OASIS HLB Sample Extraction Products TM Setting New Standards for Solid-Phase Extraction (SPE) Technology • Simple and Fast Method Development • Enables High Throughput LC/MS/MS • Universal Sorbent • High and Consistent Recoveries • Batch-to-Batch Reproducibility Speed, Superior Results, Simplicity Sample preparation is no longer a bottleneck in lab productivity. Now SPE can outpace high throughput techniques such as LC/MS/MS. Waters designed the new Oasis™ HLB copolymer* with hydrophilic-lipophilic balance (HLB), unlike traditional SPE sorbents (Figure 1). Several major advantages for SPE result from our technology. Undesirable silanol activity, pH limitations, breakthrough of polar compounds, irreproducible and low recoveries, hydrophobic collapse and stopcock manipulation are now eliminated. For the first time, Oasis™ HLB sorbent enables high performance, robust, reversed-phase SPE in the 96-well extraction plate format. Oasis™ HLB sorbent makes automation of the 96-well format fast, simple, and rugged. Unique in its SAMPLE EXTRACTION PRODUCTS *patent pending ability to retain both non-polar and polar compounds and their metabolites, using a single, simple method — even if the bed runs dry, Oasis™ HLB sorbent truly sets the new standard for SPE. N O N-Vinylpyrrolidone Divinylbenzene Hydrophilic – Lipophilic Balance Optimal Properties for Reversed-Phase SPE Specific Surface Area: 810 m2/g Average Pore Diameter: 80 Å Total Pore Volume: 1.3 cm3/g Average Particle Diameter: 30 µm or 60 µm Figure 1 Unique Water-Wettable HLB Copolymer The Oasis™ HLB sorbent is a macroporous copolymer made from a balanced ratio of two monomers, the lipophilic divinylbenzene and the hydrophilic N-vinylpyrrolidone. Batch-to-Batch Reproducibility High and Consistent Recoveries Consistent and continued supply of Oasis™ HLB sorbent is assured because we manufacture it in Waters own ISO 9002-certified plant under the cGMP standard. Protocols for the synthesis and processing of Oasis™ HLB sorbent are specially designed and monitored for reproducibility. Unique, proprietary methods minimize fines content and render the sorbent extraordinarily clean. Each sorbent batch is checked again at final quality control by ten tests (Figure 2). A chromatographic selectivity test measures retention factors and relative retentions. Recoveries and relative standard deviations are reported for an actual SPE device test using a series of demanding analytes. As a result of careful process design and these stringent quality controls, a new standard has been set in batch-to-batch and lot-to-lot reproducibility for SPE methods (Figure 3a and 3b). Oasis™ HLB sorbent uniformity guarantees one SPE method for years to come. Oasis™ HLB sorbent provides excellent recovery, with no breakthrough and no undesirable secondary retention mechanisms. Very polar compounds may be readily isolated at consistent, high levels, even from pg/mL sample concentrations, with freedom from worry about the low recovery problems typical of C18 and other polymer sorbents (Figure 4a and 4b). Both a parent compound and its more polar metabolites can be recovered simultaneously with a single protocol. A major cause of poor recovery in SPE stems from the need to prewet traditional reversed-phase sorbents with a water-miscible organic solvent and keep them wetted — before applying the aqueous sample matrix. If the sorbent dries out before loading the sample, retention of the analytes falls sharply (Figure 5b). Then, capacity is severely compromised, and sample breakthrough can be significant. Since the Oasis™ HLB sorbent is water-wettable, it maintains its capability for higher retention and excellent recoveries of a wider spectrum of analytes (Figure 5a), even if the sorbent runs dry. This means that analysts with many samples to process no longer need to take extraordinary steps to keep sorbent beds from drying out during the critical steps prior to sample loading. Whether you are using 20 cartridges on a vacuum manifold or 96-well plates on automated equipment, the SPE process is greatly streamlined. In fact, with no means to monitor individual wells, the water wettability of Oasis™ HLB sorbent is essential to the reliable use of the 96-well plate format (Figure 6). Figure 2 A Certificate of Analysis in Each Box Product specifications, performance and sorbent batch test results are reported on a Certificate of Analysis (COA) that is included in every package. The COA details each test’s methodology and stringent specifications. Figure 3a and 3b Exceptional Batch-to-Batch Performance High recoveries of four compounds, ranging from the very polar to lipophilic neutral and basic compounds, are obtained using the conditions for the SPE batch test described on the COA. The recoveries for all compounds were highly consistent, with RSDs <4% for each analyte, using each of three different batches of Oasis™ HLB sorbent. Oasis™ HLB Extraction Cartridges (n=6) 100 2.02 3.66 1.21 2.40 % RSD 80 % Recovery 60 40 20 0 AcetaPropranolol Ranitidine minophen Dipropyl phthalate Oasis™ HLB Extraction Plates (n=96 wells) 100 0.64 1.48 1.39 2.59 % RSD 80 % Recovery 60 40 20 0 Aceta- Procainamide Doxepin Betamethasone minophen Valerate ■ Batch 1 ■ Batch 2 ■ Batch 3 Polar (acetaminophen), basic (doxepin, ranitidine) and non-polar, neutral (betamethasone valerate) drugs were extracted from saline, using the same method*. Care was taken to keep all silica-based and polymer sorbents, except Oasis™ HLB, wet throughout the extraction protocol, to avoid any loss of capacity due to surface drying. Recoveries were low on C18 and polymer SPE cartridges due to either breakthrough (acetaminophen) or excessive retention. Only the Oasis™ HLB extraction cartridge gave high recoveries for all drugs. *The protocol in Figure 7 was used except that the cartridges were equilibrated with 20 mM phosphate buffer. Analyses were performed by HPLC using Symmetry® columns. Recoveries shown are an average of 3 replicate extractions. ■ Acetaminophen ■ Doxepin ■ Betamethasone valerate 4a: C18-Bonded Silica 100 80 % Recovery Oasis™ HLB Sorbent Superior to C18-Bonded Silica (4a) and Other Polymers (4b) 60 40 20 0 C18 Glass Fiber Disk 3 cc/15 mg Oasis™ HLB C18 C18 PTFE Disk 3 cc/200 mg 3 cc/60 mg 3 cc/13 mg ■ Doxepin ■ Ranitidine ■ Betamethasone valerate 4b: Other Polymers 100 80 % Recovery Figure 4 60 40 20 0 Figure 5 Effect of Drying on Recovery — Oasis™ HLB versus C18 Sorbents 100 100 80 80 Procainamide Acetaminophen Ranitidine Propranolol Doxepin 60 40 Oasis™ HLB 3 cc/60 mg Figure 5b: C18 Cartridge % Recovery * Oasis™ HLB 1 cc/30 mg and 1 cc/100 mg C18 cartridges were conditioned on a Waters vacuum manifold. When the methanol reached the top of the upper frit in each cartridge, vacuum was maintained for different times to vary the cartridge drying time. The SPE protocol was then continued (see Figure 7). The data shown are the average of three replicate extractions. Figure 5a: Oasis™ HLB Cartridge % Recovery Even if Oasis™ HLB extraction cartridges run dry after being wet with methanol, high, reproducible recoveries are obtained from porcine serum samples spiked with representative pharmaceutical compounds (at right)*. Recovery of polar compounds, such as acetaminophen, from C18-bonded silica cartridges was adversely affected after less then one minute of drying*. Polymer B Polymer C Polymer A PS/DVB PS/DVB PS/DVB 3 cc/200 mg 3 cc/50 mg 3 cc/100 mg 20 60 40 20 0 0 0 5 Drying Time (minutes) 10 0 4 Drying Time (minutes) Figure 6 Oasis™ HLB Sorbent Enables High Performance SPE in 96-Well Plates Figure 6: 96-Well Plates 100 ≤ 35% ≤ 10% ≤ 2% RSD (n=96) 80 % Recovery Oasis™ HLB sorbent, in a single 96-well plate, gives high, reproducible recoveries for polar and basic drugs, with RSDs ≤2% (n=96) for each analyte extracted. Plates containing C18, in either packed bed or disk format, using the same protocol (Figure 7), showed low recoveries and high % RSDs. 60 40 20 0 C18 PTFE Disk C18 100 mg/well 14 mg/well Oasis™ HLB 30 mg/well ■ Procainamide ■ Ranitidine ■ Acetaminophen 8 Simple and Fast Method Development Sample preparation is required to maximize the quality of analytical results and to minimize the downtime of expensive, high-overhead analytical tools. Oasis™ HLB sorbent now makes it fast and easy to develop sample preparation methods that deliver high, reproducible recoveries. These methods are much more readily automated for high sample throughput than are traditional protocols such as liquidliquid extraction or protein precipitation (Figure 7). Unlike traditional C18-bonded silica sorbents, the Oasis™ HLB copolymer's reversed-phase adsorption mechanism Figure 8 Tetracyclines: A Simple, Fast, Effective SPE Method Tetracyclines are known to interact not only with surface silanols, but also with metals in silica-based sorbents. Oasis™ HLB copolymer is not complicated by either problem. Therefore, the generic method (Figure 7) gave high recoveries for the tetracyclines from acidified porcine serum*. In order to get high and consistent recoveries of tetracyclines with C18 cartridges, time-consuming method optimization is required. *HPLC analysis of the extracts was performed on a SymmetryShield™ RP8 column. Oasis™ HLB Cartridge 1 cc/30 mg (n=6) Compound C18 Cartridge 1 cc/100 mg (n=6) Concentration (µg/mL in serum) Recovery (%) RSD (%) Recovery (%) RSD (%) 2.5 94.8 1.4 40.7 0.82 2.5 104 0.55 67.4 0.44 Minocycline (CH 3)2N H HO O HO H N(CH 3)2 OH CONH 2 O O H Tetracycline HO HO CH 3 H N(CH 3)2 OH O O HO O H CONH 2 Figure 9 Figure 7 A Simple Generic SPE Protocol for Rapid Method Development Oasis™ HLB extraction products are versatile and easy to use. A single, simple protocol works for a wide range of acidic, basic, and neutral compounds, with recovery >85% and RSDs <5% (n=6) in all cases* (Figure 7). When required, a logical expansion of this protocol can be used to meet selectivity and sensitivity goals (Figures 10 and 11). *If required, serum may be acidified with phosphoric acid (20 µL/mL) to disrupt drug-protein binding. Achieve High Accuracy and Precision at Low ng/mL Levels PPD Pharmaco Validated Method for Analysis of Enalapril and Metabolite Enalaprilat in Human Plasma % Recovery n=6 Enalapril Interday Precision %CV n=6 Enalapril % Recovery n=6 Enalaprilat Interday Precision %CV n=6 Enalaprilat 0.5 ng/mL 110.9 3.6 103.6 3.0 5 ng/mL 112.2 4.3 109.4 3.2 80 ng/mL 107.0 1.6 104.5 1.2 Concentration of Enalaprilat & Enalapril Internal Std. 91.1 94.3 LOQ=0.25 ng/mL Solid-phase extraction on Oasis™ HLB extraction cartridges, 3 cc/60 mg, using the general SPE method (details confidential). LC/MS/MS Analysis General SPE Method Condition 1 mL Methanol ▼ Equilibrate 1 mL Water Column: Symmetry® C18 2.1 x 50, mm 3.5 µm Mobile Phase: Acetonitrile: water, 60:40 containing 0.5 g ammonium acetate and 1.5 mL acetic acid per liter Enalapril-d5 MB-IS 07 Sm (Mn, 1x1) 100 O ▼ Load 1 mL Spiked Sample ▼ Wash 1 mL 5% Methanol in Water ▼ Elute 1 mL Methanol ▼ Evaporate & Reconstititute 40 °C/200 µL Mobile Phase N H % MRM of 4 Channels ES + 395.50 > 238.90 HOOC O N O –11 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00 Time Enalaprilat-d5 MB-IS 07 Sm (Mn, 1x1) MRM of 4 Channels ES + 381.90 > 224.90 HOOC 100 HOOC N H % N O –14 0.25 0.50 0.75 1.00 1.25 1.50 Time 1.75 2.00 2.25 2.50 2.75 3.00 is uncomplicated by the often irreproducible population of surface silanols or metal impurities (Figure 8). This means acidic, basic, and neutral compounds, whether polar or non-polar, can be isolated reproducibly (RSDs <5%) with high recovery (>85%), using the same, simple SPE protocol. The generic scheme (Figure 7), which has proven useful for a wide variety of compound types may be the only protocol required, reducing method development time. The general protocol is especially suited to LC/MS/MS analysis since this analytical system simplifies method development by providing the required selectivity and sensitivity. PPD Pharmaco (Madison, WI) validated a simple method for enalapril and its metabolite enalaprilat using Oasis™ HLB cartridges and LC/MS/MS; they achieved high accuracy and precision at low ng/mL levels (Figure 9). Figure10 Optimized SPE Method Condition/Equilibrate 1 mL Methanol/1 mL Water ▼ Load 1 mL Spiked Sample ▼ Wash 1 1 mL 5% Methanol in Water Acidic Compounds ▼ Basic Compounds ▼ ▼ Wash 2 Acid in Methanol/Water Wash 2 Base in Methanol/Water ▼* ▼* Elute Base in Methanol/Water Elute Acid in Methanol/Water *Additional washes may be required Figure 11 Meeting the Background Challenge of UV Detectors: Analysis of Tricyclic-Antidepressants in Porcine Plasma 2 4 3 1 Generic SPE Method 5 Meet Selectivity and Sensitivity Goals Since the Oasis™ HLB sorbent is stable from pH 1 to 14 and unaffected by common organic solvents, you may take advantage of many more available options for method optimization (Figure 10). For some applications cleaner extracts are required to achieve higher selectivity and sensitivity with traditional ultraviolet or fluorescence detectors. Since retention by the Oasis™ HLB sorbent is very predictable, a cleaner extract can be achieved by simply manipulating the organic concentration and the pH (Figure 11). This procedure (Figure 10) allows compounds to be retained in a non-ionized or more lipophilic form in order to remove interferences with a higher concentration of organic solvent. The pH is then changed to allow the compound to be eluted in the charged or more hydrophilic state, without increasing the percent of organic solvent. 6 0.004 AU Sample Blank 0 2 1 4 2 6 minutes 4 3 Optimized SPE Method 5 6 0.004 AU Sample Blank 0 Column: Guard Column: Temperature: Mobile Phase: Detection: Flow Rate: Injection Volume: Plasma Extracts: Spiked at 500 ng/mL 2 4 6 minutes SymmetryShield™ RP8, 3.5 µm, 4.6 x 75 mm Sentry™ Guard Column SymmetryShield™ RP8, 5 µm 29 °C 50 mM phosphate, pH 7: methanol (33.6:66.4) UV at 254 nm 1.4 mL/min 140 µL (Generic Method) or 110 µL (Optimized Method) 1. Nordoxepin 2. Nortriptyline 3. Doxepin (IS) 4. Imipramine 5. Amitriptyline 6. Trimipramine Details of Optimized Method Wash 1: 2% ammonium hydroxide in 5% methanol Wash 2: 2% ammonium hydroxide in 65% methanol Wash 3: 2% acetic acid in 5% methanol Elute: 65% methanol in water or omit wash 3 and elute with 2% acetic acid in 65% methanol Universal Sorbent With Oasis™ HLB extraction cartridges and plates, you can isolate a wider range of acidic, basic and neutral compounds with one SPE sorbent, using a single, simple method. The Oasis™ HLB copolymer, designed for reversed-phase SPE, has proven to be the closest thing yet to a “universal” extraction sorbent. Excellent recoveries and reproducibilities are obtained for drugs and their metabolites from serum for a broad range of compounds using a simple extraction protocol (Figure 12). The universal sorbent simplifies the automation of high throughput LC/MS/MS methods with Oasis™ HLB extraction plates to an extraordinary degree. Figure 12 One Simple Procedure: Many Applications Shown are seventeen drugs with a wide range of polarity, grouped into acid, neutral and base categories. The samples were spiked at the indicated concentrations in porcine serum, then extracted with 1cc/30 mg Oasis™ HLB cartridges, using the same SPE method (Figure 7).* All recoveries, shown as the mean of six replicates, were >90% with RSDs <3.5%, independent of the nature of the compounds. *Serum was acidified with phosphoric acid (20 µL/mL) to disrupt drug-protein binding when necessary. HPLC analysis was performed on Symmetry® columns. % Recovery ■ Acids ■ Neutrals ■ Bases Ibuprofen Naproxen Salicylic Acid Sulfadiazine Sulfamerazine Acetaminophen Theobromine Paraxanthine Theophylline Caffeine High Capacity When transferring methods from a C18-bonded phase to Oasis™ HLB products, keep in mind the greater capacity of the HLB sorbent (Figure 13). A 100-200 mg C18 cartridge may be replaced by 30 mg of Oasis™ HLB sorbent; 200-500 mg of C18 may be replaced by 60 mg of Oasis™ HLB sorbent. Achieve Low Elution Volumes without Sacrificing Capacity The high capacity of the Oasis™ HLB sorbent made it easy to meet your request for plasma sample preparation with low elution volumes without sacrificing performance. Waters now offers the Oasis™ HLB 96-well solid-phase extraction plates Procainamide Ranitidine Oxycodone Propranolol Naltrexone Salbutamol Doxepin 0 20 40 60 80 100 Figure 13 Higher Retention Means Greater Capacity, No Breakthrough Capacity for a given analyte is a function of its retention factor (k) in a specified solvent,* as well as the surface area and pore structure of the sorbent. The density of Oasis™ HLB sorbent is about half that of a bonded-silica phase. So with equivalent bed volume, 2–3x more surface area, and a dramatic increase in k values, HLB sorbent has typically a 3-10x greater capacity than that of C18-bonded silica. *Data shown were obtained with two 3.9 x 150 mm columns, each packed with one of the sorbents, operated under the same conditions: mobile phase: 20 mM potassium phosphate, pH 7.0/methanol (95/5 v/v); temperature: 30 °C; flow rate: 1.0 mL/min; detection: UV @ 254 nm. Retention Factor (k) Comparison C18 Cartridge H O O HO O H N O H N H3 C N CH 3 Oasis™ HLB Cartridge Salicylic acid CH 3 N Theobromine N Acetaminophen OH HO O HO Catechol 0 50 100 with 10 mg of sorbent in each well. Since Oasis™ HLB sorbent has 3 to 10 times greater capacity than traditional silica-based sorbents or the newer disk-formatted plates, 10 mg of sorbent has all the capacity you’ll need for plasma sample preparation, even for highly polar drugs and metabolites. At elution volumes less than 150 µL, the Oasis™ HLB 10 mg/well extraction plate gives high (>85%) and reproducible recoveries (RSDs <10%) for all drugs and their metabolites. Because your drug and its metabolites are extracted in less than 150 µL of volume, you can eliminate the time consuming and tedious evaporation and reconstitution step from your SPE method. Just elute and shoot. This makes Oasis™ HLB products ideally suited for situations where high throughput SPE is a requirement (Figure 14). With Oasis™ HLB extraction plates you get high throughput with reliable and reproducible results fast enough to keep pace with your LC/MS/MS systems. Figure 14 Recovery Comparisons: Oasis™ HLB Plates (10 mg/well) versus Disk Formatted Plates Polar drugs (Procainamide, Acetaminophen, Theophylline) are extracted with significantly higher recoveries using the Oasis™ HLB extraction plate. Oasis™ HLB Plate (10 mg/well) Procainamide Acetaminophen Theophylline Dipropyl Phthalate C18 PTFE Disk Procainamide Acetaminophen Theophylline Dipropyl Phthalate 0 20 40 60 % Recovery 80 100 Competitive Comparison of Various Sorbents This table summarizes the experimental results displayed in Figure 4a and 4b. Sorbent Standard C18 Thin Disk C18 Polymer A PS/DVB Polymer B PS/DVB Polymer C PS/DVB Oasis™ HLB Good for Bases Good for Polars Universal Sorbent Low Swelling no yes* no no no yes no no yes yes no yes no no no no no yes yes yes no yes no yes * Recovery of doxepin is good only when a volume of methanol greater than 600 µL is used for elution (see Figure 4 for conditions). With smaller elution volumes typical for such a small quantity of sorbent, recovery is <50%, a result indicating the problematic interaction of bases with silanol groups. Ultrafast On-Line Analysis The Oasis™ HLB extraction column makes it possible to analyze a specific drug or metabolite in plasma or serum with an analysis time of 1.2 minutes per sample, using LC/MS/MS. The plasma sample can be directly injected onto the column. Direct determination of the drug or metabolite is made at concentrations in the range of 5-1000 ng/mL with an intra-assay accuracy of typically around 5% RSD. For more information request the Oasis™ HLB extraction column data sheet. Ordering Information Description Oasis Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ Oasis™ ™ HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB HLB Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Extraction Cartridge, 1 cc/30 mg Cartridge, 3 cc/60 mg Cartridge, 6 cc/200 mg Cartridge, 6 cc/500 mg LP* Cartridge, 12 cc/500 mg LP Cartridge, 20 cc/1 g LP Cartridge, 35 cc/6 g LP Column, 1 mm x 50 mm Column, 1 mm x 50 mm Plate, 30 mg/96-well Plate, 30 mg/96-well Plate, 30 mg/96-well Plate, 10 mg/96-well Plate, 10 mg/96-well Plate, 10 mg/96-well Quantity Part Number 100/box 100/box 30/box 30/box 20/box 20/box 10/box 1/box 10/box 1/pkg 3/pkg 9/pkg 1/pkg 3/pkg 9/pkg WAT094225 WAT094226 WAT106202 186000115 186000116 186000117 186000118 186000119 186000120 WAT058951 WAT058939 186000233 186000128 186000129 186000232 1/box 25/box 50/box 50/box 50/box 50/box 1/pkg 1/pkg WAT058941 WAT058942 WAT058943 WAT058957 WAT058958 WAT058959 WAT058955 WAT058956 WAT097944 *LP refers to 60 µm particle size. Accessories for Oasis™ HLB Extration Plate Extraction Plate Manifold Disposable Tray Reservoir Sample Collection Plate 350 µL Sample Collection Plate 1 mL Sample Collection Plate 2 mL Sealing Cap for Collection Plate Manifold Gasket, top Manifold Gasket, white Extraction Plate Manifold Kit A (includes extraction plate manifold, reservoir tray, manifold top gasket, sealing cap and 350 µL collection plate) Extraction Plate Manifold Kit B (includes extraction plate manifold, reservoir tray, manifold top gasket, sealing cap and 1 mL collection plate) Extraction Plate Manifold Kit C (includes extraction plate manifold, reservoir tray, manifold top gasket, sealing cap and 2 mL collection plate) Accessories for Oasis™ HLB Extration Cartridges Waters Extraction Manifold, 20 position Without rack, includes 20 needle tips, 25 plugs and ejector tool Complete with rack for 13 mm x 75 mm tubes) Complete with rack for 13 mm x 100 mm tubes) Complete with rack for 16 mm x 75 mm tubes) Complete with rack for 16 mm x 100 mm tubes) Vacuum Vacuum Vacuum Vacuum Pumps pump (110 V, 60 Hz) pump (220 V, 50 Hz) pump (110 V, 50 Hz) Visit us on the Internet: http://www.waters.com Sales Offices: Austria and Export (Central and South East Europe, CIS, Middle East, India and India Subcontinent) (43) 1 8771807 Australia (61) 2 9933 1777 Belgium and Luxembourg (02) 2 7261000 Brazil (55) 11 543 7788 Canada 800 252 4752, CIS 7 095 336 7000 Czech Republic (42) 02 617 11384 Denmark (45) 46 598080 Finland (358) 9 506 4140 France 01 30487200 Germany (49) 6196 40 06 00 Hong Kong (852) 2964 1800 Hungary (36) 1 270 5086 India (91) 80 8371900 Italy (02) 2 27421.1 Japan (81) 3 3471 7191 Malaysia (603) 704 8600 Mexico (525) 524 5414 The Netherlands (0) 76 508 7200 Norway (0) 638 46 050 Peoples Republic of China - (86) 10 65260828 Poland (48) 22 33 4400 Puerto Rico (787) 747 8445, 790 2225 Singapore (65) 339 3301 Spain (34) 933259616 Sweden (0) 8623 0090 Switzerland (41) 62 889 2030 Taiwan (886) 2 706 8766 UK and Ireland (44) 1 923 816700 All other countries: Waters Corporation U.S.A. 508 478 2000/800 252 4752 WAT097945 WAT097946 1/box WAT200677 1/box 1/box 1/box 1/box WAT200606 WAT200607 WAT200608 WAT200609 1/box 1/box 1/box WAT085114 WAT085115 WAT085123 The quality management system of Waters’ manufacturing facility, Taunton, Massachusetts, complies with the International Standard ISO 9002 Quality Management and Quality Assurance Standards. Waters’ quality management system is periodically audited by the registering body to ensure compliance. Waters, Oasis, Symmetry, and SymmetryShield are trademarks of Waters Corporation ©1998 Waters Corporation, 5/98, WB025-US
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