This package insert contains information to run the Theophylline assay on the ARCHITECT c Systems and the AEROSET System.

Transcription

1 THEOPHYLLINE 1E /R4 THEOPHYLLINE This package insert contains information to run the Theophylline assay on the ARCHITECT c Systems and the AEROSET System. NOTE: Changes Highlighted NOTE: This package insert must be read carefully prior to product use. Package insert instructions must be followed accordingly. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. Customer Support United States: Canada: International: ABBOTT (English speaking customers) (French speaking customers) Call your local Abbott representative Symbols in Product Labeling Calibrator 1 Reagent 1 Calibrators 2 through 6 Reagent 2 Concentration Authorized Representative in the European Community Ingredients In vitro diagnostic medical device Batch code/lot number Catalog number/list number Serial number Consult instructions for use Manufacturer Temperature limitation Use by/expiration date ABBOTT LABORATORIES Abbott Park, IL 60064, USA ABBOTT Max-Planck-Ring Wiesbaden Germany July , 2007 Abbott Laboratories 1

2 NAME THEOPHYLLINE INTENDED USE The Theophylline assay is used for the quantitation of theophylline in human serum or plasma. SUMMARY AND EXPLANATION OF TEST The physiological effects of the antiasthmatic drug theophylline correlate better with the drug concentration in serum than with dosage. Since serious toxic effects of theophylline are related to the serum concentration and are not always preceded by minor adverse symptoms, serum theophylline monitoring helps to avoid adverse effects. 1-5 When theophylline is used to treat acute symptoms, monitoring serum concentration allows the physician to adjust the dosage regimen to compensate for interpatient variations in the theophylline elimination rate. 1 The chronic treatment of asthma and other bronchospastic diseases also requires individualization of the theophylline dosage to maintain serum concentrations within the therapeutic range. 2,3 A theophylline dosage generally can be maintained without further monitoring for 6 months in rapidly growing children and for 12 months in other patients. Changes in concurrent drug therapy, variations in drug elimination, or the appearance of side effects, uncontrolled symptoms, or altered drug clearance signal the need for measuring the serum theophylline concentration. 1,3 Methods historically used to monitor serum theophylline concentrations include gas-liquid chromatography, high-performance liquid chromatography (HPLC), and immunoassay. 1,5,6 PRINCIPLES OF PROCEDURE The Theophylline assay is a homogeneous enzyme immunoassay technique used for the analysis of theophylline in biological fluids. 7 The assay is based on competition for antibody binding sites between the analyte drug in the specimen and exogenous drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH). Since G6PDH activity decreases upon binding to the antibody, the concentration of drug in the specimen can be measured in terms of enzyme activity. Active G6PDH reduces nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay. Methodology: Enzyme Immunoassay REAGENTS Reagent Kit 1E09 Theophylline is supplied as a liquid, ready-to-use, two-reagent kit which contains: 2 x 38 ml 2 x 21 ml Estimated tests per kit: 408 Calculation is based on the minimum reagent fill volume per kit. Reactive Ingredients Concentration Mouse monoclonal antibodies to theophylline < 0.1% NAD > 15 mmol/l G6P < 38 mmol/l Sodium Azide < 0.1% Theophylline-G6PDH < 0.1% TRIS Buffer > 80 mmol/l Sodium Azide < 0.1% and also contain bovine serum albumin (BSA) as a stabilizer. REAGENT HANDLING AND STORAGE Reagent Handling Do not mix reagents from different kit lot numbers. When either the or the reagent cartridge becomes empty, replace both cartridges, calibrate, and validate the system by analyzing controls. Remove air bubbles, if present in the reagent cartridge, with a new applicator stick. Alternatively, allow the reagent to sit at the appropriate storage temperature to allow the bubbles to dissipate. To minimize volume depletion, do not use a transfer pipette to remove the bubbles. CAUTION: Reagent bubbles may interfere with proper detection of reagent level in the cartridge, causing insufficient reagent aspiration which could impact results. REAGENT HANDLING AND STORAGE (Continued) Reagent Storage Unopened reagents are stable until the expiration date when stored at 2 to 8 C. Do not freeze reagents or expose to temperatures above 32 C. Reagent stability is 28 days if the reagent is uncapped and onboard. WARNINGS AND PRECAUTIONS Precautions for Users 1. For in vitro diagnostic use. 2. Do not use components beyond the expiration date. 3. Do not mix reagents from different kit lot numbers. 4. Contains nonsterile mouse monoclonal antibodies. 5. CAUTION: This product requires the handling of human specimens. It is recommended that all human sourced materials be considered potentially infectious and be handled in accordance with the OSHA Standard on Bloodborne Pathogens. 8 Biosafety Level 2 9 or other appropriate biosafety practices 10,11 should be used for materials that contain or are suspected of containing infectious agents. For reagents not classified as dangerous per European Directive 1999/45/EC as amended, safety data sheet available for professional user on request. NOTE: Refer to Section 8 of the instrument-specific operations manual for proper handling and disposal of reagents containing sodium azide. SPECIMEN COLLECTION AND HANDLING Suitable Specimens Serum and plasma are acceptable specimens. Some gel separation tubes may not be suitable for use with therapeutic drug monitoring assays; refer to information provided by the tube manufacturer. 12 Serum: Use serum collected by standard venipuncture techniques into glass or plastic tubes with or without gel barriers. Ensure complete clot formation has taken place prior to centrifugation. When processing samples, separate serum from blood cells or gel according to the specimen collection tube manufacturer s instructions. Some specimens, especially those from patients receiving anticoagulant or thrombolytic therapy, may take longer to complete their clotting processes. Fibrin clots may subsequently form in these sera and the clots could cause erroneous test results. Plasma: Use plasma collected by standard venipuncture techniques into glass or plastic tubes. Acceptable anticoagulants are lithium heparin (with or without gel barrier), sodium heparin, potassium EDTA, sodium citrate, and sodium fluoride/potassium oxalate. Ensure centrifugation is adequate to remove platelets. When processing samples, separate plasma from blood cells or gel according to the specimen collection tube manufacturer s instructions. Some sample dilution may occur when samples are collected in tubes containing citrate anticoagulant. The amount of dilution and the possible need to correct for it should be considered when interpreting assay results for these samples. NOTE: Patient intake of caffeinated beverages does not need to be restricted. Pharmacokinetic factors influence the correct time of sample collection after the last drug dose. These factors include dosage form, mode of administration, concomitant drug therapy, and biological variations affecting drug disposition. 1-3,5,6 Refer to the drug manufacturer s package insert or the Physicians Desk Reference (PDR) for proper drug dosage and for theophylline measurement sampling times. For total sample volume requirements, refer to the instrument-specific ASSAY PARAMETERS section of this package insert and Section 5 of the instrument-specific operations manual. 2

3 SPECIMEN COLLECTION AND HANDLING (Continued) Specimen Storage Serum and plasma Temperature Maximum Storage 2 to 8 C 3 months 13, C 3 months 13 Bibliographic Reference Guder et al. 13 suggest storage of frozen specimens at -20 C for no longer than the time interval cited above. However, because temperatures of laboratory freezers may vary, establishing a range around -20 C for specimen storage may be necessary. This temperature range may be established from either the freezer manufacturer s specifications or your laboratory standard operating procedure(s) for specimen storage. NOTE: Stored specimens must be inspected for particulates. If present, mix and centrifuge the specimen to remove particulates prior to testing. PROCEDURE Materials Provided 1E09 Theophylline Reagent Kit Materials Required but not Provided 6E89 Theophylline Calibrator 1 x 5 ml 1 x 2 ml Control Material Saline (0.85% to 0.90% NaCl) for specimens that require dilution Assay Procedure For a detailed description of how to run an assay, refer to Section 5 of the instrument-specific operations manual. Specimen Dilution Procedures The ARCHITECT c Systems and the AEROSET System have automatic dilution features; refer to Section 2 of the instrument-specific operations manual for additional information. Serum and plasma: Specimens with theophylline values exceeding 40.0 μg/ml (222.0 μmol/l) are flagged and may be diluted using the Automated Dilution Protocol or the Manual Dilution Procedure. Automated Dilution Protocol If using the Automated Dilution Protocol, the system performs a 1:4 dilution of the specimen and automatically corrects the concentration by multiplying the result by the appropriate dilution factor. Manual Dilution Procedure Manual dilutions should be performed as follows: Use saline (0.85% to 0.90% NaCl) to dilute the sample. The operator must enter the dilution factor in the patient or control order screen. The system uses this dilution factor to automatically correct the concentration by multiplying the result by the entered factor. If the operator does not enter the dilution factor, the result must be multiplied by the appropriate dilution factor before reporting the result. NOTE: If a diluted sample result is flagged indicating it is less than the linear low limit, do not report the result. Rerun using an appropriate dilution. For detailed information on ordering dilutions, refer to Section 5 of the instrument-specific operations manual. CALIBRATION A Blank Adjustment (c Systems) or a Blank Calibration (AEROSET) using Theophylline Calibrator 1 is required once each day of assay use unless a full calibration is performed. Calibration is stable for approximately 14 days (336 hours). A full calibration is required with each reagent cartridge change and each change in reagent lot number. Verify the calibration with at least two levels of controls according to the established quality control requirements for your laboratory. If control results fall outside acceptable ranges, recalibration may be necessary. NOTE: Theophylline Calibrator 1 must be used as the blank. Do not use water to calibrate. Refer to the instrument-specific ASSAY PARAMETERS section of this package insert. For a detailed description of how to calibrate an assay, refer to Section 6 of the instrument-specific operations manual. For information on calibrator standardization, refer to the Theophylline Calibrator package insert. QUALITY CONTROL The following is the recommendation of Abbott Laboratories for quality control. As appropriate, refer to your laboratory standard operating procedure(s) and/or quality assurance plan for additional quality control requirements and potential corrective actions. A minimum of two levels of controls spanning the medical decision range are to be run every 24 hours. If more frequent control monitoring is required, follow the established quality control procedures for your laboratory. If quality control results do not meet the acceptance criteria defined by your laboratory, patient values may be suspect. Follow the established quality control procedures for your laboratory. Recalibration may be necessary. Review quality control results and acceptance criteria following a change of reagent or calibrator lot. RESULTS Factors that can influence the relationship between theophylline serum or plasma concentrations and clinical response include the type and severity of bronchial constriction, age, smoking, diet, general state of health, and use of other drugs. 2,3 The concentration of theophylline in serum or plasma depends on the time of the last drug dose; dosage form; mode of administration; concomitant drug therapy; sample condition; time of sample collection; and individual variations in absorption, distribution, biotransformation, and excretion. These parameters must be considered when interpreting results. 2-5 Refer to the instrument-specific operations manual for information on results calculations. ARCHITECT System Operations Manual Appendix C AEROSET System Operations Manual Appendix A Representative performance data are given in the SPECIFIC PERFORMANCE CHARACTERISTICS section of this package insert. Results obtained in individual laboratories may vary. LIMITATIONS OF THE PROCEDURE Refer to the SPECIMEN COLLECTION AND HANDLING and SPECIFIC PERFORMANCE CHARACTERISTICS sections of this package insert. EXPECTED VALUES Serum/Plasma The Theophylline assay accurately quantitates theophylline concentrations in human serum or plasma containing up to 40 μg/ml (222.0 μmol/l). In most patients, theophylline serum concentrations of 10 to 20 μg/ml (55.5 to μmol/l) effectively suppress chronic asthmatic and other bronchospastic symptoms. 2-5 Serum concentrations of 5 to 10 μg/ml (27.8 to 55.5 μmol/l) theophylline reportedly control apneic spells in neonates without causing apparent side effects. 2-4 Peak concentrations above 20 μg/ml (111.0 μmol/l) are often associated with toxicity. 2-5 NOTE: To convert results from μg/ml to μmol/l, multiply μg/ml by For effective treatment, some patients may require serum levels outside these ranges. Therefore, the expected range is provided only as a guide, and individual patient results should be interpreted in light of other clinical signs and symptoms (refer to the RESULTS section of this package insert). 3

4 SPECIFIC PERFORMANCE CHARACTERISTICS Specificity The Theophylline assay measures the total (protein-bound plus unbound) theophylline concentration in serum or plasma. Compounds whose chemical structure or concurrent therapeutic use would suggest possible cross-reactivity have been tested. Levels tested were at or above maximum physiological or pharmacological concentrations. The compounds listed in the table below caused 10% change in drug concentration when tested in the presence of 10 μg/ml theophylline. Compound Conc. Tested (μg/ml) Compound Conc. Tested (μg/ml) 8-Chlorotheophylline 60 7-Methylxanthine 100 1,3-Dimethyluric acid 100 Paraxanthine 50 Dyphylline 100 Phenobarbital 100 Ephedrine 5 Theobromine 100 Hypoxanthine 100 1,3,7-Trimethyluric acid Methyluric acid 200 Urea 1,000 1-Methylxanthine 40 Uric acid Methylxanthine 100 Xanthine 100 NOTE: The compound 1-methyluric acid, at a level of 100 μg/ml, caused an 11% change in drug concentration when tested in the presence of 10 μg/ml theophylline. The compound caffeine, at a level of 100 μg/ml, caused a 29% change in drug concentration when tested in the presence of 10 μg/ml theophylline. An average cup of coffee or tea in the United States contains 40 to 100 mg caffeine. Oral ingestion of 120 mg of caffeine has been shown to produce average peak plasma concentrations of 3.0 μg/ml. 15 NOTE: The compound 3-isobutyl-1-methylxanthine interferes with this assay. The compound is not a naturally occurring xanthine or known metabolite, but some laboratories use it as an internal standard in chromatographic procedures. 16 Reportable Range The reportable range (analytical measurement range) for Theophylline is 0.5 to 40.0 μg/ml (2.8 to μmol/l). Linearity was verified using a modified Clinical and Laboratory Standards Institute (CLSI) protocol NCCLS EP6-P2. 17 A study performed on the ARCHITECT c Systems and AEROSET System demonstrated linearity within ± 10% or 0.6 μg/ml (3.3 μmol/l) across the reportable range of the assay. Recovery Acceptable recovery is ± 10% or within 0.6 μg/ml of target concentration across the reportable range of the assay. Known concentrations of theophylline were added to human serum. Each sample was analyzed in replicates of four using the Theophylline assay. The resulting Percent (%) Recovery was calculated according to the following equation: %Recovery = (Mean / Target Concentration) 100 Delta = Mean Target Concentration Target Concentration (μg/ml) Mean (μg/ml) Delta (μg/ml) Percent (%) Recovery Average 105 The average recovery for the Theophylline assay was 105%, with individual spiked recoveries ranging from 99% to 117% of target concentrations. Limit of Quantitation (LOQ) The LOQ for Theophylline is 0.5 μg/ml (2.8 μmol/l). The LOQ is the analyte concentration at which the CV = 20%. Performance studies produced an LOQ of 0.4 μg/ml (2.2 μmol/l). Interfering Substances Interference studies were conducted using a modified CLSI protocol NCCLS EP7-P. 18 Interference effects were assessed by Dose Response and Paired Difference methods. Interfering Substance Interferent Concentration N Target Observed (μg/ml) (% of Target) Bilirubin 45 mg/dl (770 μmol/l) mg/dl (1,026 μmol/l) Hemoglobin 600 mg/dl (6 g/l) mg/dl (8 g/l) Intralipid 1,000 mg/dl (11.3 mmol/l) ,250 mg/dl (14.1 mmol/l) Human serum 7.5 g/dl (75 g/l) albumin IgG 12 g/dl (120 g/l) Bilirubin solutions at the above concentrations were prepared by addition of a bilirubin stock to human serum pools. Hemoglobin solutions at the above concentrations were prepared by addition of hemolysate to human serum pools. Intralipid solutions at the above concentrations were prepared by addition of Intralipid to human serum pools. Protein solutions at the above concentrations were prepared by addition of human serum albumin and IgG to human serum pools. Precision The imprecision of the Theophylline assay is 8% Total CV. Representative data from studies using CLSI protocol NCCLS EP5-A 19 are summarized below. Control Level 1 Level 2 Level 3 N Mean (μg/ml) Within Run SD %CV Between Run SD %CV Between Day SD %CV Total SD %CV Method Comparison Correlation studies were performed using a modified CLSI protocol NCCLS EP9-A. 20 Results from the Theophylline assay on the AEROSET System were compared with those from a commercially available enzyme immunoassay (EIA) and fluorescent polarization (FPIA) methodology. Serum and plasma results from the Theophylline assay on an ARCHITECT c System were compared with the Theophylline assay on the AEROSET System. AEROSET vs. EIA AEROSET vs. FPIA ARCHITECT vs. AEROSET N Y - Intercept Correlation Coefficient Slope Range (μg/ml)* 2.6 to to to 39.4 N %Bias at MDL** %Total Error at MDL** * AEROSET Range ** MDL = Medical decision level. %Bias and %Total Error were calculated using a modified CLSI protocol NCCLS EP21-A. 21 Calculations were performed using samples with concentrations between the medical decision levels of 10 and 20 μg/ml (55.5 and μmol/l). %Bias is calculated using least squares regression. %Total Error = %Bias + 2 SD of %Bias. 4

5 BIBLIOGRAPHY 1. Hendeles L, Weinberger M, Johnson G. Monitoring serum theophylline levels. Clin Pharmacokinet 1978;3(4): Hendeles L, Weinberger M. Theophylline: therapeutic use and serum concentration monitoring. In: Taylor WJ, Finn AL, editors. Individualizing Drug Therapy: Practical Applications of Drug Monitoring. New York, NY: Gross, Townsend, Frank; 1981:Vol 1, Hendeles L, Massanari M, Weinberger M. Theophylline. In: Middleton E Jr, Reed CE, Ellis EF, et al., editors. Allergy: Principles and Practice, 3rd ed. St Louis, MO: CV Mosby; 1988:Vol 1, Bierman CW, Williams PV. Therapeutic monitoring of theophylline: rationale and current status. Clin Pharmacokinet 1989;17(6): Glynn-Barnhart A, Hill M, Szefler SJ. Sustained release theophylline preparations: practical recommendations for prescribing and therapeutic drug monitoring. Drugs 1988;35(6): Rainbow SJ, Dawson CM, Tickner TR. Non-extraction HPLC method for the simultaneous measurement of theophylline and caffeine in human serum. Ann Clin Biochem 1989;26: Pincus MR, Abraham NZ Jr. Toxicology and therapeutic drug monitoring. In: Henry JB, editor. Clinical Diagnosis and Management by Laboratory Methods, 19th ed. Philadelphia, PA: WB Saunders; 1996: US Department of Labor, Occupational Safety and Health Administration. 29 CFR Part Occupational Exposure to Bloodborne Pathogens. 9. US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office; January World Health Organization. Laboratory Biosafety Manual. Geneva: World Health Organization, Sewell DL, Bove KE, Callihan DR, et al. Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline Third Edition (M29-A3). Wayne, PA: Clinical and Laboratory Standards Institute, Dasgupta A, Dean R, Saldana S, et al. Absorption of therapeutic drugs by barrier gels in serum separator blood collection tubes: volume- and time-dependent reduction in total and free drug concentrations. Am J Clin Pathol 1994:101(4); Guder WG, da Fonseca-Wollheim F, Heil W, et al. The Quality of Diagnostic Samples. Darmstadt, Germany: GIT Verlag; 2001: US Pharmacopeial Convention, Inc. General notices. In: US Pharmacopeia National Formulary, 1995 ed (USP 23/NF 18). Rockville, MD: The US Pharmacopeial Convention, Inc; 1994: Baselt RC. Disposition of Toxic Drugs and Chemicals in Man, 5th ed. Foster City, CA: Chemical Toxicology Institute; 2000: Bailey DG, Davis HL, Johnson GE. Improved theophylline serum analysis by an appropriate internal standard for gas chromatography. J Chromatogr 1976;121(2): Tholen DW, Kroll M, Krouwer J, et al. Evaluation of the Linearity of Quantitative Analytical Methods; Proposed Guideline Second Edition (EP6-P2). Wayne, PA: The National Committee for Clinical Laboratory Standards, Powers DM, Boyd JC, Glick MR, et al. Interference Testing in Clinical Chemistry; Proposed Guideline (EP7-P). Villanova, PA: The National Committee for Clinical Laboratory Standards, Kennedy JW, Carey RN, Coolen RB, et al. Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline (EP5-A). Wayne, PA: The National Committee for Clinical Laboratory Standards, Kennedy JW, Carey RN, Coolen RB, et al. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (EP9-A). Wayne, PA: The National Committee for Clinical Laboratory Standards, Krouwer JS, Astles JR, Cooper WG, et al. Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline (EP21-A). Wayne, PA: The National Committee for Clinical Laboratory Standards, TRADEMARKS AEROSET and ARCHITECT are registered trademarks of Abbott Laboratories. c System is a trademark of Abbott Laboratories. All other trademarks, brands, product names, and trade names are the property of their respective companies. 5

6 ARCHITECT c SYSTEMS ASSAY PARAMETERS Theophylline Serum/Plasma Conventional and SI Units Configure assay parameters General General о Calibration о SmartWash о Results о Interpretation Assay: Theo Type: Photometric Version: Number: 1076 Reaction definition о Reagent / Sample о Validity checks Reaction mode: Rate up Primary Secondary Read times Wavelength: 340 / Main: Last required read: 31 Flex: Absorbance range: Color correction: Sample blank type: None о Reaction definition Reagent / Sample о Validity checks R1 R2 Reagent: THEO0 Reagent volume: Diluent: Saline Water volume: Diluent dispense mode: Type 0 Dispense mode: Type 0 Type 0 Diluted Default Dilution name Sample sample Diluent Water Dilution factor dilution STANDARD : 3.0 = 1:1.00 1:4 : = 1:4.00 о = о о Reaction definition о Reagent / Sample Validity checks Reaction check: None Rate linearity %: Configure assay parameters Calibration о General Calibration о SmartWash о Results о Interpretation Assay: Theo Calibration method: Spline Calibrators о Volumes о Intervals о Validity checks Calibrator set: Calibrator level: Concentration: THEO Blank: THEO1 0 Cal 1: THEO2 Replicates: 1 [Range 1 3] Cal 2: THEO3 Cal 3: THEO4 Cal 4: THEO5 Cal 5: THEO6 о Calibrators Volumes о Intervals о Validity checks Calibrator: THEO Diluted Calibrator level Sample sample Diluent Water Blank: THEO1 3.0 Cal 1: THEO2 3.0 Cal 2: THEO3 3.0 Cal 3: THEO4 3.0 Cal 4: THEO5 3.0 Cal 5: THEO6 3.0 о Calibrators о Volumes Intervals о Validity checks Calibration intervals: Full interval: 336 (hours) Adjust interval: 24 (hours) Calibration type: Adjust type: Blank Default ordering type: Full Configure assay parameters SmartWash о General о Calibration SmartWash о Results о Interpretation Assay: Theo COMPONENT REAGENT / ASSAY WASH Volume Replicates Cuvette Trig 10% Detergent B*** 345 *** Select Detergent B for software versions prior to 2.2. Theophylline Serum/Plasma Conventional Units Configure assay parameters Results о General о Calibration о SmartWash Results о Interpretation Assay: Theo Result units: μg/ml Assay defaults: Low-Linearity: 0.5 High-Linearity: 40.0 Gender and age specific ranges: GENDER AGE (UNITS) NORMAL EXTREME Either (Y) Configure result units Assay: Theo Version: Result units: μg/ml Decimal places: 1 [Range 0 4] Correlation factor: Intercept: Theophylline Serum/Plasma SI Units Configure assay parameters Results о General о Calibration о SmartWash Results о Interpretation Assay: Theo Result units: μmol/l Assay defaults: Low-Linearity: 2.8 High-Linearity: Gender and age specific ranges: GENDER AGE (UNITS) NORMAL EXTREME Either (Y) Configure result units Assay: Theo Version: Result units: μmol/l Decimal places: 1 [Range 0 4] Correlation factor: Intercept: о Calibrators о Volumes о Intervals Validity checks Blank absorbance range: Span: Blank Blank Span absorbance range: Expected cal factor: 0.00 Expected cal factor tolerance %: 0 Due to differences in instrument systems and unit configurations, version numbers may vary. c 8000 Secondary Wavelength is 412 nm, c Secondary Wavelength is 416 nm. Displays the number of decimal places defined in the decimal places parameter field. Refer to concentration specified on the calibrator label or in the calibrator package insert. 6

7 AEROSET SYSTEM ASSAY PARAMETERS Theophylline Serum/Plasma Conventional Units Assay Configuration: Outline Page Assay Name Assay # Line Theo 76 A-Line Quantitative Ranges Min Text Min Panic-L L-Reference-H Panic-H Max Max Text * 0.0* * * 0.5 L-Linear Range-H 40.0 Reference Ranges N/A Theophylline Serum/Plasma SI Units Assay Configuration: Outline Page Assay Name Assay # Line Theo 76 A-Line Quantitative Ranges Min Text Min Panic-L L-Reference-H Panic-H Max Max Text * 0.0* * * 2.8 L-Linear Range-H Reference Ranges N/A Qualitative Ranges N/A Qualitative Ranges N/A Assay Configuration: Base Page Reaction Mode Wavelength-Prim/Sec Read time-main/flex Linearity % RATE UP 340 / / Sample Blank Test Blank Read Time Abs Window Abs Limits ( ) S.Vol DS.Vol D.Vol W.Vol Standard Rgt Name/Pos Dil Diluent: DILUENT C 10* Dil Type# 0 Rgt Name/Pos R.Vol W.Vol Type# Reagent 1 THEO051 * Reagent 2 THEO052 * Reaction Check Read Time A/B Range Minimum 1 1 / Factor/Intercept Decimal Places Units 1.0 / μg/ml Assay Configuration: Calibration Page Calib Mode Interval (H) Spline 336 Blank/Calib Replicates Extrapolation % Span Span Abs Range 1 / 1 1 BLK Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range BLK THEO C1 THEO Cal Deviation C2 THEO C3 THEO C4 THEO C5 THEO FAC Limit (%) C C C Assay Configuration: Base Page Reaction Mode Wavelength-Prim/Sec Read time-main/flex Linearity % RATE UP 340 / / Sample Blank Test Blank Read Time Abs Window Abs Limits ( ) S.Vol DS.Vol D.Vol W.Vol Standard Rgt Name/Pos Dil Diluent: DILUENT C 10* Dil Type# 0 Rgt Name/Pos R.Vol W.Vol Type# Reagent 1 THEO051 * Reagent 2 THEO052 * Reaction Check Read Time A/B Range Minimum 1 1 / Factor/Intercept Decimal Places Units 1.0 / μmol/l Assay Configuration: Calibration Page Calib Mode Interval (H) Spline 336 Blank/Calib Replicates Extrapolation % Span Span Abs Range 1 / 1 1 BLK Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range BLK THEO C1 THEO Cal Deviation C2 THEO C3 THEO C4 THEO C5 THEO FAC Limit (%) C C C Assay Configuration: SmartWash Page Rgt Probe Reagent Wash Vol Cuvette Assay Name Wash Vol Sample Probe Wash Assay Configuration: SmartWash Page Rgt Probe Reagent Wash Vol Cuvette Assay Name Wash Vol Sample Probe Wash Refer to Assay Configuration in Section 2 of the AEROSET System Operations Manual for information regarding assay parameters. * User defined or instrument defined. 7

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