.57 Antiprotozoal Ronidazole 7681-76-7 C H N O 200.0 1.6b -0.38c Agent 6 8 4 4 a c Chlorpromazine 50-53-4 C17H19ClN2S 318.9 9.3 4.32 a c Clozapine 5786-21-1 C18H19ClN4 326.8 3.6, 7.9 3.35 c Norclozapine 6104-71-9 C17H17ClN4 312.8 - 3.01 a c Antipsychotics Olanzapine 132539-06-2 C17H20N4S 312.4 5.0, 7.4 2.56 a c Risperidone 106266-06-3 C23H27FN4O2 410.5 8.3 3.49 c 9-OH-Risperidone 147687-18-2 C23H27FN4O3 426.5 - 1.95 a c Cimetidine 51481-61-9 C10H16N6S 252.1 6.8 0.57 b c Antiulcer Drugs Omeprazole 73590-58-6 C17H19N3O3S 345.1 4.8, 9.7 2.23 b c Ranitidine 66357-35-5 C13H22N4O3S 314.1 8.1 0.27 a c Phenobarbital 50-06-7 C12H12N2O3 232.2 7.5 1.33 Barbiturates a c Pentobarbital 76-74-5 C11H18N2O3 226.3 7.9 2.00 a c Alprazolam 92623-85-4 C17H13ClN4 308.8 8.2 3.87 a c Bromazepam 1812-30-3 C14H10BrN3O 316.2 2.5, 5.2, 11.8 1.93 a b c Chlordiazepoxide 58-25-4 C16H14ClN3O 299.8 4.8 / 8.6, 6.5 -1.57 a c Clobazam 22316-47-9 C16H13ClN2O2 300.7 1.6 1.94 a c Diazepam 439-14-6 C16H13ClN2O 284.7 3.3 2.70 12.0, 3.5a/11.7, Nordiazepam 1088-11-6 C H ClN O 270.7 3.89c 15 11 2 3.2b a c Flunitrazepam 1622-62-5 C16H12FN3O3 313.3 1.71 1.91 Benzodiazepines 7-amine- 34084-50-10 C H FN O 283.3 - 0.78c (Tranquilizers) flunitrazepam 16 14 3 a c Lorazepam
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