PROFICIENCY TESTING SCHEME REPORT. PT-WFD - Pharmaceuticals in Surface Water

Transcription

1 Freie und Hansestadt Hamburg Germany PROFICIENCY TESTING SCHEME REPORT PT-WFD - Pharmaceuticals in Surface Water Bisoprolol, Carbamazepine, Clenbuterol, Diazepam, Diclofenac, Gemfibrozil, Ibuprofen, Iopamidol, Iopromide, Naproxen, Sulfamethoxazole November 2011 provided by Institute for Hygiene and Environment Marckmannstraße 129 b D Hamburg, Germany in cooperation with other European PT providers Hamburg, March 2012 Page 1

2 Cooperation Partner Kemijski Institut Ljubljana Slovenija (National Institute of Chemistry Slovenia) PO Box 660, Hajdrihova 19 - Ljubljana SI-1001 SLOVENIA QUALITYCONSULT "Associazione per lo sviluppo della qualità ambientale" Via G. Bettolo Roma ITALY VITUKI Non-profit Ltd., Quality Assurance and Control Kvassay Jeno út Budapest HUNGARY BIPEA 6/14 av Louis Roche Gennevilliers FRANCE Proftest SYKE, Finnish Environment Institute, Laboratories, Hakuninmaantie 6, FI Helsinki, Finland Tel: 01/ Fax: 01/ info@ki.si Tel: Fax: Qualityconsult@aqc.it Tel: /ext Fax: mecs@vituki.hu Tel:+ 33 (0) Fax: + 33 (0) gmathiaud@bipea.org Tel: Fax: proftest@environment.fi For further information on PT-WFD, please see: Responsibilities: PT-Manager: Dr. Karla Ludwig-Baxter Laboratory Manager: Dipl.-Ing. Carmen Hann Institute for Hygiene and Environment (HU) Marckmannstr. 129 b D Hamburg Germany Tel. +49 (0) / FAX: +49 (0) karla.ludwig-baxter@hu.hamburg.de carmen.hann@hu.hamburg.de /ringversuche Page 2

3 1. General This PT was provided by the Institute for Hygiene and Environment in the context of the PT-WFD network of European PT providers for the determination of Bisoprolol Carbamazepine Clenbuterol Diazepam Diclofenac Gemfibrozil Ibuprofen Iopamidol Iopromide Naproxen Sulfamethoxazole The PT met the requirements of the water framework directive and the related environmental quality standards for the determination of priority substances in surface water. The PT was executed and evaluated due to the requirements of the PT-WFD network. 2. PT design Each participant received the following samples: - 3 x 2 samples for the determination of the mentioned parameters in 1000-ml glass bottles, screw capped with PTFE sealing. The samples were stabilized by cooling. 3. Sample preparation The samples were based on natural surface water. It was initially planned to use surface water containing suspended particulate matter (SPM). However, pre-test results revealed that some of the components were not stable enough in that matrix. Therefore, HU Hamburg decided to use surface water that was filtered using 1 µm cartridges to eliminate particulate matter and autoclaved instead. 4. Parameters to be analyzed Parameter (CAS-number, MW: molecular weight) Bisoprolol (CAS ; MW 325,45 g/mol) Carbamazepine (CAS ; MW 236,27 g/mol) Clenbuterol (CAS ; MW 277,19 g/mol) Diazepam (CAS ; MW 284,75 g/mol) Diclofenac (CAS ; MW 296,15 g/mol) Gemfibrozil (CAS ; MW 250,34 g/mol) Ibuprofen (CAS ; MW 206,28 g/mol) Iopamidol (CAS ; MW 777,09 g/mol) Iopromide (CAS ; MW 792,11 g/mol) Naproxen (CAS ; MW 230,26 g/mol) AA-EQS [µg/l] * 0.01** Sulfamethoxazole 0.1 (CAS ; MW 253,31 g/mol) *: Discussed in Germany as specific synthetic pollutant for ecological status or potential classification for a body of surface water according to directive 2000/60/EC. Page 3

4 **: Discussed in the EU as priority substance for chemical status classification for a body of surface water according to directive 2000/60/EC. Some of these parameters are taken from annex A (priority substances) of the Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on environmental quality standards in the field of water policy and Amending Directive 2000/60/EC. This directive sets Environmental Quality Standards (EQS) for different substances. The allowed annual average EQS (AA-EQS) for the above mentioned parameters in inland surface waters is given in the table above. In the last Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL for a change of the directive 2000/60 EG and 2008/105/EG in regard of priority substances in the field of water policy from 31 st January 2012 Diclofenac is the only pharmaceutical mentioned with a AA-EQS of 0.1 µg/l. Table 1: Selected pharmaceuticals (Bold: substances, which might be included in the EU-list) Pharmaceutical used as EQS [µg/l] Consumption [kg]/a * Structure Bisoprolol Beta-blocker Carbamazepine Anti-epileptic drug Clenbuterol Anti-asthma drug Diazepam Psychopharm acon 0.1 or Diclofenac Analgetic / antiinflammatory drug Gemfibrozil Lipid-lowering agent Page 4

5 Continuation: Table 1: Selected pharmaceuticals (Bold: substances, which might be included in the EUlist) Pharmaceutical used as EQS [µg/l] Consumption [kg]/a * Structure Ibuprofen Analgetic / antiinflammatory drug Iopamidol Iodinated X- ray contrast agent Iopromide Iodinated X- ray contrast agent Naproxen Antiinflammatory drug Sulfamethoxazole Antibiotic *:from BLAC-Bericht Arzneimittel in der Umwelt, Sample distribution The samples were dispatched on the 23 rd November 2011 by express service. Before dispatch freezer packs had been added to the packages. Laboratories which had registered with the cooperation partner were supplied with samples by them. The participants were advised to store the samples immediately after receipt at low temperature (4 ºC) and to start the analysis of the samples as soon as possible. 6. Analytical methods Participants had been free to choose a suitable method. The analytical method should comply with the request of a limit of quantification (LOQ) of 0,025 µg/l. The LOQ is based on the requirements of article 4 of the Draft commission directive of the European communities for the technical specification for chemical analysis and monitoring of water status in the context of the water framework directive. The limit corresponds to 30% of the environmental quality standards (EQS) of the directive 2008/105/EG on environmental quality standards in the field of water policy. The samples had to be analysed in duplicate over the complete method (sample preparation and measurement). The participants were asked to submit the results as average values in µg/l with three significant digits. Page 5

6 7. Submission of results The deadline for the submission of results was the 23rd December Evaluation and assessment Assigned values: The statistical evaluation was carried out using Algorithm A mean from ISO for calculation of the mean. The consensus mean was used as assigned value (X). Standard deviation for proficiency assessment (SDPA): The standard deviation for proficiency assessment (SDPA) is calculated in compliance with the requirements of the PT-WFD network: SDPA = 0.25 * X. Assessment: For each measurement value x, a z-score is calculated from the assigned value X and SDPA according to following formula: ( x X ) z = SDPA The assessment of the results is as follows: z-score 2.0: Satisfactory result 2.0 < z-score < 3.0: Questionable result z-score 3.0: Unsatisfactory result 9. Uncertainty of the Mean The uncertainties of the mean values of participants results were calculated according to ISO (Statistical Methods for Use in Proficiency Testing by Interlaboratory Comparisons) as U mean = 2 * 1.25 * SR / N SR: reproducibility standard deviation N: number of data for this level 2: coverage factor for the expanded uncertainty 1.25: correction factor (according to ISO to be used for robust methods) 10. Participation Number of participants (total): 35 Registration via HU Hamburg: 32 via Kemijski Institut, Slovenija: 0 via VITUKI, Hungary: 2 via Proftest SYKE, Finland: 1 via BIPEA, France: 0 via QUALITYCONSULT, Italy: 0 Page 6

7 11. Discussion of results In the table below the data of the PT are listed (number of results, mean (consensus values), standard deviation, calculated using robust statistics [µg/l], standard deviation for proficiency assessment [µg/l] and [%]). Table 11.1 : Data for level 1 Parameter Number Assigned U mean uncertainty Standard deviation Standard deviation of results value [µg/l] of the assigned value [µg/l] calc. using robust statistics SR[µg/l] and VR[%] for PT assessment SR[µg/l] and VR[%] Bisoprolol 15 0,701 0,103 0,160 22,9 0,175 25,0 Carbamazepine 22 0,230 0,013 0,024 10,3 0,058 25,0 Clenbuterol 16 0,277 0,023 0,036 13,1 0,069 25,0 Diazepam 14 0,181 0,019 0,028 15,8 0,045 25,0 Diclofenac 22 0,481 0,060 0,112 23,2 0,120 25,0 Gemfibrozil 13 0,128 0,010 0,015 11,7 0,032 25,0 Ibuprofen 20 0,369 0,036 0,064 17,4 0,092 25,0 Iopamidol 20 0,246 0,031 0,055 22,6 0,062 25,0 Iopromide 20 0,128 0,017 0,031 24,2 0,032 25,0 Naproxen 16 0,121 0,017 0,027 22,0 0,030 25,0 Sulfamethoxazole 21 0,158 0,016 0,029 18,2 0,040 25,0 Table 11.2 : Data for level 2 Parameter Number Assignd U mean uncertainty Standard deviation Standard deviation of results value [µg/l] of the assigned value [µg/l] calc. using robust statistics SR[µg/l] and VR[%] for PT assessment SR[µg/l] and VR[%] Bisoprolol 14 0,201 0,030 0,045 22,6 0,050 25,0 Carbamazepine 21 0,340 0,026 0,048 14,1 0,085 25,0 Clenbuterol 16 0,113 0,014 0,022 19,3 0,028 25,0 Diazepam 15 0,319 0,032 0,049 15,4 0,080 25,0 Diclofenac 21 0,598 0,064 0,118 19,7 0,150 25,0 Gemfibrozil 15 0,181 0,040 0,062 34,2 0,045 25,0 Ibuprofen 20 0,114 0,012 0,021 18,7 0,029 25,0 Iopamidol 19 0,359 0,059 0,102 28,5 0,090 25,0 Iopromide 19 0,223 0,028 0,049 21,9 0,056 25,0 Naproxen 17 0,191 0,027 0,045 23,7 0,048 25,0 Sulfamethoxazole 19 0,312 0,031 0,054 17,4 0,078 25,0 Page 7

8 Table 11.3 : Data for level 3 Standard deviation Number Assigned U mean uncertainty Standard deviation calc. using robust Parameter of value of the assigned for PT assessment statistics results [µg/l] value [µg/l] SR[µg/l] and VR[%] SR[µg/l] and VR[%] Bisoprolol 18 0,205 0,030 0,051 24,9 0,051 25,0 Carbamazepine 25 0,337 0,022 0,044 13,0 0,084 25,0 Clenbuterol 19 0,102 0,010 0,017 16,6 0,026 25,0 Diazepam 18 0,292 0,026 0,044 15,2 0,073 25,0 Diclofenac 25 0,572 0,060 0,199 20,8 0,143 25,0 Gemfibrozil 20 0,168 0,025 0,044 26,4 0,042 25,0 Ibuprofen 24 0,139 0,015 0,029 20,8 0,035 25,0 Iopamidol 23 0,361 0,062 0,118 32,6 0,090 25,0 Iopromide 23 0,212 0,036 0,069 32,7 0,053 25,0 Naproxen 22 0,182 0,025 0,046 25,5 0,046 25,0 Sulfamethoxazole 23 0,268 0,032 0,062 23,2 0,067 25,0 Table 11.4 : Data for level 4 Parameter Number Assigned U mean uncertainty Standard deviation Standard deviation of results value [µg/l] of the assigned value [µg/l] calc. using robust statistics SR[µg/l] and VR[%] for PT assessment SR[µg/l] and VR[%] Bisoprolol 16 0,371 0,070 0,112 30,2 0,093 25,0 Carbamazepine 25 0,126 0,006 0,012 9,8 0,032 25,0 Clenbuterol 18 0,162 0,009 0,016 9,6 0,041 25,0 Diazepam 16 0,131 0,018 0,029 23,4 0,033 25,0 Diclofenac 25 0,311 0,032 0,063 20,4 0,078 25,0 Gemfibrozil 18 0,329 0,035 0,059 17,8 0,082 25,0 Ibuprofen 23 0,281 0,017 0,033 11,7 0,070 25,0 Iopamidol 22 0,140 0,017 0,031 22,4 0,035 25,0 Iopromide 22 0,354 0,044 0,082 23,2 0,089 25,0 Naproxen 20 0,327 0,038 0,068 20,9 0,082 25,0 Sulfamethoxazole 23 0,409 0,041 0,079 19,3 0,102 25,0 As can be seen from the results, the standard deviation VR calculated here with a robust statistic method called Q-method (ProLab, quodata, Dresden) shows values ranging from 9,6 % to 34,2 %, depending on the compound and concentration level. This is what could be expected for that kind of analytic and these results are very satisfactory. Assessment results The following table and graphic display the number of satisfactory, questionable and unsatisfactory results for each parameter. Page 8

9 Table: 11.5 Number and percentage of satisfactory, questionable and unsatisfactory results Parameter Z 2 3 < Z > 2 Z 3 Bisoprolol 58 (92,0%) 2 (3,2%) 3 (4,7%) Carbamazepine 91 (98,9%) 1 (1,1%) 0 Clenbuterol 64 (92,8%) 2 (2,9%) 3 (4,3%) Diazepam 62 (98,4%) 1 (1,6%) 0 Diclofenac 83 (90,2%) 2 (2,2%) 7 (7,6%) Gemfibrozil 59 (89,4%) 2 (3,0%) 5 (7,6%) Ibuprofen 82 (92,1%) 4 (4,5%) 3 (3,3%) Iopamidol 74 (88,1%) 5 (6,0%) 5 (6,0%) Iopromide 69 (82,1%) 7 (8,3%) 8 (9,5%) Naproxen 69 (92,0%) 4 (5,3%) 2 (2,7%) Sufamethoxazole 79 (91,9%) 5 (5,8%) 2 (2,3%) Graphic 11.1: Number of satisfactory, questionable and unsatisfactory results As to be seen from the data, there are just very few questionable and unsatisfactory z-scores. Many of the laboratories seem to be well experienced with the determination of these substances. The following table shows the initial concentration of the substances in the matrix, the added spike as well as the mean calculated with the data of the participants (consensus value). Page 9

10 Table 11.6: Level 1 Recovery rates Parameter Conc. in Added Conc. in spiked Assigned Recovery matrix spike sample value rate [µg/l] [µg/l] [µg/l] [µg/l] [%] Bisoprolol 0, ,638 0,644 0, ,8 Carbamazepine 0,0523 0,183 0,235 0,23 97,7 Clenbuterol 0, ,257 0,257 0, ,7 Diazepam 0, ,175 0,176 0, ,0 Diclofenac 0,175 0,267 0,442 0, ,8 Gemfibrozil 0, ,117 0,117 0, ,0 Ibuprofen 0, ,367 0,369 0,369 99,9 Iopamidol 0, ,242 0,250 0,246 98,3 Iopromide 0, ,125 0,127 0, ,9 Naproxen 0, ,108 0,111 0, ,5 Sulfamethoxazole 0,0395 0,100 0,140 0, ,3 Table 11.7 Level 2 Recovery rates Parameter Conc. in Added Conc. in spiked Assigned Recovery matrix spike sample value rate [µg/l] [µg/l] [µg/l] [µg/l] [%] Bisoprolol 0, ,177 0,184 0, ,4 Carbamazepine 0,0541 0,292 0,346 0,34 98,2 Clenbuterol nn 0,095 0,095 0, ,9 Diazepam 0, ,325 0,326 0,319 97,8 Diclofenac 0,175 0,4 0,575 0, ,0 Gemfibrozil 0, ,167 0,168 0, ,1 Ibuprofen 0, ,1 0,102 0, ,2 Iopamidol 0, ,358 0,366 0,359 98,2 Iopromide 0, ,225 0,226 0,223 98,6 Naproxen 0, ,183 0,186 0, ,6 Sulfamethoxazole 0,043 0,267 0,310 0, ,6 Table 11.8 Level 3 Recovery rates Parameter Conc. in Added Conc. in spiked Assigned Recovery matrix spike sample value rate [µg/l] [µg/l] [µg/l] [µg/l] [%] Bisoprolol 0, ,198 0,201 0, ,1 Carbamazepine 0,0559 0,308 0,364 0,337 92,6 Clenbuterol 0, ,081 0,081 0, ,9 Diazepam 0, ,283 0,285 0, ,4 Diclofenac 0,187 0,350 0,537 0, ,5 Gemfibrozil 0, ,142 0,143 0, ,5 Ibuprofen 0, ,108 0,110 0, ,1 Iopamidol 0, ,408 0,415 0,361 87,1 Iopromide 0, ,250 0,251 0,212 84,5 Naproxen 0, ,175 0,178 0, ,1 Sulfamethoxazole 0,0416 0,233 0,275 0,268 97,6 Page 10

11 Table 11.9 Level 4 Recovery rates Parameter Conc. in matrix [µg/l] Added spike [µg/l] Conc. in spiked sample [µg/l] Assigned value [µg/l] Recovery rate [%] Bisoprolol 0, ,354 0,360 0, ,2 Carbamazepine 0,0576 0,067 0,125 0, ,1 Clenbuterol 0, ,147 0,149 0, ,6 Diazepam 0, ,117 0,120 0, ,6 Diclofenac 0,187 0,108 0,295 0, ,4 Gemfibrozil 0, ,325 0,326 0, ,0 Ibuprofen 0, ,267 0,268 0, ,9 Iopamidol 0, ,125 0,132 0, ,2 Iopromide 0, ,375 0,375 0,354 94,4 Naproxen 0, ,342 0,346 0,327 94,5 Sulfamethoxazole 0,0407 0,400 0,441 0,409 92,8 Attention: The concentrations of the pharmaceuticals in the spiked samples have been determined by using common analytical procedures and do not comply with the criteria used for a reference material. Problems with calibration At one point of the evaluation it became obvious that for the two substances Bisoprolol and Clenbuterol there were implausible values and the standard deviation was much higher than for most of the other compounds. The reason for that discrepancy was found when considering the form of the commonly commercially available standards. Although we wanted all labs to use the molecular weight of the effective substance (active ingredient) for calculating the contents some participants had used the compounds salts like fumerates, hemifumerates, hydrogen chlorides, etc. Whereas in some cases there is not much difference in the molecular weight like with Diclofenac*Na, others like the fumerates change the molecular weight much more. To be able to perform a decent evaluation we decided to give the participants a once off chance to do a mathematical correction of their already delivered data. With the partly changed collective, a new evaluation and assessment for Bisoprolol and Clenbuterol was performed. Page 11

12 11. Analytical Methods The participants were free to choose a suitable method as long as the method applied to the requirement of this PT. As mentioned before there was a limit of detection (LOD) set to 0,025 µg/l for each component. Table 11.1 Applied analysis methods and sample preparation Applied methods Parameter HPLC/MSMS GC/MS Applied sample preparation with without enrichm. enrichm.* Bisoprolol Carbamazepine Clenbuterol Diazepam Diclofenac Gemfibrozil Ibuprofen Iopamidol Iopromide Naproxen Sulfamethoxazole *: direct injection The vast majority of participants used HPLC/MSMS. Depending on the substance, the laboratories chose to use enrichment before measurement or did direct injection. Only Carbamazepine, Diclofenac, Ibuprofen and Naproxen were determined by one and three laboratories, respectively, using GC/MS. Graphic 11.1 Applied analysis methods and sample preparation Page 12

13 12. Conclusion The PT-WFD Pharmaceuticals in Surface Water was carried out in November The target of the PT was to measure the content of 11 selected pharmaceuticals (Bisoprolol, Carbamazepine, Clenbuterol, Diazepam, Diclofenac, Gemfibrozil, Ibuprofen, Iopamidol, Iopromide, Naproxen, Sulfamethoxazole). Because of their high commercial use and their persistence, these substances are already detectable in numerous surface waters. Therefore, one of them (Diclofenac) has been included in the new EU list of priority substances from 31 st January, The PT was performed in the frame of the joint PT-WFD European network in cooperation with partner institutions. The Institute of Hygiene and Environment in Hamburg, Germany, acted as the central organizer working together with 5 cooperation partners from Finland, France, Italy, Hungary and Slovenia. 35 participants from 4 countries were investigating three samples out of four different levels. The evaluation was performed using Algorithm A from ISO for calculation of the mean (consensus value used as assigned value X). A standard deviation for proficiency assessment (SDPA) SDPA = 025 * X was applied. The results showed that most of the laboratories had very good experience in determining these kinds of substances. The most commonly applied technique for analyzing was HPLC/MSMS. Just three laboratories used GCMS for about five of the compounds. The recovery rates for the 11 compounds range between 85,5 % und 126,1 %. The division of the Z-scores into three classes (z 2: satisfactory; 3 z 2: questionable and z 3: unsatisfactory) showed that on an average 91.6 % of the results were satisfactory; 4.0 % of all results were questionable and 4.4 % unsatisfactory. Page 13

14 Bisoprolol, level 1 R e s u l t s Assigned value X [µg/l] (mean): 0,701 Standard deviation for Proficiency Assessment (0,25 * X) = 0,175 [µg/l] Conc. in spiked sample [µg/l] = 0, ,39-1, ,753 0,3 2 0,509-1, ,77 0, ,545-0, ,772 0, ,609-0, ,791 0, ,636-0, ,821 0, ,661-0, ,891 1, ,673-0, ,894 1, ,723 0,128 Page 14

15 Bisoprolol, level 2 Assigned value X [µg/l] (mean): 0,201 Standard deviation for Proficiency Assessment (0,25 * X) = 0,05 Conc. in spiked sample [µg/l] = 0,184 Labcode mean Z-Score Labcode mean Z-Score 23 0,042-3, ,197-0, ,108-1, ,198-0, ,117-1, ,215 0, ,177-0, ,262 1, ,178-0, ,271 1, ,184-0, ,282 1, ,196-0, ,283 1,635 Page 15

16 Bisoprolol, level 3 Assigned value X [µg/l] (mean): 0,205 Standard deviation for Proficiency Assessment (0,25 * X) = 0,051 Conc. in spiked sample [µg/l] = 0, ,043-3, ,224 0, ,066-2, ,225 0, ,111-1, ,238 0, ,135-1, ,242 0, ,173-0, ,244 0, ,189-0, ,248 0, ,201-0, ,256 0, ,208 0, ,323 2, ,22 0, ,224 0,365 Page 16

17 Bisoprolol, level 4 Assigned value X [µg/l] (mean): 0,371 Standard deviation for Proficiency Assessment (0,25 * X) = 0,093 Conc. in spiked sample [µg/l] = 0,360 Labcode mean Z-Score Labcode mean Z-Score 23 0,077-3, ,386 0, ,219-1, ,413 0, ,243-1,38 7 0,42 0, ,309-0, ,423 0, ,335-0, ,431 0, ,339-0, ,48 1, ,364-0, ,485 1, ,378 0, ,509 1,487 Page 17

18 Carbamazepine, level 1 Assigned value X [µg/l] (mean): 0,230 Standard deviation for Proficiency Assessment (0,25 * X) = 0,058 Conc. in spiked sample [µg/l] = 0, ,126-1, ,232 0, ,185-0, ,236 0, ,207-0, ,238 0, ,212-0, ,239 0,15 7 0,216-0,25 8 0,24 0, ,221-0, ,249 0, ,222-0, ,25 0, ,224-0, ,253 0, ,225-0, ,272 0, ,227-0, ,372 2, ,228-0, ,228-0,041 Page 18

19 Carbamazepine, level 2 Assigned value X [µg/l] (mean): 0,340 Standard deviation for Proficiency Assessment (0,25 * X) = 0,085 Conc. in spiked sample [µg/l] = 0, ,278-0, ,339-0, ,281-0, , ,3-0, ,342 0, ,301-0, ,36 0, ,304-0, ,361 0, ,31-0, ,366 0, ,328-0, ,384 0, ,33-0, ,393 0, ,334-0, ,402 0, ,336-0, ,42 0, ,338-0,023 Page 19

20 Carbamazepine, level 3 Assigned value X [µg/l] (mean): 0,337 Standard deviation for Proficiency Assessment (0,25 * X) = 0,084 Conc. in spiked sample [µg/l] = 0, ,235-1, ,342 0, ,236-1, ,344 0, ,284-0, ,352 0, ,288-0, ,352 0, ,293-0, ,356 0, ,306-0, ,362 0, ,319-0, ,365 0, ,32-0,2 15 0,37 0, ,321-0, ,379 0, ,331-0, ,387 0, ,334-0, ,394 0, ,338 0, ,419 0, ,339 0, ,342 0, ,36 0, ,361 0, ,366 0, ,384 0,624 Page 20

21 Carbamazepine, level 4 Assigned value X [µg/l] (mean): 0,126 Standard deviation for Proficiency Assessment (0,25 * X) = 0,032 Conc. in spiked sample [µg/l] = 0,125 Labcode mean Z-Score Labcode Mean Z-Score 12 0,078-1, ,13 0, ,086-1, ,135 0, ,107-0, ,14 0, ,111-0, ,141 0, ,113-0, ,144 0, ,114-0, ,146 0, ,122-0, ,147 0, ,122-0, ,13 0, ,123-0, ,135 0, ,124-0, ,14 0, ,126-0, ,141 0, ,126-0, ,144 0, ,127 0, ,146 0, ,127 0, ,147 0, ,129 0, ,129 0, ,129 0, ,13 0,121 Page 21

22 Clenbuterol, level 1 Assigned value X [µg/l] (mean): 0,277 Standard deviation for Proficiency Assessment (0,25 * X) = 0,069 Conc. in spiked sample [µg/l] = 0, ,23-0, ,284 0, ,242-0, ,288 0, ,243-0, ,292 0, ,247-0, ,296 0, ,249-0, ,298 0, ,257-0, ,303 0, ,267-0, ,332 0, ,27-0, ,795 7,49 Page 22

23 Clenbuterol, level 2 Assigned value X [µg/l] (mean): 0,113 Standard deviation for Proficiency Assessment (0,25 * X) [µg/l ]= 0,028 Conc. in spiked sample [µg/l] = 0, ,08-1, ,112-0, ,094-0, ,113-0, ,095-0, ,12 0, ,096-0, ,121 0, ,098-0, ,123 0, ,104-0, ,15 1, ,105-0, ,164 1, ,111-0, ,194 2,858 Page 23

24 Clenbuterol, level 3 Assigned value X [µg/l] (mean): 0,102 Standard deviation for Proficiency Assessment (0,25 * X) = 0,026 Conc. in spiked sample [µg/l] = 0, ,07-1, ,1-0, ,084-0, ,103 0, ,086-0, ,106 0, ,089-0, ,106 0, ,091-0, ,11 0, ,097-0, ,114 0, ,098-0, ,143 1, ,098-0, ,164 2, ,098-0, ,23 5, ,099-0,117 Page 24

25 Clenbuterol, level 4 Assigned value X [µg/l] (mean): 0,162 Standard deviation for Proficiency Assessment (0,25 * X) = 0,041 Conc. in spiked sample [µg/l] = 0,149 Labcode mean Z-Score Labcode mean Z-Score 8 0,13-0, ,166 0, ,144-0, ,168 0, ,147-0, ,171 0, ,148-0, ,172 0, ,152-0, ,173 0, ,153-0, ,173 0, ,154-0, ,177 0, ,154-0,2 23 0,195 0, ,16-0,06 1 0,358 4,817 Page 25

26 Diazepam, level 1 Assigned value X [µg/l] (mean): 0,181 Standard deviation for Proficiency Assessment (0,25 * X) = 0,045 Conc. in spiked sample [µg/l] = 0, ,141-0, ,172-0, ,152-0, ,179-0, ,159-0, ,185 0, ,164-0, ,205 0,54 2 0,166-0, ,22 0, ,169-0, ,225 0, ,17-0, ,279 2,179 Page 26

27 Diazepam, level 2 Assigned value X [µg/l] (mean): 0,319 Standard deviation for Proficiency Assessment (0,25 * X) = 0,080 Conc. in spiked sample [µg/l] = 0, ,211-1, ,32 0, ,245-0, ,345 0, ,284-0, ,353 0, ,29-0, ,355 0, ,297-0, ,367 0, ,304-0, ,373 0, ,304-0, ,417 1, ,306-0,16 Page 27

28 Diazepam, level 3 Assigned value X [µg/l] (mean): 0,292 Standard deviation for Proficiency Assessment (0,25 * X) = 0,073 Conc. in spiked sample [µg/l] = 0, ,23-0, ,287-0, ,249-0, ,31 0, ,25-0, ,317 0, ,252-0, ,321 0, ,267-0, ,322 0, ,272-0, ,326 0, ,283-0, ,37 1, ,284-0,11 3 0,425 1, ,284-0, ,285-0,096 Page 28

29 Diazepam, level 4 Assigned value X [µg/l] (mean): 0,131 Standard deviation for Proficiency Assessment (0,25 * X) = 0,033 Conc. in spiked sample [µg/l] = 0, ,097-1, ,129-0, ,098-0, ,13-0, ,11-0, ,14 0, ,111-0,6 13 0,146 0, ,111-0,6 19 0,146 0, ,115-0, ,167 1, ,119-0, ,19 1, ,122-0, ,195 1,973 Page 29

30 Diclofenac, level 1 Assigned value X [µg/l] (mean): 0,481 Standard deviation for Proficiency Assessment (0,25 * X) = 0,120 Conc. in spiked sample [µg/l] = 0,442 Labcode mean Z-Score Labcode mean Z-Score 28 0,078-3, ,485 0, ,332-1, ,493 0, ,353-1, ,494 0, ,395-0, ,501 0, ,412-0, ,532 0, ,426-0, ,552 0, ,442-0, ,565 0, ,446-0, ,585 0, ,447-0, ,605 1, ,45-0, ,671 1, ,452-0, ,189 5,893 Page 30

31 Diclofenac, level 2 Assigned value X [µg/l] (mean): 0,598 Standard deviation for Proficiency Assessment (0,25 * X) = 0,150 Conc. in spiked sample [µg/l] = 0, ,16-2, ,591-0, ,371-1, ,61 0, ,514-0, ,615 0, ,514-0, ,635 0, ,517-0, ,649 0, ,53-0, ,668 0, ,563-0, ,702 0, ,58-0, ,727 0, ,581-0, ,795 1, ,584-0, ,087 3, ,59-0,055 Page 31

32 Diclofenac, level 3 Assigned value X [µg/l] (mean):0,572 Standard deviation for Proficiency Assessment (0,25 * X) = 0,143 Conc. in spiked sample [µg/l] = 0, ,32-1, ,547-0, ,342-1, ,564-0, ,443-0, ,596 0, ,471-0, ,617 0, ,484-0, ,64 0, ,51-0, ,651 0, ,531-0, ,652 0, ,532-0, ,666 0, ,533-0, ,68 0, ,537-0, ,723 1, ,54-0,22 5 0,907 2, ,542-0, ,165 4, ,542-0,203 Page 32

33 Diclofenac, level 4 Assigned value X [µg/l] (mean): 0,311 Standard deviation for Proficiency Assessment (0,25 * X) = 0,078 Conc. in spiked sample [µg/l] = 0, ,053-3, ,304-0, ,203-1, ,306-0,06 1 0,238-0, ,307-0, ,259-0, ,318 0, ,267-0, ,34 0, ,27-0, ,361 0, ,272-0, ,37 0, ,278-0, ,391 1, ,284-0, ,399 1, ,285-0, ,401 1, ,289-0, ,591 3,61 2 0,29-0, ,627 4, ,295-0,202 Page 33

34 Gemfibrozil, level 1 Assigned value X [µg/l] (mean): 0,128 Standard deviation for Proficiency Assessment (0,25 * X) = 0,032 Conc. in spiked sample [µg/l] = 0, ,109-0, ,126-0, ,114-0, ,131 0, ,114-0,45 3 0,145 0, ,115-0, ,165 1, ,119-0, ,168 1, ,12-0, ,244 3, ,124-0,138 Page 34

35 Gemfibrozil, level 2 Assigned value X [µg/l] (mean): 0,181 Standard deviation for Proficiency Assessment (0,25 * X) = 0,045 Conc. in spiked sample [µg/l] = 0,168 1,84 Labcode mean Z-Score Labcode mean Z-Score 9 0,084-2, ,183 0, ,125-1, ,19 0, ,131-1, ,203 0, ,152-0, ,218 0, ,156-0, ,231 1, ,159-0, ,378 4, ,162-0, ,84 36, ,175-0,143 Page 35

36 Gemfibrozil, level 3 Assigned value X [µg/l] (mean): 0,168 Standard deviation for Proficiency Assessment (0,25 * X) = 0,042 Conc. in spiked sample [µg/l] = 0, ,1-1, ,165-0, ,115-1, ,173 0, ,126-1, ,178 0, ,135-0, ,187 0, ,141-0, ,19 0, ,144-0, ,19 0, ,144-0, ,193 0,59 7 0,153-0, ,245 1, ,16-0, ,258 2, ,164-0,1 32 0,641 11,245 Page 36

37 Gemfibrozil, level 4 Assigned value X [µg/l] (mean): 0,329 Standard deviation for Proficiency Assessment (0,25 * X) = 0,082 Conc. in spiked sample [µg/l] = 0, ,208-1, ,33 0, ,27-0, ,335 0, ,284-0, ,345 0, ,287-0, ,347 0, ,298-0, ,374 0, ,301-0, ,378 0, ,304-0, ,382 0, ,308-0, ,398 0, ,325-0,05 5 0,602 3,317 Page 37

38 Ibuprofen, level 1 Assigned value X [µg/l] (mean): 0,369 Standard deviation for Proficiency Assessment (0,25 * X) = 0,092 Conc. in spiked sample [µg/l] = 0, ,18-2, ,378 0, ,244-1, ,396 0, ,261-1, ,396 0, ,328-0, ,396 0, ,328-0, ,402 0, ,33-0, ,403 0, ,353-0, ,409 0, ,361-0, ,415 0, ,365-0, ,464 1, ,374 0, ,518 1,614 Page 38

39 Ibuprofen, level 2 Assigned value X [µg/l] (mean): 0,114 Standard deviation for Proficiency Assessment (0,25 * X) = 0,029 Conc. in spiked sample [µg/l] = 0, ,044-2, ,114-0, ,092-0, ,118 0, ,096-0, ,119 0, ,097-0, ,125 0, ,1-0, ,128 0, ,1-0, ,129 0, ,103-0, ,13 0, ,105-0, ,133 0, ,108-0, ,167 1, ,11-0, ,41 10,381 Page 39

40 Ibuprofen, level 3 Assigned value X [µg/l] (mean): 0,139 Standard deviation for Proficiency Assessment (0,25 * X) = 0,035 Conc. in spiked sample [µg/l] = 0, ,09-1, ,135-0, ,107-0, ,139 0, ,11-0, ,14 0, ,11-0, ,145 0, ,118-0, ,148 0, ,119-0, ,153 0, ,121-0, ,157 0,52 6 0,129-0, ,157 0, ,129-0, ,178 1, ,131-0, ,194 1, ,132-0, ,265 3, ,134-0, ,312 4,983 Page 40

41 Ibuprofen, level 4 Assigned value X [µg/l] (mean): 0,281 Standard deviation for Proficiency Assessment (0,25 * X) = 0,070 Conc. in spiked sample [µg/l] = 0, ,15-1, ,29 0, ,238-0, ,291 0, ,253-0,4 7 0,292 0, ,256-0, ,293 0, ,256-0, ,296 0, ,257-0, ,301 0, ,257-0, ,302 0, ,259-0, ,307 0, ,262-0, ,365 1, ,27-0, ,381 1, ,276-0, ,392 1, ,287 0,084 Page 41

42 Iopamidol, level 1 Assigned value X [µg/l] (mean): 0,246 Standard deviation for Proficiency Assessment (0,25 * X) = 0,062 Conc. in spiked sample [µg/l] = 0,250 Labcode Mean Z-Score Labcode Mean Z-Score 6 0,092-2, ,248 0, ,178-1, ,255 0, ,191-0, ,26 0, ,195-0, ,261 0, ,209-0, ,272 0, ,216-0, ,296 0,82 5 0,223-0, ,297 0, ,234-0, ,297 0, ,245-0, ,298 0, ,247 0, ,586 5,541 Page 42

43 Iopamidol, level 2 Assigned value X [µg/l] (mean): 0,359 Standard deviation for Proficiency Assessment (0,25 * X) = 0,090 Conc. in spiked sample [µg/l] = 0, ,375 0, ,159-2, ,379 0, ,219-1, ,39 0, ,31-0, ,417 0, ,32-0, ,42 0, ,322-0, ,441 0, ,329-0, ,45 1, ,332-0, ,453 1, ,37 0, ,551 2, ,372 0,144 Page 43

44 Iopamidol, level 3 Assigned value X [µg/l] (mean): 0,361 Standard deviation for Proficiency Assessment (0,25 * X) = 0,090 Conc. in spiked sample [µg/l] =0, ,398 0, ,136-2, ,403 0, ,174-2, ,414 0, ,193-1, ,419 0, ,243-1, ,429 0, ,29-0, ,442 0, ,296-0, ,46 1, ,322-0, ,467 1, ,353-0, ,473 1, ,365 0, ,49 1, ,378 0, ,531 1, ,385 0,265 Page 44

45 Iopamidol, level 4 Assigned value X [µg/l] (mean): 0,140 Standard deviation for Proficiency Assessment (0,25 * X) = 0,035 Conc. in spiked sample [µg/l] = 0, ,143 0,09 5 0,075-1, ,149 0, ,11-0, ,15 0, ,113-0, ,151 0, ,118-0, ,155 0, ,12-0, ,156 0, ,129-0, ,159 0, ,129-0, ,168 0, ,13-0, ,168 0, ,13-0, ,204 1, ,14 0, ,371 6,611 Page 45

46 Iopromide, level 1 Assigned value X [µg/l] (mean): 0,128 Standard deviation for Proficiency Assessment (0,25 * X) = 0,032 Conc. in spiked sample [µg/l] = 0, ,029-3, ,139 0,33 6 0,033-2, ,14 0, ,06-2, ,143 0, ,08-1, ,144 0, ,11-0, ,144 0, ,118-0, ,146 0, ,12-0, ,148 0, ,122-0,2 27 0,153 0, ,128-0, ,175 1, ,136 0, ,24 3,476 Page 46

47 Iopromide, level 2 Assigned value X [µg/l] (mean): 0,223 Standard deviation for Proficiency Assessment (0,25 * X) = 0,056 Conc. in spiked sample [µg/l] = 0, ,231 0, ,049-3, ,236 0, ,072-2, ,242 0, ,164-1, ,253 0, ,205-0, ,259 0, ,209-0, ,264 0, ,22-0, ,266 0, ,223-0, ,269 0, ,227 0, ,297 1, ,23 0,117 Page 47

48 Iopromide, level 3 Assigned value X [µg/l] (mean): 0,212 Standard deviation for Proficiency Assessment (0,25 * X) = 0,053 Conc. in spiked sample [µg/l] = 0, ,236 0, ,052-3, ,24 0, ,067-2, ,24 0, ,073-2, ,255 0,82 2 0,097-2, ,265 1, ,119-1, ,268 1, ,155-1, ,276 1, ,203-0, ,277 1, ,221 0, ,291 1,5 4 0,223 0, ,297 1, ,225 0, ,303 1, ,234 0,423 Page 48

49 Iopromide, level 4 Assigned value X [µg/l] (mean): 0,354 Standard deviation for Proficiency Assessment (0,25 * X) = 0,089 Conc. in spiked sample [µg/l] = 0, ,365 0, ,05-3, ,377 0, ,165-2, ,385 0, ,225-1, ,392 0, ,319-0, ,398 0, ,32-0,38 4 0,402 0, ,334-0, ,404 0, ,34-0, ,415 0, ,343-0,12 1 0,444 1, ,347-0, ,448 1, ,348-0, ,484 1,475 Page 49

50 Naproxen, level 1 Assigned value X [µg/l] (mean): 0,121 Standard deviation for Proficiency Assessment (0,25 * X) = 0,030 Conc. in spiked sample [µg/l] = 0, ,076-1, ,12-0, ,082-1, ,121-0, ,094-0, ,13 0, ,108-0, ,131 0, ,109-0, ,141 0, ,114-0, ,148 0, ,118-0, ,198 2, ,12-0, ,252 4,315 Page 50

51 Naproxen, level 2 Assigned value X [µg/l] (mean): 0,191 Standard deviation for Proficiency Assessment (0,25 * X) = 0,048 Conc. in spiked sample [µg/l] = 0, ,106-1, ,184-0, ,15-0, ,208 0, ,15-0, ,216 0, ,159-0, ,217 0, ,17-0, ,222 0, ,172-0, ,228 0, ,177-0, ,307 2, ,177-0, ,493 6, ,179-0,256 Page 51

52 Naproxen, level 3 Assigned value X [µg/l] (mean): 0,182 Standard deviation for Proficiency Assessment (0,25 * X) = 0,046 Conc. in spiked sample [µg/l] = 0, ,112-1, ,18-0, ,122-1, ,181-0, ,123-1, ,191 0, ,129-1, ,195 0, ,15-0, ,2 0, ,152-0, ,201 0, ,167-0, ,211 0, ,172-0, ,228 1, ,174-0, ,251 1, ,178-0, ,297 2, ,179-0, ,309 2,799 Page 52

53 Naproxen, level 4 Assigned value X [µg/l] (mean): 0,327 Standard deviation for Proficiency Assessment (0,25 * X) = 0,082 Conc. in spiked sample [µg/l] = 0, ,197-1, ,336 0, ,233-1, ,341 0, ,27-0, ,343 0, ,281-0,56 5 0,343 0, ,292-0, ,374 0, ,294-0, ,374 0, ,3-0, ,375 0, ,31-0, ,381 0, ,316-0, ,389 0, ,329 0, ,469 1,742 Page 53

54 Sulfamethoxazole, level 1 Assigned value X [µg/l] (mean): 0,158 Standard deviation for Proficiency Assessment (0,25 * X) = 0,040 Conc. in spiked sample [µg/l] = 0, ,074-2,13 6 0,161 0, ,123-0, ,166 0, ,126-0, ,166 0, ,138-0, ,175 0, ,14-0, ,176 0, ,142-0, ,178 0, ,147-0, ,178 0, ,148-0, ,185 0, ,153-0, ,189 0, ,157-0, ,272 2, ,16 0,043 Page 54

55 Sulfamethoxazole, level 2 Assigned value X [µg/l] (mean): 0,312 Standard deviation for Proficiency Assessment (0,25 * X) = 0,078 Conc. in spiked sample [µg/l] = 0, ,07-3, ,325 0, ,129-2, ,328 0, ,236-0, ,333 0, ,258-0, ,334 0, ,283-0, ,345 0, ,298-0, ,359 0, ,301-0, ,363 0, ,303-0, ,38 0, ,313 0, ,383 0, ,322 0,13 Page 55

56 Sulfamethoxazole, level 3 Assigned value X [µg/l] (mean): 0,268 Standard deviation for Proficiency Assessment (0,25 * X) = 0,089 Conc. in spiked sample [µg/l] = 0, ,145-1, ,28 0, ,153-1, ,285 0, ,161-1, ,295 0, ,211-0, ,296 0, ,217-0, ,298 0, ,218-0, ,306 0, ,24-0, ,317 0, ,244-0, ,324 0, ,26-0, ,335 1, ,267-0, ,338 1, ,268 0, ,368 1, ,271 0,051 Page 56

57 Sulfamethoxazole, level 4 Assigned value X [µg/l] (mean): 0,409 Standard deviation for Proficiency Assessment (0,25 * X) = 0,102 Conc. in spiked sample [µg/l] = 0, ,1-3, ,416 0, ,198-2, ,428 0, ,249-1, ,435 0, ,308-0, ,436 0, ,343-0, ,446 0, ,376-0, ,453 0, ,389-0, ,46 0, ,393-0, ,475 0, ,4-0, ,51 0, ,4-0, ,553 1, ,407-0, ,631 2, ,414 0,044 Page 57

58 Annexes Method specific evaluation Page 58

59 Comparison of methods Bisoprolol Number of Z-Scores Number of Methods Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 labs LCMSMS/enr LCMSMS/dir. inj Summe 18 Carbamazepine Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS /w. enr LCMSMS /dir.inj Sum 25 Page 59

60 Clenbuterol Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/ enrich LCMSMS/dir.inj Sum 20 Diazepam Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj Sum 18 Page 60

61 Diclofenac Number of Z-Scores Number of Methods Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 labs LCMSMS/enrich LCMSMS/dir.inj Sum 25 Gemfibrozil Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj Sum 17 Page 61

62 Ibuprofen Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj GCMS Sum 26 Iopamidol Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj Sum 25 Page 62

63 Iopromide Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj Sum 26 Naproxen Number of Z-Scores Number of Methods Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 labs LCMSMS/enrich LCMSMS/dir.inj GCMS Summe 21 Page 63

64 Sulfamethoxazole Methods Number of Z-Scores Z>-2 Z= Z=-1-+1 Z=+1-+2 Z>+2 Number of labs LCMSMS/enrich LCMSMS/dir.inj Sum 25 Almost all comparisons show that the different analytical techniques used (HPLC/MSMS with enrichment / direct injection) commonly do not produce significant different results. Iopromide, however, seems to be an exemption. The z-scores obtained using enrichment procedures are spread over the whole region of z-scores. An explanation for that result cannot be given and would need further investigations. Page 64

65 Method Comparison - Assigned values Level 1 Parameter Number of labs Assigned value HPLC/MSMS/ enrichm. [µg/l] Number of labs Assigned value HPLC/MSMS/ dir.inj.[µg/l] Number of labs Assigned value GCMS [µg/l] Conc. in spiked sample [µg/l] Bisoprolol 4 0, ,692 0,644 Carbamazepine 10 0, ,221 0,235 Clenbuterol 5 0, ,268 0,257 Diazepam 4 0, ,183 0,176 Diclofenac 10 0, ,495 0,442 Gemfibrozil 4 0, ,125 0,117 Ibuprofen 11 0, , ,396 0,369 Iopamidol 11 0, ,255 0,250 Iopromide 11 0, ,138 0,127 Naproxen 5 0, , ,148 0,111 Sulfamethoxazole 8 0, ,158 0,140 Page 65

66 Method Comparison assigned values Level 2 Parameter Number of labs Assigned value HPLC/MSMS/ enrichm. [µg/l] Number of labs Assigned value HPLC/MSMS/ dir.inj.[µg/l] Number of labs Assigned value GCMS [µg/l] Conc. in spiked sample [µg/l] Bisoprolol 4 0, ,209 0,184 Carbamazepine 7 0, , ,361 0,346 Clenbuterol 5 0, ,110 0,095 Diazepam 4 0, ,331 0,326 Diclofenac 7 0, , ,833 0,575 Gemfibrozil 4 0, , ,121 0,168 Ibuprofen 8 0, , ,116 0,102 Iopamidol 7 0, ,378 0,366 Iopromide 7 0, ,239 0,226 Naproxen 5 0, , ,168 0,186 Sulfamethoxazole 7 0, ,327 0,310 Page 66

67 Method Comparison assigned values Level 3 Parameter Number of labs Assigned value HPLC/MSMS/ enrichm. [µg/l] Number of labs Assigned value HPLC/MSMS/ dir.inj.[µg/l] Number of labs Assigned value GCMS [µg/l] Conc. in spiked sample [µg/l] Bisoprolol 4 0, ,223 0,201 Carbamazepine 7 0, , ,379 0,364 Clenbuterol 4 0, ,099 0,081 Diazepam 4 0, ,301 0,285 Diclofenac 8 0, , ,849 0,537 Gemfibrozil 4 0, , ,118 0,173 Ibuprofen 8 0, , ,140 0,110 Iopamidol 10 0, ,404 0,415 Iopromide 10 0, ,255 0,251 Naproxen 4 0, , ,167 0,178 Sulfamethoxazole 7 0, ,288 0,275 Page 67

68 Method Comparison assigned values Level 4 Parameter Number of labs Assigned value HPLC/MSMS/ enrichm. [µg/l] Number of labs Assigned value HPLC/MSMS/ dir.inj.[µg/l] Number of labs Assigned value GCMS [µg/l] Conc. in spiked sample [µg/l] Bisoprolol 3 0, ,357 0,420 Carbamazepine 7 0, , ,147 0,125 Clenbuterol 4 0, ,161 0,149 Diazepam 3 0, ,137 0,120 Diclofenac 8 0, , ,430 0,295 Gemfibrozil 3 0, , ,255 0,326 Ibuprofen 9 0, , ,327 0,268 Iopamidol 8 0, ,144 0,132 Iopromide 7 0, ,383 0,375 Naproxen 4 0, , ,254 0,346 Sulfamethoxazole 7 0, ,444 0,441 Page 68

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