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

Transcription

1 LACTIC ACID 9D /R6 LACTIC ACID This package insert contains information to run the Lactic Acid 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 Concentration Authorized Representative in the European Community Ingredients In vitro diagnostic medical device Batch code/lot number Reagent 1 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 March , 2009 Abbott Laboratories 1

2 NAME LACTIC ACID INTENDED USE The Lactic Acid assay is used for the quantitation of lactic acid in human plasma. SUMMARY AND EXPLANATION OF TEST Lactic acid, an intermediary in carbohydrate metabolism, is derived predominantly from skeletal muscle, brain, and erythrocytes. The blood lactate concentration is dependent on the rate of production and the rate of metabolism in the liver and kidneys. Approximately 30% of total lactate production is used by the liver. Moderate increase in lactate production results in increased hepatic lactate clearance, but uptake by the liver is saturable when concentrations exceed 2 mmol/l. For example, during strenuous exercise, lactate concentrations may increase significantly, from an average concentration of about 0.9 mmol/l to more than 20 mmol/l within 10 seconds. 1 The review by Stacpoole 2 describes the biochemistry and pathobiology of lactate metabolism. A pivotal characteristic of this metabolism is that lactate can only arise from reduction of pyruvate. Elevated lactate associated with reduced arterial ph is called lactic acidosis. Tissue hypoxia is the most common cause of lactic acidosis and is classified as Type A, while lactic acidosis that is nonhypoxic is classified as Type B. Under normal conditions, the concentration of lactate is about 10-fold higher than that of pyruvate. Shock is perhaps the most widely recognized cause of lactic acidosis; however, in some cases, excess lactate production may precede shock. Such conditions as myocardial infarction, severe congestive heart failure, pulmonary edema, and blood loss are common causes of shock associated with lactic acidosis. Other causes of lactic acidosis include intravenous infusion of substances such as fructose, sorbitol, or epinephrine, and large doses of drugs such as ethanol or acetaminophen. Hepatic necrosis, neoplasms, lymphomas, and various forms of leukemia have been reported to cause lactic acidosis. In diabetic coma, lactic acidosis is common. 3 PRINCIPLES OF PROCEDURE Lactic acid is converted to pyruvate and hydrogen peroxide (H 2 O 2 ) by lactate oxidase. Peroxidase catalyzes the oxidation of chromogen precursor by H 2 O 2 to produce a colored dye. The increase in absorbance at 548 nm is directly proportional to the lactic acid concentration in the sample. Methodology: Lactic Acid to Pyruvate REAGENTS Reagent Kit 9D89 Lactic Acid is supplied as a lyophilized, single reagent kit which contains: 10 x 10 ml Funnels (5) Bar code labeled cartridges (5) Estimated tests per kit: 393 Calculation is based on the minimum reagent fill volume per kit. Reactive Ingredients Concentration Lactate Oxidase 400 U/L Peroxidase (Horseradish) 2,400 U/L Chromogen precursors As required Inactive Ingredients: Contains buffer, fillers, and stabilizers. REAGENT HANDLING AND STORAGE Reagent Handling 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 Storage Unopened reagents are stable until the expiration date when stored at 2 to 8 C. Do not pool reagents. Reagent stability is 7 days if the reagent is uncapped and onboard. REAGENT HANDLING AND STORAGE (Continued) Instructions for Use 1. Remove the reagent caps from two bottles of. 2. Prepare the Working Reagent by adding 10 ml of sterile water to each of the two bottles. 10 ml H 2 O + R1 = 10 ml H 2 O + R1 = Working Reagent 1 3. Replace the reagent caps and mix each bottle by gentle inversion until completely dissolved. Do Not Shake. 4. Pour contents of both bottles into one of the empty bar code labeled cartridges provided with the reagent kit. Remove air bubbles, if present in the cartridge, with a new applicator stick. 5. Place the cartridge in Reagent Supply Center 1. 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 materials from different kit lot numbers. 4. 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. 4 Biosafey Level 2 5 or other appropriate biosafety practices 6,7 should be used for materials that contain or are suspected of containing infectious agents. 5. is classified per applicable European Community (EC) Directives as: Irritant (Xi). The following are the appropriate Risk (R) and Safety (S) phrases: R36/37/38 Irritating to eyes, respiratory system and skin. S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S35 This material and its container must be disposed of in a safe way. S46 If swallowed, seek medical advice immediately and show this container or label. SPECIMEN COLLECTION AND HANDLING Suitable Specimens Plasma is the acceptable specimen. Plasma: Use plasma collected by standard venipuncture techniques into glass or plastic tubes without gel barriers. The acceptable anticoagulant is sodium fluoride/potassium oxalate. Venous specimens should be obtained without the use of a tourniquet or immediately after the tourniquet has been applied. If there is any delay in obtaining the specimen, the tourniquet should be removed after the puncture has been performed, and the blood should be allowed to circulate for at least two minutes before sample is withdrawn. Patients should avoid exercise of the hand or arm immediately before and during the procedure. Centrifuge the specimen as soon after collection as possible and immediately remove the plasma from the red blood cells. 1 Ensure centrifugation is adequate to remove platelets. 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. Specimen Storage Plasma: Separated plasma may be analyzed immediately, stored at 2 to 8 C, or frozen. Samples are stable for 14 days at 2 to 8 C or up to 4 weeks at -20 C. Specimen stability was verified in an in-house study of 20 sodium fluoride/potassium oxalate plasma samples. NOTE: Stored specimens must be inspected for particulates. If present, mix and centrifuge the specimen to remove particulates prior to testing. 2

3 PROCEDURE Materials Provided 9D89 Lactic Acid Reagent Kit Materials Required but not Provided 1E75 Lactic Acid Calibrator 1 x 10 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. Plasma: Specimens with lactic acid values exceeding mg/dl (13.32 mmol/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 dilution of the specimen and automatically corrects the concentration by multiplying the result by the appropriate dilution factor. To set up the automatic dilution feature, refer to Section 2 of the instrument-specific operations manual for additional information. 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 Calibration is stable for approximately 7 days (168 hours). Calibration is required whenever a new reagent is reconstituted. Verify calibration curve 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. 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 Lactic Acid Calibrator package insert. QUALITY CONTROL The following process 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. Two levels of controls (normal and abnormal) 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 acceptable criteria following a change of reagent or calibrator lot. RESULTS 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 EXPECTED VALUES and SPECIFIC PERFORMANCE CHARACTERISTICS sections 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. The performance characteristics of Lactic Acid on an analyzer other than an ARCHITECT c Systems or the AEROSET System must be validated and verified. EXPECTED VALUES Reference Range Plasma 8 Range (mg/dl) Range (mmol/l) Venous 4.5 to to 2.2 To convert results from mg/dl to mmol/l, multiply mg/dl by A study was conducted using 204 plasma samples from 99 female and 105 male volunteers. Data were analyzed as described by Solberg 9 and Clinical and Laboratory Standards Institute (CLSI) protocol NCCLS C28-A. 10 From this study, 95% of male specimens fell within 5.0 to 19.4 mg/dl, with male samples ranging from 3.9 to 20.6 mg/dl. For female specimens, 95% fell within 4.7 to 16.8 mg/dl, with female samples ranging from 4.5 to 18.6 mg/dl. It is recommended that each laboratory determine its own reference range based upon its particular locale and population characteristics. SPECIFIC PERFORMANCE CHARACTERISTICS Linearity Lactic Acid is linear up to mg/dl (13.32 mmol/l). Linearity was verified using CLSI protocol NCCLS EP6-A. 11 Limit of Detection (LOD) The LOD for Lactic Acid is 0.05 mg/dl (0.006 mmol/l). The LOD is the mean concentration of an analyte-free sample + 2 SD, where SD = the pooled, within-run standard deviation of the analyte-free sample. Limit of Quantitation (LOQ) The LOQ for Lactic Acid is 0.18 mg/dl (0.020 mmol/l). The LOQ is the analyte concentration at which the CV = 20%. Interfering Substances Interference studies were conducted on the AEROSET System using CLSI protocol NCCLS EP7-P. 12 Interference effects were assessed by Dose Response and Paired Difference methods, at the medical decision level of the analyte. Interfering Substance Bilirubin Hemoglobin Human triglyceride Intralipid Interferent Concentration N Target Observed (mg/dl) (% of Target) 15 mg/dl (257 μmol/l) mg/dl (513 μmol/l) mg/dl (5.0 g/l) mg/dl (7.5 g/l) mg/dl (8.5 mmol/l) ,000 mg/dl (11.3 mmol/l) mg/dl (1.25 g/l) mg/dl (2.50 g/l) Bilirubin solutions at the above concentrations were prepared by addition of a bilirubin stock to human plasma pools. Hemoglobin solutions at the above concentrations were prepared by addition of hemolysate to human plasma pools. Human triglyceride solutions at the above concentrations were prepared by mixing an elevated triglyceride human plasma pool with a normal triglyceride human plasma pool. Intralipid solutions at the above concentrations were prepared by addition of Intralipid to human plasma pools. Interferences from medications or endogenous substances may affect results. 13 3

4 SPECIFIC PERFORMANCE CHARACTERISTICS (Continued) Precision The imprecision of the Lactic Acid assay is 6.3% Total CV. Representative data from studies using CLSI protocol NCCLS EP5-T2 14 are summarized below. Control Level 1 Level 2 N Mean (mg/dl) Within Run Between Run Between Day Total SD %CV SD %CV SD %CV SD %CV Method Comparison Correlation studies were performed using CLSI protocol NCCLS EP9-A. 15 Plasma results from the Lactic Acid assay on the AEROSET System were compared with those from a commercially available lactate oxidase methodology. Plasma results from the Lactic Acid assay on an ARCHITECT c System were compared with the Lactic Acid assay on the AEROSET System. AEROSET vs. Comparative Method ARCHITECT vs. AEROSET N Y - Intercept Correlation Coefficient Slope Range (mg/dl)* 6.2 to to *AEROSET Range BIBLIOGRAPHY 1. Burtis CA, Ashwood ER, editors. Tietz Textbook of Clinical Chemistry, 2nd ed. Philadelphia, PA: WB Saunders; 1994: Stacpoole PW. Lactic acidosis. In: Ober PK, editor. Endocrinology and Metabolism Clinics of North America. Philadelphia, PA: WB Saunders; 1993: 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 , Bloodborne Pathogens. 5. 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, 3rd ed. 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, Tietz NW, editor. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia, PA: WB Saunders; 1995: Solberg HE. Establishment and use of reference values. In: Burtis CA, Ashwood ER, editors. Tietz Textbook of Clinical Chemistry, 2nd ed. Philadelphia, PA: WB Saunders; 1994: Sasse EA, Aziz KJ, Harris EK, et al. How to Define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline (C28-A). Villanova, PA: The National Committee for Clinical Laboratory Standards, Tholen DW, Kroll M, Astles JR, et al. Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (EP6-A). 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, Young DS. Effects of Drugs on Clinical Laboratory Tests, 4th ed. Washington, DC: AACC Press; 1995: Kennedy JW, Carey RN, Coolen RB, et al. Evaluation of Precision Performance of Clinical Chemistry Devices Second Edition; Tentative Guideline (EP5-T2). Villanova, 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, TRADEMARKS The ARCHITECT c System family of instruments consists of c 4000, c 8000, and c instruments. AEROSET, ARCHITECT, c 4000, c 8000, c 16000, and c System are trademarks of Abbott Laboratories. All other trademarks, brands, product names, and trade names are property of their respective companies. 4

5 ARCHITECT c SYSTEMS ASSAY PARAMETERS Lactic Acid Plasma Conventional and SI Units Configure assay parameters General General о Calibration о SmartWash о Results о Interpretation Assay: Lact Type: Photometric Version: Number: 1050 Reaction definition о Reagent / Sample о Validity checks Reaction mode: End up Primary Secondary Read times Wavelength: 548 / 700 Main: Last required read: 25 Absorbance range: Sample blank type: None Color correction: о Reaction definition Reagent / Sample о Validity checks R1 Reagent: LACT0 Reagent volume: 200 Diluent: Saline Water volume: Diluent dispense mode: Type 0 Dispense mode: Type 0 Diluted Default Dilution name Sample sample Diluent Water Dilution factor dilution STANDARD 2.0 = 1:1.00 : = о : = о о Reaction definition о Reagent / Sample Validity checks Reaction check: None Maximum absorbance variation: Configure assay parameters Calibration о General Calibration о SmartWash о Results о Interpretation Assay: Lact Calibration method: Linear Calibrators о Volumes о Intervals о Validity checks Calibrator set: Calibrator level: Concentration: Lactic Blank: Water 0 Cal 1: Lactic1 Replicates: 3 [Range 1 3] о Calibrators Volumes о Intervals о Validity checks Calibrator: Lactic Diluted Calibrator level Sample sample Diluent Water Blank: Water 2.0 Cal 1: Lactic1 2.0 о Calibrators о Volumes Intervals о Validity checks Calibration intervals: Full interval: 168 (hours) Calibration type: Adjust type: None 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 Configure assay parameters SmartWash о General о Calibration SmartWash о Results о Interpretation Assay: Lact COMPONENT REAGENT / ASSAY WASH Volume Replicates Cuvette Trig 10% Detergent B 345 Lactic Acid Plasma Conventional Units Configure assay parameters Results Conventional Units о General о Calibration о SmartWash Results о Interpretation Assay: Lact Assay number: 1050 Dilution default range: Result units: mg/dl Low-Linearity: 0.2 High-Linearity: Gender and age specific ranges: GENDER AGE (UNITS) NORMAL EXTREME Either (Y) Configure result units Conventional Units Assay: Lact Version: Result units: mg/dl Decimal places: 1 [Range 0 4] Correlation factor: Intercept: Lactic Acid Plasma SI Units Configure assay parameters Results SI Units о General о Calibration о SmartWash Results о Interpretation Assay: Lact Assay number: 1050 Dilution default range: Result units: mmol/l Low-Linearity: 0.02 High-Linearity: Gender and age specific ranges: GENDER AGE (UNITS) NORMAL EXTREME Either (Y) Configure result units SI Units Assay: Lact Version: Result units: mmol/l Decimal places: 2 [Range 0 4] Correlation factor: Intercept: Due to differences in instrument systems and unit configurations, version numbers may vary. Displays the number of decimal places defined in the decimal places parameter field. Refer to the concentration specified on calibrator labeling or value sheet. In ARCHITECT software version 5.00 and above, these values are defined on the Configure calibrator set screen. The linear low value (Low-Linearity) is LOQ rounded up to the number of decimal places defined in the decimal places parameter field. 5

6 AEROSET SYSTEM ASSAY PARAMETERS Lactic Acid Plasma Conventional Units Assay Configuration: Outline Page Assay Name Assay # Line Lact 50 A-Line Quantitative Ranges Min Text Min Panic-L L-Reference-H Panic-H Max Max Text * 0.0* * * 0.2** L-Linear Range-H Reference Ranges* Age Male Female Qualitative Ranges N/A Lactic Acid Plasma SI Units Assay Configuration: Outline Page Assay Name Assay # Line Lact 50 A-Line Quantitative Ranges Min Text Min Panic-L L-Reference-H Panic-H Max Max Text * 0.0* * * 0.02** L-Linear Range-H Reference Ranges* Age Male Female Qualitative Ranges N/A Assay Configuration: Base Page Reaction Mode Wavelength-Prim/Sec Read time-main/flex AbsMaxVar END UP 548 / / Sample Blank Test Blank Read Time Abs Window Abs Limits ( ) S.Vol DS.Vol D.Vol W.Vol Standard Rgt Name/Pos Dil Diluent: * Dil Type# 0 Rgt Name/Pos R.Vol W.Vol Type# Reagent 1 LACT011 * Reaction Check Read Time A/B Range Minimum 1 1 / Factor/Intercept Decimal Places Units 1.0 / mg/dl Assay Configuration: Base Page Reaction Mode Wavelength-Prim/Sec Read time-main/flex AbsMaxVar END UP 548 / / Sample Blank Test Blank Read Time Abs Window Abs Limits ( ) S.Vol DS.Vol D.Vol W.Vol Standard Rgt Name/Pos Dil Diluent: * Dil Type# 0 Rgt Name/Pos R.Vol W.Vol Type# Reagent 1 LACT011 * Reaction Check Read Time A/B Range Minimum 1 1 / Factor/Intercept Decimal Places Units 1.0 / mmol/l Assay Configuration: Calibration Page Calib Mode Interval (H) Linear 168 Blank/Calib Replicates Extrapolation % Span Span Abs Range 3 / 3 0 BLK Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range BLK Water C1 Lactic Cal Deviation C FAC Limit (%) 10 Assay Configuration: SmartWash Page Rgt Probe Reagent Wash Vol Cuvette Assay Name Wash Vol Sample Probe Wash Assay Configuration: Calibration Page Calib Mode Interval (H) Linear 168 Blank/Calib Replicates Extrapolation % Span Span Abs Range 3 / 3 0 BLK Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range BLK Water C1 Lactic Cal Deviation C FAC Limit (%) 10 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. ** The linear low value (L-Linear Range) is LOQ rounded up to the number of decimal places defined in the decimal places parameter field. 6

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