Highly Sensitive Detection of Pharmaceuticals and Personal Care Products (PPCPs) in Water Using an Agilent 6495 Triple Quadrupole Mass Spectrometer

Transcription

1 Highly Sensitive Detect of Pharmaceuticals and Personal Care s (PPCPs) in Water Using an Agilent 6495 Triple Quadrupole Mass Spectrometer Applicat Note Authors Dan-Hui Dorothy Yang a, Mark A. Murphy b, and Sue Zhang a a Agilent Technologies Inc., 5301 Stevens Creek Blvd, Santa Clara, CA 95051, USA b EPA Reg 8 Lab, West 45 th Drive, Golden, CO 80403, USA Abstract This Applicat Note describes two methods to detect pharmaceuticals and personal care products (PPCPs) in water at part per trill (ppt) levels using the Agilent 6495 Triple Quadrupole Mass Spectrometer. The methods are divided into positive mode method and negative mode method since different mobile phases are required. The precise and accurate quantitat of 118 compounds with 316 MRM transits in positive mode, and 22 compounds with 62 MRM transits in negative mode were accomplished by dynamic multiple react monitoring (DMRM). The highly sensitive 6495 Triple Quadrupole LC/MS system was used to streamline the analysis by direct inject of 40 µl water samples without tedious analyte enrichment by solid phase extract (SPE).

2 Introduct Pharmaceuticals and Personal Care s (PPCPs) comprise a diverse collect of thousands of chemical substances, including prescript and over-the-counter therapeutic drugs, veterinary drugs, fragrances, and cosmetics. Several studies have shown that pharmaceuticals are present in our water supply systems 1,2. PPCPs in surface waters can eventually enter drinking water systems when treatments are insufficient. Governmental agencies, such as the EPA and European Water Framework, have proposed regulats to monitor water supply systems 3,4. PPCPs exist at low concentrats in drinking water, typically at part per trill (ppt) or ng/l levels. This poses significant analytical challenges. Sample enrichment by solid phase extract (SPE) is often necessary where detect is performed using low to mid-range triple quadrupole mass spectrometers 5. SPE requires large sample quantities, high consumpt of solvents, and laborious procedures. With the advent of the highly sensitive Agilent 6495 Triple Quadrupole Mass Spectrometer in combinat with the Agilent Jet Stream Ionizat Source for more efficient generat and sampling, we were able to investigate the occurrence and fate of PPCPs in water supply systems from source water to tap water by direct inject of water samples at low ppt levels. Improvements to the 6495 Triple Quadrupole include new front end optics for increased precursor transmiss, a newly designed curved and tapered collis cell for improved MS/MS spectral fidelity, and a new detector operating at dynode accelerating voltages of up to 20 kv. With this increased sensitivity, analytical workflow can be simplified and throughput can be increased. The extent of sample preparat includes filtering approximately 3 ml of sample, adding internal standards to a 1.0-mL aliquot of the filtered sample and injecting 40 µl of sample for analysis by LC/MS/MS with reporting limits for all analytes at 10 ppt. Limit of detect (LOD) and lower limit of quantitat (LLOQ) for most of the analytes are much lower than 10 ppt. Experimental Reagents and chemicals All reagents and solvents were of HPLC-MS grade. Acetonitrile was purchased from Honeywell (015-4). Ultrapure water was obtained from a Milli-Q Integral system equipped with LC-Pak Polisher and a 0.22-μm membrane point-of-use cartridge (Millipak). Ammonium acetate, 5 M solut, was purchased from Fluka ( ML). Acetic acid was purchased from Aldrich ( ML). The PPCP standards and some of the internal standards were acquired from an outside collaborator. The analytes and their internal standards as well as their MRM transits are listed in Table 1 for the positive mode method and Table 2 for the negative mode method, respectively. 2

3 Table 1. MRM transits of analytes and internal standards in positive mode method. Compound name (ev) ISTD (ev) 10,11-dihydro-10-hydroxycarbamazepine ,11-dihydro-10-hydroxycarbamazepine Acetylmorphine D6 6-Acetylmorphine Acetylmorphine D6 6-Acetylmorphine Acebutolol Acebutolol Acetaminophen D4 Acetaminophen Acetaminophen Albuterol Albuterol Amitriptyline D3 Amitriptyline Amitriptyline Amitriptyline metabolite Amitriptyline metabolite Amphetamine D5 Amphetamine Amphetamine Aripiprazole D8 Aripiprazole Aripiprazole Atenolol D7 Atenolol Atenolol Atorvastatin Atorvastatin Atrazine D5 Atrazine Atrazine D5 Atrazine Benzoylecgonine D3 Benzoylecgonine Benzoylecgonine Buprenorphine D4 Buprenorphine Buprenorphine Buprop Buprop Caffeine C3 Caffeine Caffeine Carbamazepine D10 Carbamazepine Carbamazepine D10 Carbamazepine Carbamazepine 10,11 epoxide Carbamazepine 10,11 epoxide Carisoprodol D7 Carisoprodol Carisoprodol D7 Carisoprodol Chlorpheniramine Chlorpheniramine Clenbuterol D9 Clenbuterol Clenbuterol Clopidogrel carboxylic acid Clopidogrel carboxylic acid Cocaethylene D3 Cocaethylene Cocaethylene Cocaine D3 Cocaine

4 Table 1. MRM transits of analytes and internal standards in positive mode method (continued). Compound name (ev) ISTD (ev) Cocaine Codeine D6 Codeine Codeine D6 Codeine Codeine Cotinine D3 Cotinine Cotinine D3 Cotinine DEET D6 DEET DEET D6 DEET Dehydroaripiprazole Dehydroaripiprazole Desmethylcitalopram D3 Desmethylcitalopram Desmethylcitalopram Desmethylvenlafaxine D6 Desmethylvenlafaxine Desmethylvenlafaxine Dextromethorphan D3 Dextromethorphan Dextromethorphan Diltiazem Diltiazem Diphenhydramine D3 Diphenhydramine Diphenhydramine Disopyramide Disopyramide Donepezil Donepezil Duloxetine D3 Duloxetine Duloxetine D3 Duloxetine Ecgonine methyl ester D3 Ecgonine methyl ester Ecgonine methyl ester EDDP D3 EDDP EDDP Erythromycin C2 Erythromycin Erythromycin Erythromycin-anhydro Erythromycin-anhydro Escitalopram Escitalopram Famotidine Famotidine Fentanyl D5 Fentanyl Fentanyl Fluoxetine D6 Fluoxetine Fluoxetine Fluticasone propate Fluticasone propate Gabapentin D10 Gabapentin Gabapentin Glyburide

5 Table 1. MRM transits of analytes and internal standards in positive mode method (continued). Compound name (ev) ISTD (ev) Glyburide Hydrocodone D6 Hydrocodone Hydrocodone Hydromorphone D3 Hydromorphone Hydromorphone Hydroxybuprop D6 Hydroxybuprop Hydroxybuprop Ketoprofen Ketoprofen Lamotrigine C- 15 N4 Lamotrigine Lamotrigine C3 Lamotrigine Levorphanol Levorphanol Lidocaine Lidocaine Loratadine Loratadine Lorazepam D4 Lorazepam Lorazepam MDA MDA MDEA MDEA MDMA D5 MDMA MDMA Mefenamic acid D3 Mefenamic acid Mefenamic acid D3 Mefenamic acid Meperidine D4 Meperidine Meperidine Meprobamate D7 Meprobamate Meprobamate Metformin Metformin Methadone D9 Methadone Methadone Methamphetamine D11 Methamphetamine Methotrexate D3 Methotrexate Methotrexate Methylphenidate D9 Methylphenidate Methylphenidate Metoprolol Metoprolol Mevastatin Mevastatin m-hydroxybenzoylecgonine m-hydroxybenzoylecgonine Modafinil D10 Modafinil

6 Table 1. MRM transits of analytes and internal standards in positive mode method (continued). Compound name (ev) ISTD (ev) Monoethylglycinexylidide Monoethylglycinexylidide Montelukast Montelukast Morphine D3 Morphine Morphine Nifedipine Nifedipine Nifedipine oxidized Nifedipine oxidized Norfentanyl D5 Norfentanyl Norfentanyl D5 Norfentanyl Norfluoxetine D6 Norfluoxetine Norfluoxetine D6 Norfluoxetine Normeperidine D4 Normeperidine Normeperidine Normeperidine Norquetiapine Norquetiapine Norsertraline C6 Norsertraline Norsertraline Norverapamil Norverapamil Omeprazole Omeprazole Oxazepam Oxazepam Oxcarbazepine Oxcarbazepine Oxycodone Oxycodone Oxymorphone D3 Oxymorphone Oxymorphone Oxymorphone glucuronide D3 Oxymorphone glucuronide Oxymorphone glucuronide Paroxetine D6 Paroxetine Paroxetine Phenmetrazine Phenmetrazine Phentermine D5 Phentermine Phenylpropanolamine D3 Phenylpropanolamine Phenylpropanolamine Pioglitazone Pioglitazone Pregabalin D6 Pregabalin Pregabalin Primidone

7 Table 1. MRM transits of analytes and internal standards in positive mode method (continued). Compound name (ev) ISTD (ev) Primidone Propranolol D7 Propranolol Propranolol Pseudoephedrine D3 Pseudoephedrine Pseudoephedrine Quetiapine D8 Quetiapine Quetiapine Ritalinic acid D10 Ritalinic acid Ritalinic acid Sertraline D3 Sertraline Sertraline Sildenafil Sildenafil Simvastatin Simvastatin Sotalol Sotalol Sulfamethazine C6 Sulfamethazine Sulfamethazine Sumatriptan Sumatriptan Tadalafil Tadalafil Temazepam D5 Temazepam Temazepam D5 Temazepam Thiabendazole C6 Thiabendazole Thiabendazole Tramadol C-D3 Tramadol Tramadol Trazadone D6 Trazadone Trazadone Triamterene Triamterene Trimethoprim C3 Trimethoprim Trimethoprim Tylosin Tylosin Valsartan Valsartan Venlafaxine D6 Venlafaxine Venlafaxine Verapamil Verapamil Zolpidem D7 Zolpidem Zolpidem Zolpidem phenyl-4-carboxylic acid Zolpidem phenyl-4-carboxylic acid

8 Table 2. MRM transits of analytes and internal standards in negative mode method. Name (ev) ISTD (ev) (±)11-nor-9-carboxy-delta-THC D9 (±)11-nor-9-carboxy-delta-THC (±)11-nor-9-carboxy-delta-THC Bezafibrate Bezafibrate Celecoxib Celecoxib Chloramphenicol D5 Chloramphenicol Chloramphenicol D5 Chloramphenicol Diclofenac D4 Diclofenac Diclofenac D4 Diclofenac Diclofenac 4-hydroxy C6 Diclofenac 4-hydroxy Diclofenac 4-hydroxy C6 Diclofenac 4-hydroxy Fenbufen Fenbufen Furosemide Furosemide Gemfibrozil D6 Gemfibrozil Gemfibrozil Hydrochlorothiazide Hydrochlorothiazide Ibuprofen C3 Ibuprofen Methylparaben C6 Methylparaben Methylparaben C6 Methylparaben Modafinil acid Modafinil acid Naproxen Naproxen n-butylparaben C6 n-butylparaben n-butylparaben C6 n-butylparaben Phenobarbital D5 Phenobarbital Phenobarbital Phenytoin D10 Phenytoin Phenytoin D10 Phenytoin Pravastatin Pravastatin Sulfamethoxazole C6 Sulfamethoxazole Sulfamethoxazole C6 Sulfamethoxazole Triclocarban C6 Triclocarban Triclocarban Triclosan C12 Triclosan Warfarin Warfarin

9 Instruments Agilent 1290 Infinity Binary Pump (G4220A) Agilent 1290 Infinity Standard Autosampler (G4226A) and sample cooler (G30B) Agilent 1290 Infinity Thermostatted Column Compartment (G16C) UHPLC condits are listed in Table 3 and Table 4 for positive mode method and negative mode method, respectively. Table 3. Agilent 1290 UHPLC condits for positive mode method. Parameter Value Column Agilent ZORBAX Eclipse Plus C18, mm, 1.8 µm (p/n ) Column temp 40 C Inject volume 40 µl Speed Draw 100 µl/min; Eject 100 µl/min Autosampler temperature 6 C Needle wash 5 seconds (80 % MeOH/20 % water) Mobile phase A) Water with 5 mm ammonium acetate % acetic acid B) Acetonitrile Flow rate 0.3 ml/min Gradient program Time B % Stop time 15 minutes Post time 1 minute Table 4. Agilent 1290 UHPLC condits for negative mode method. Parameter Value Column Agilent ZORBAX Eclipse Plus C18, mm, 1.8 µm (p/n ) Column temperature 40 C Inject volume 40 µl Speed Draw 100 µl/min; Eject 100 µl/min Autosampler temperature 6 C Needle wash 5 seconds (80 % MeOH/20 % water) Mobile phase A) Water with % acetic acid B) Acetonitrile Flow rate 0.3 ml/min Gradient program Time B % Stop time 10 minutes Post time 1 minute 9

10 MS detect Agilent 6495 Triple Quadrupole Mass Spectrometer with Agilent Jet Stream Electrospray Ionizat Source Agilent Jet Stream izat source parameters and Funnel RF voltages are critical for the sensitive detect of analytes. Agilent MassHunter B.07 Acquisit Software includes the MassHunter Source and ifunnel Optimizer Software that allows the users to get the best condits for analytes in an automated sequential fash. Applying all the optimized parameters obtained by optimizer software, including both the low-pressure and high-pressure funnel RF voltages, provided a significant increase in analyte responses 6. For multiple-analyte applicats, parameters are typically weighted towards hard-to-detect analytes. Mass spectrometer source condits generated by the Optimizer software are listed in Table 5 for the positive mode method and Table 6 for the negative mode method. Software Agilent MassHunter Data Acquisit Software, for triple quadruple mass spectrometer, Vers B Agilent MassHunter Qualitative Software, Vers B SP1 Agilent MassHunter Quantitative Software, Vers B.07.00/Build Table 5. Agilent 6495 Triple Quadrupole Mass Spectrometer source parameters for positive mode method. Parameter Value Ion mode Positive Drying gas temperature 250 Drying gas flow 16 Sheath gas temperature 400 Sheath gas flow 12 Nebulizer pressure 40 Capillary voltage 3,000 Nozzle voltage 0 Delta EMV 200 LPF RF 60 HPF RF 160 MS1 and MS2 resolut Unit Diluts Stock soluts for analyte standards and internal standards were prepared at 25 ppb in acetonitrile for each compound. All samples were fortified with internal standards at a constant concentrat of 250 ppt, while calibrat standards were spiked at 10 ppt, 25 ppt, 50 ppt, 100 ppt, 250 ppt, 500 ppt, and 1,000 ppt (7 levels) in MilliQ water. Two of the three unknown samples were from an outside collaborator. One was from a remote site removed from significant anthropogenic sources, and one was from an urban surface water source. Another sample was local drinking tap water (Santa Clara, USA). All unknown samples were fortified with internal standards at 250 ppt after filtrat. Table 6. Agilent 6495 Triple Quadrupole Mass Spectrometer source parameters for negative mode method. Parameter Value Ion mode Negative Drying gas temperature 200 Drying gas flow 12 Sheath gas temperature 400 Sheath gas flow 12 Nebulizer pressure 40 Capillary voltage 3,000 Nozzle voltage 2,000 Delta EMV 200 LPF RF 40 HPF RF 90 MS1 and MS2 resolut Unit 10

11 Results and Discuss Increased method performance The 6495 Triple Quadrupole LC/MS design enhancements provide an efficient transmiss 7. Figure 1 and Figure 2 show the responses of 118 analytes in positive mode, and 22 analytes in negative mode at 10 ppt. It is clearly demonstrated that most of the compounds can be detected at a concentrat much lower than 10 ppt without sample enrichment Counts Counts Acquisit time (min) Acquisit time (min) Figure 1. Signal response of the Agilent 6495 systems in positive mode (10 ppt at 40 µl direct inject) Ibuprofen Counts Acquisit time (min) Figure 2. Signal response of the Agilent 6495 systems in negative mode (10 ppt at 40 µl direct inject). 11

12 Calibrat curves Calibrat curves were assessed with PPCPs spiked in MilliQ water samples covering a concentrat range from 10 ppt to 1,000 ppt. Examples of the calibrat curves for metformin in positive mode and ibuprofen in negative mode are shown in Figure 3. The calibrat equats were generated using a quadratic fit with a weighting factor of 1/x including the origin. The correlat coefficients (R 2 ) for all target analytes in both polarities were greater than 0.99, and most were greater than 0.995, except for quetiapine in positive mode (R 2 = 0.982) due to an interfering systematic peak nearby. Precis and accuracy Triplicate injects were made for calibrat curves at each level. In most of the cases, the precis was very good. There were occasal cases in which accuracy was beyond the % range. Five to six very hydrophobic compounds, such as statin drugs, buprenorphine, and montelukast, had accuracy outliers at the low levels. This may be due to the HPLC vial surface absorpt of the compounds at lower spike levels. Overall, only 2.3 % of measurements had accuracy outliers beyond % (< 1 accuracy outlier per two compounds with 21 measurements per compound) if five outlier compounds were removed from accuracy considerat in positive mode. In negative mode, accuracy was excellent for all compounds except for celecoxib. The accuracy issue for celecoxib may be caused by the uneven HPLC vial surface adsorpt at low levels without a corresponding internal standard. Relative responses Responses Metformin - 7 Levels, 7 Levels Used, 21 Points, 21 Points Used, 0 QCs y = *x *x R 2 = A B ,000 Concentrat (pg/ml) Ibuprofen - 7 Levels, 7 Levels Used, 21 Points, 21 Points Used, 0 QCs y = E-007*x *x R 2 = ,000 Concentrat (pg/ml) Figure 3. Calibrat curves of metformin (positive) and ibuprofen (negative) in milliq water. Real-world samples Three samples were tested. The first was from local tap water (Santa Clara, USA). The other two samples were from an outside collaborator: one from a remote site removed from significant anthropogenic sources and the other from an urban surface water source. Duplicate injects were run on each sample. The compound was considered positive if the average concentrat of the two runs was greater than 10 ppt. The positive results are listed for these samples in Tables Figure 4 and Figure 5 show the chromatographs for the Santa Clara tap water and remote source water, respectively. Three compounds were detected above 10 ppt in each sample. 12

13 Table 7. Compounds found in local tap water with positive mode method. Name Inject 1 (ppt) Inject 2 (ppt) Average (ppt) Gabapentin Metformin Montelukast SCS Dwater (Gabapentin) *172.1 & 154.1, Area = 38, & 55.0, Area = 15, SCS Dwater (Metformin) 0.1 & 60.0, Area = 5, & 71.1, Area = 108, SCS Dwater (Montelukast) & 422.1, Area = 1, & 278.1, Area = 1, A B C Figure 4. Chromatographs of PPCPs found in local tap water (Santa Clara, CA) with positive method. Table 8. Compounds found in remote source sample with positive mode method. Name Inject 1 (ppt) Inject 2 (ppt) Average (ppt) Montelukast Caffeine DEET R8-01 (Caffeine) R8-01 (DEET) & 8.1, Area = 69, & 119.3, Area = 1,249, & 110.3, Area = 8, & 91.0, Area = 883, A 4.0 B 3.00 C R8-01 (Montelukast) & 422.1, Area = & 278.1, Area = Figure 5. Chromatographs of PPCPs found in remote source sample with positive mode method.

14 Table 9. Compounds found in an urban surface water sample with positive mode method. Name Inject 1 (ppt) Inject 2 (ppt) Average (ppt) 10,11-dihydro hydroxycarbamazepine Amitriptyline metabolite Amitriptyline Atenolol 2,599 2,212 2,405 Atorvastatin Atrazine Benzoylecgonine Buprop Caffeine 1,473 1,241 1,357 Carbamazepine 10,11 epoxide Carbamazepine Carisoprodol Clopidogrel carboxylic acid Cocaine Codeine Cotinine DEET Desmethylcitalopram Desmethylvenlafaxine Dextromethorphan Diltiazem Diphenhydramine Ecgonine methyl ester EDDP Erythromycin Erythromycin-anhydro Escitalopram Fluoxetine Gabapentin >>1,000 >>1,000 >>1,000 Hydrocodone Hydroxybuprop Ketoprofen Lamotrigine 868 1,0 940 Levorphanol Lidocaine Name Inject 1 (ppt) Inject 2 (ppt) Average (ppt) Loratadine Lorazepam Meprobamate Metformin 3,956 3,956 3,956 Methadone Methamphetamine Metoprolol Modafinil Monoethylglycinexylidide Montelukast Norquetiapine Norsertraline Oxazepam Oxcarbazepine Oxycodone Oxymorphone Phentermine Pregabalin Primidone Propranolol Pseudoephedrine Ritalinic acid Sertraline Sotalol Sulfamethazine Temazepam Thiabendazole Tramadol Trazadone Triamterene Trimethoprim Tylosin Valsartan Venlafaxine Verapamil Zolpidem phenyl-4-carboxylic acid

15 No compounds were found in the local tap water or the remote source water samples with negative mode method. The compounds found in the urban surface water sample in negative mode are listed in Table 10. Flexible reporting enabled by MassHunter Quantitative Analysis Software B.07 Instead of exporting results and averaging the replicates in excel, users can use the Fast PDF reporting system in Quant Analysis Software B.07 to generate the result in the desired format: averaging replicates, inserting preferred logo, and defining sample layout etc. The average of replicates can be accomplished by grouping the replicates under Sample Group. There are different choices of PDF report templates in the software product. Table 11 lists all of the relevant templates in Quant B07. Table 10. Compounds found in an urban surface water sample with negative mode method. Name Inject 1 (ppt) Inject 2 (ppt) Average (ppt) Celecoxib Chloramphenicol Diclofenac 4-hydroxy Diclofenac Furosemide Gemfibrozil Hydrochlorothiazide Ibuprofen Modafinil acid Naproxen Phenobarbital Phenytoin Pravastatin Sulfamethoxazole Triclocarban Triclosan Table 11. List of PDF report templates in Agilent MassHunter Quantitative Analysis B.07. DIR SUBDIR Catogory PDFTemplate PDF-Reporting Compliance AuditTrail.report.xml PDF-Reporting Enviromental Env_CC_Avg.report.xml PDF-Reporting Enviromental Env_CC_MidPoint.report.xml PDF-Reporting Enviromental Env_CC_Previous.report.xml PDF-Reporting Enviromental Env_DualGCResults.report.xml PDF-Reporting Enviromental Env_InitialCal.report.xml PDF-Reporting Enviromental Env_LCSSpike.report.xml PDF-Reporting Enviromental Env_MSD.report.xml PDF-Reporting Enviromental Env_QA_Check.report.xml PDF-Reporting Enviromental Env_Results.report.xml PDF-Reporting Enviromental Env_Results_withGraphics.report.xml PDF-Reporting Enviromental Env_TPH_Validat.report.xml PDF-Reporting General Gen_ByCompound.report.xml PDF-Reporting General Gen_BySample.report.xml PDF-Reporting General Gen_BySample_withSN.report.xml PDF-Reporting General Gen_Calibrat.report.xml PDF-Reporting General Gen_Complete.report.xml PDF-Reporting General Gen_ResultsSummary.report.xml PDF-Reporting General Gen_Samples.report.xml PDF-Reporting Special Pesticide_Residues.report.xml PDF-Reporting Special SIMScan.report.xml PDF-Reporting Special TargetedDeconvolut.report.xml PDF-Reporting Unknowns Unknowns all-hits.report.xml PDF-Reporting Unknowns Unknowns best-hits.report.xml 15

16 Figure 6 shows an example report of one sample in this study by the new PDF reporting generating system. The results of each sample can be arranged in separate pages or in the same page. Conclus Fast and simple LC/MS/MS methods for the accurate confirmat and quantitat of PPCPs in water have been developed. The methods leverage the full advantage of high sensitivity provided by the Agilent 6495 Triple Quadrupole Mass Spectrometer. It has been demonstrated that low ppt level LLOQs can be achieved for the quantitat of trace contaminants in water through direct inject. With these new design enhancements, tedious sample enrichment and cleanup processes can be avoided, which will increase sample throughput significantly. Flexible PDF reporting system can facilitate users to generate high quality report with many choices of formats and layouts. Batch name Sample name References D:\MassHunter\Data\091014_ESI+_Calibrat_Dorthy\QuantResults\Sue.batch.bin R Boyd, G. R; et al. Pharmaceuticals and Personal Care s (PPCPs) in Surface and Treated Waters of Louisiana, USA and Ontario, Canada. Science of The Total Environment, 311(1 3), pp Snyder, S. A; et al. Pharmaceuticals, Personal Care s, and Endocrine Disruptors in Water: Implicats for the Water Industry. Environmental Engineering Science 2003, 20(5), pp EPA Method 1694, Pharmaceuticals and Personal Care s in Water, Soil, Sediment, and Biosolids by HPLC/MS/MS; EPA-821-R , European Water Framework Directive 2000/60/EC; European Groundwater Directive 2006/118/EC. Quantitative Analysis Sample Report Compound Inject 1 Inject 2 Avg Caffeine DEET Montelukast Figure 6. Example report of one sample by PDF reporting system. 6. Cullum, N. Optimizing Detect of Steroids in Wastewater Using the Agilent 6490 Triple Quadrupole LC/MS System with ifunnel Technology, Agilent Technologies Applicat Note, publicat number EN 7. Yang, D. D; et al. Multi-Residue Pesticide Screening and Quantitat in Difficult Food Matrixes Using the Agilent 6495 Triple Quadrupole Mass Spectrometer, Agilent Technologies Applicat Note, publicat number EN. Acknowledgements The authors would like to thank Craig Marvin for initiating the project and coordinating the efforts. The authors would like to thank Ralph Hindle for insightful discusss on the method development and the result evaluat. 5. Ferra, I; Thurman, E. M; Zweigenbaum, J. Ultrasensitive EPA Method 1694 with Agilent 6460 LC/MS/MS with Jet Stream Technology for Pharmaceutical and Personal Care s in Water, Agilent Technologies Applicat Note, publicat number EN. This informat is subject to change without notice. Agilent Technologies, Inc., 2014 Published in the USA, December 23, EN