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en II U 3B29 34-5701/R10 Read Highlighted Changes Revised June 2010 Barbiturates II U

Customer Service: Contact your local representative or find country specific contact information on www.abbottdiagnostics.com

Package insert instructions must be carefully followed. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

Key to symbols used

List Number Expiration Date

For In Vitro Diagnostic Medical Device Calibrator (A-F)

Lot Number Control Low, Medium, High (L, M, H)

Store at 2‑8°C Reagent Pack

Reaction Vessels Store at 15-30°C

Sample Cups

Consult instructions for use Authorized Representative in the European Community

Manufacturer Contains Sodium Azide. Contact with acids liberates very toxic gas.

See REAGENTS section for a full explanation of symbols used in reagent component naming.

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3B29-1D-20_Eng_ReIn.indd 1 6/28/2010 12:27:51 PM

Color: Black LE: Pam DTP: Scott/Ania NAME *3B29-99 includes an AxSYM Barbiturates II U Reagent Pack (100 Tests) Barbiturates II U and reaction vessels (100 each). 3B29-20 includes these items for international shipments. INTENDED USE CALIBRATORS The AxSYM Barbiturates II U assay is a semi-quantitative reagent system for the detection of barbiturates in human urine. Measurements obtained XSYSTEMS Barbiturates II U Calibrators (9669-07) aid in the diagnosis and treatment of use or abuse. 6 Bottles (4 mL A, 2.5 mL each B-F) of XSYSTEMS Barbiturates II The AxSYM Barbiturates II U assay provides only a preliminary analytical U Calibrators. Calibrator A contains human urine and Calibrators B test result. A more specific alternate chemical method must be used in through F contain prepared in human urine to yield the order to obtain a confirmed analytical result. Gas chromatography/mass following concentrations: spectrometry (GC/MS) is the preferred confirmatory method.1 Clinical considerations and professional judgment should be applied to any Secobarbital drug of abuse test result, particularly when preliminary positive results Concentration Bottle (ng/mL) (µmol/L) are used. 0 0.00 SUMMARY AND EXPLANATION OF TEST 200 0.84 The AxSYM Barbiturates II U assay utilizes Fluorescence Polarization Immunoassay (FPIA) technology. Refer to the AxSYM System Operations 400 1.68 Manual, Section 3, under Principles of Operation for a discussion of 700 2.94 this technology. 1200 5.04 Barbiturates are central nervous system . They are used 2000 8.40 therapeutically as , , and .2 Although the legal availability of barbiturates has declined, they are frequently abused Preservative: Sodium Azide. sedatives or drugs.3-5 The most commonly abused barbiturates Abbott manufactures internal reference standards for Barbiturate II Urine are the short-acting compounds such as secobarbital, using Secobarbital (Purity greater than or equal to 98% by TLC). Barbiturate and . Tolerance to these drugs can develop from chronic II Urine calibrators are manufactured gravimetrically and tested against use and death may occur from either overdose or abrupt withdrawal of these internal reference standards. the drug.3,5 CONTROLS The Barbiturates II U assay is designed to perform at a variety of commonly used cut-off levels. The analyzer has been factory set at 200.00 ng/mL. XSYSTEMS Multiconstituent Controls (9687-12) Abbott Laboratories recommends the use of this cut-off, if appropriate for 2 Bottles each of Low, Medium, and High (4.5 mL each), prepared in human your client population. To configure your cut-off in your laboratory refer to urine diluent to read within the following ranges: the INSTRUMENT PROCEDURE section in this insert. Secobarbital Selection of the cut-off value should be based upon review of the laboratory’s and their clients’ needs, sensitivity of available confirmation Concentration Range methods and the sensitivity and cross-reactivity data of the assay itself. Bottle (ng/mL) (µmol/L) (ng/mL) (µmol/L) 300 1.26 194.55 - 405.45 0.82 - 1.70 BIOLOGICAL PRINCIPLES OF THE PROCEDURE 800 3.36 573.89 - 1026.11 2.41 - 4.31 The AxSYM Barbiturates II U assay is based on Fluorescence Polarization 1500 6.30 1085.03 - 1914.97 4.56 - 8.04 Immunoassay (FPIA) technology. The AxSYM Barbiturates II U Reagents and sample are pipetted in the following sequence: Preservative: Sodium Azide. SAMPLING CENTER OTHER REAGENTS • Sample and all AxSYM Barbiturates II U Reagents required for one test AxSYM Probe Cleaning Solution (9A35-05) are pipetted by the sampling probe into various wells of a Reaction 2 Bottles (220 mL each) AxSYM Probe Vessel (RV). Cleaning Solution containing 2% Tetraethylammoniumhydroxide (TEAH). • Sample and Solution 4 (Line Diluent) are pipetted into one well of Solution 4 (Line Diluent) (8A46) the RV. 1 Bottle (10 L) Solution 4 (Line Diluent) • An aliquot of the predilution mixture, pretreatment solution and Solution containing 0.1 M Phosphate Buffer. Preservative: Sodium Azide and 4 (Line Diluent) is transferred to the cuvette of the RV. Antimicrobial Agent. The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center with the processing probe. WARNINGS AND PRECAUTIONS • PROCESSING CENTER • For In Vitro Diagnostic Use • A second aliquot of the predilution mixture is transferred to the cuvette along with the AxSYM Barbiturates II U Antiserum (antibody) and AxSYM • Package insert instructions must be carefully followed. Reliability of Barbiturates II U Fluorescein Tracer. assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. • Barbiturates from the sample and the AxSYM Barbiturates II U Fluorescein Tracer compete for binding sites on the antibody molecule. SAFETY PRECAUTIONS • The intensity of polarized fluorescent light is measured by the FPIA • CAUTION: This product contains material derived from human urine. optical assembly. Human urine sourced from healthy adults has not been shown to be a source of infectious agents; however, it is recommended that all human For further information, refer to the AxSYM System Operations Manual, samples and reagents should be handled as potentially infectious Section 3. material. Use precautions as specified in the OSHA Standard on 6,7,8,9 REAGENTS Bloodborne Pathogens or other equivalent biosafety guidelines. REAGENT PACK, 100 TESTS • This product contains sodium azide; for a specific listing, refer to the REAGENTS section. Contact with acids liberates very toxic gas. This AxSYM Barbiturates II U Reagent Pack (3B29-20)* material and its container must be disposed of in a safe way. • 1 Bottle (5 mL) < 25% Barbiturates II U Antiserum (Sheep) in buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 1) • 1 Bottle (3.5 mL) Pretreatment Solution, buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 2) • 1 Bottle (11 mL) < 0.01% Barbiturates II U Fluorescein Tracer in buffer with surfactant and protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 3)

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3B29-1D-20_Eng_ReIn.indd 2 6/28/2010 12:27:52 PM HANDLING PRECAUTIONS ASSAY PARAMETERS • Do not use Reagent Packs beyond the expiration date or the maximum 1 on-board stability. A maximum of 336 cumulative hours on-board Long Assay Name (English): Barbiturates_U the AxSYM System are available when using assay file version 6 Abbrev Assay Name (English): Barbs_U 1 00 400 or higher (located on the Abused Drugs/Toxicology Assay 11 Assay Number: 527 Disk 3D54-02 or higher). A maximum of 112 cumulative hours 12 Assay Version: * on-board the AxSYM System are available when using assay file 13 Calibration Version: * version 1 00 300 (located on the Abused Drugs/Toxicology Assay Disk 14 Assay File Revision: * 3D54-01; or assay file version 1 00 200 located on the Barbiturates II 15 Assay Enabled > ON U assay disk 9B70-02). 17 Assay Type: FPIA • Do not mix reagents from different reagent packs regardless of 18 Standard Cal Reps > 2 lot number. 21 Cal A Concentration: 0.00 Refer to the AxSYM System Operations Manual, Sections 7 and 8, for 22 Cal B Concentration: 200.00 a more detailed discussion of safety and handling precautions during 23 Cal C Concentration: 400.00 system operation. 24 Cal D Concentration: 700.00 STORAGE INSTRUCTIONS 25 Cal E Concentration: 1200.00 26 Cal F Concentration: 2000.00 43 Default Dilution Protocol > UNDILUTED The AxSYM Barbiturates II U Reagent Pack, XSYSTEMS 44 Default Calibration Method > Standard Cal Barbiturates II U Calibrators and XSYSTEMS Multiconstituent Controls must 45 be stored at 2-8°C. They may be used immediately after removing them Selected Result Concentration Unit > ng/mL from the refrigerator. Calibrators and Controls should be returned to 2-8°C 46 Selected Result Decimal Places > 2 storage immediately after use. 62 Blank I-Max background intensity: * Reagents are stable until the expiration date when stored and handled 63 Min Tracer-Min net intensity: * as directed. 73 Low Limit - Normal/Therapeutic Range lower limit > 0.00 74 High Limit - Normal/Therapeutic Range upper limit > 0.00 The AxSYM Barbiturates II U Reagent Pack may be on-board the AxSYM System for a maximum of 336 cumulative hours when using the assay file 75 Low Extreme Value > 0.00 version 1 00 400 or higher located on the Abused Drugs/Toxicology Assay 76 High Extreme Value > 0.00 Disk 3D54-02 or higher; for example 42, eight-hour shifts. The AxSYM 80 Interpretation Option to use > 1 Barbiturates II U Reagent Pack may be on-board the AxSYM System for 84 Hold results with POS interpretation > OFF a maximum of 112 cumulative hours when using the assay file version 85 Hold results with NEG interpretation > OFF 1 00 300 located on the Abused Drugs/Toxicology Assay Disk 3D54-01 or 91 Low Range Undiluted: * the assay file version 1 00 200 located on the Barbiturates II U assay disk 92 High Range Undiluted: * 9B70-02; for example 14, eight-hour shifts. Recalibration may be required 116 Positive Interpretation Cutoff > 200.00 to obtain maximum on-board reagent stability. More frequent use of controls 117 Negative Interpretation Cutoff > 200.00 may be required to monitor reagent performance within the same lot. Refer to the AxSYM System Operation Manual, Sections 2, 5 and Appendices, NOTE: Parameter 45 can be edited to the alternate result unit µg/mL for further information on tracking on-board time. or µmol/L. The AxSYM Barbiturates II U values available for parameter #80 (Interpretation Option to use) are: The AxSYM Probe Cleaning Solution and Solution 4 (Line Diluent) must be stored at 15-30°C. POS Interp NEG Interp GRY Interp 1. POSITIVE NEGATIVE NONE INSTRUMENT PROCEDURE 2. NONE NONE NONE Assay File Installation Refer to the AxSYM System Operations Manual for a detailed description The AxSYM Barbiturates II U Assay File must be installed on the AxSYM of Instrument Procedures. System from one of the following software disks, prior to performing Barbiturates II U assays: Editable Interpretation Cut-off • 9B70-02 or 3D54-01 (112 hours on-board Stability) AxSYM Drugs of Abuse/Toxicology assay disk 3D54-01, or higher, installed on AxSYM System Software Version 3.0, or higher, provides the ability to • 3D54-02, or higher (336 hours on-board Stability) edit the Interpretation range. Assay Parameters “116 Positive Interpretation Refer to the AxSYM System Operations Manual, Section 2, for proper Cutoff” and “117 Negative Interpretation Cutoff” have a default setting of installation procedures. 200.00 ng/mL. Any result at or above the cutoff will provide a POSITIVE AxSYM Barbiturates II U Assay Parameters interpretation along with the numerical value. Any result below the cutoff will provide a NEGATIVE interpretation along with the numerical value. The default values for the assay parameters used for the AxSYM This assay parameter may be edited to a cutoff appropriate for your client Barbiturates II U assay are listed below. Assay parameters that can be population. When using interpretations, Assay Parameters 116 and 117 edited contain a (>) symbol. These parameters can be displayed and edited MUST be edited to the same value to avoid an incorrect interpretation according to the procedure in the AxSYM System Operations Manual, being provided for a result. Section 2: Installation Procedures and Special Requirements. In order to obtain values for the parameters with an asterisk (*), review the specific Refer to the AxSYM System Operations Manual, Section 2, for further Assay Parameter screen. Press PRINT to print the assay parameters. information on editing assay parameters. SAMPLE COLLECTION AND PREPARATION FOR ANALYSIS • The urine sample must be collected in a clean, previously unused container. Samples should be refrigerated (2-8°C) upon collection and stored frozen (-10°C or colder) if not analyzed within 48 hours.10,11 Frozen samples must be thawed and mixed thoroughly prior to analysis. Sodium azide (0.1%), boric acid (0.1%) and sodium fluoride (0.013%) may be used as urine preservatives. • The AxSYM does not provide the capability to verify sample type. It is the responsibility of the operator to verify the correct sample type(s) is (are) used in the AxSYM Barbiturates II U assay. • Inspect all samples for bubbles. Remove bubbles prior to analysis. • When shipped, samples must be packaged and labeled in compliance with applicable federal and international regulations covering the transport of clinical samples and etiologic agents.

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3B29-1D-20_Eng_ReIn.indd 3 6/28/2010 12:27:52 PM SAMPLE VOLUME SAMPLE DILUTION PROCEDURES The sample volume required to perform a single Barbiturates II U test on CAUTION: the AxSYM System varies depending on the type of sample container used. The automated dilution protocol, as described in the AxSYM System For sample cups, a ROUTINE test requires 150µL and a STAT test requires Operations Manual, Section 5, CANNOT BE USED with the AxSYM 100µL. For every additional Barbiturates II U test (ROUTINE or STAT) from Barbiturates II U assay. the same container, an additional 50µL of sample is required. Manual Dilution Protocol The sample cup minimum volumes for both STAT and ROUTINE tests are calculated by the AxSYM System. They are displayed on the Order screen If a numerical value is desired for patient samples reported as at the time the test(s) is (are) ordered, and printed in the Orderlist Report. > 2000 ng/mL, the urine sample may be manually diluted with XSYSTEMS When using Host Order Query, the Order screen information and Orderlist Barbiturates II U Calibrator A and repeated on the AxSYM System. The Report are not available. Refer to the AxSYM System Operations Manual, concentration reported by the AxSYM System must be multiplied by the Section 5, for a description of the Host Order Query option. manual dilution factor to obtain the final sample concentration. If the assay is configured for auto retest, the additional sample volume Final Sample Concentration = Reported Concentration x Manual Dilution Factor Manual needed for the retest will not be displayed on the Order screen at the (Volume of Sample + Volume of Dilution Reagent) Dilution Factor = time the test(s) is(are) ordered. Therefore, the total sample volume should Volume of Sample include an additional 50µL of sample. Refer to the AxSYM System Operations Manual, Section 5, for sample QUALITY CONTROL PROCEDURES volume requirements in primary or aliquot tubes and calibrators/control CALIBRATION requirements for multiple reagent lots. The AxSYM Barbiturates II U assay must be calibrated using the Standard AxSYM BARBITURATES II U PROCEDURE Calibration (6 - point) procedure. Standard Calibration Materials Provided To perform an AxSYM Barbiturates II U Standard Calibration, test XSYSTEMS • 3B29-99 AxSYM Barbiturates II U Reagent Kit, Barbiturates II U Calibrators A, B, C, D, E, and F in duplicate. A single sample containing: of all levels of controls must be tested to evaluate the assay calibration. AxSYM Barbiturates II U Once the AxSYM Barbiturates II U calibration is accepted and stored, all 100 subsequent samples may be tested without further calibration unless: Materials Required But Not Provided • A reagent pack with a new lot number is used. • 9669-07 XSYSTEMS Barbiturates II U Calibrators • Control values are out of their specific range. • 9687-12 XSYSTEMS Multiconstituent Controls Refer to the AxSYM System Operations Manual, Section 6, for: • 8A46 • Setting up an assay calibration • 9A35-05 AxSYM • When recalibration may be necessary • 8A76-01 • Calibration Verification • Pipettes/Pipette tips (optional) to deliver the volume specified on the The AxSYM System verifies that the results of an assay calibration meet the order screen specifications assigned to selected validity parameters. An error message occurs when the calibration fails to meet a specification. Refer to the CAUTION: AxSYM Operations Manual, Section 10, for an explanation of the corrective • When manually dispensing sample into sample cups, verify that actions for the error code. Refer to the AxSYM System Operations Manual, dispensing equipment does not introduce cross contamination and Appendices, for an explanation of the calibration validity parameters that delivers the specified sample volume. Use a separate pipette tip for may be used by the AxSYM System. each sample. Operator Verification • For optimal performance it is important to follow the routine maintenance An acceptable Barbiturates II U calibration curve should have all control procedures defined in the AxSYM System Operations Manual, Section values within the acceptable ranges. 9. If your laboratory requires more frequent maintenance, follow those procedures. QUALITY CONTROL Assay Procedure The recommended control requirement for an AxSYM Barbiturates II U assay is a single sample of at least two control levels tested once every Refer to Sections 5 and 6 of the AxSYM System Operations Manual 24 hours, each day of use. Controls may be placed in any position in the for detailed steps for performing assay calibrations and sample Sample Carousel. testing procedures. If the quality control procedures in your laboratory require more frequent Prior to ordering tests, confirm that the System inventory of Reaction Vessels use of controls to verify test results, follow those procedures. and Solution 4 (Line Diluent) is sufficient. To achieve maximum on-board reagent stability, more frequent use of The Orderlist Report contains sample placement information and STAT controls may be required to monitor reagent performance within the sample volume requirements for all ordered tests. It is recommended that same lot. this report be referenced when loading samples into sample segments. When using Host Order Query, the Orderlist Report is not available. Refer Ensure that assay control values are within the concentration ranges to the AxSYM System Operations Manual, Section 5, for a description of specified in the package insert. Refer to the REAGENTS, CONTROLS the Host Order Query option. section of this package insert for XSYSTEMS Multiconstituent Control ranges for AxSYM assays. CAUTION: When operating the AxSYM System, always observe the following: INDICATIONS OF INSTABILITY OR DETERIORATION OF REAGENTS • The System status must be WARMING, PAUSED, READY, or STOPPED When a barbiturates control value is out of the specified range, it may before adding or removing sample segments, reagent packs or Reaction indicate deterioration of the reagents or errors in technique. Associated Vessels (RVs). test results may be invalid and require retesting. Assay recalibration may • An “Error Code 5066 Matrix cell not detected, trap door, processing be indicated. Refer to the AxSYM System Operations Manual, Section 10, center” may be displayed when the instrument homes the motors. for further troubleshooting information. If performing only FPIA (and/or REA) assays, select OK to proceed The AxSYM System has a capability to generate a Levey-Jennings plot with testing. of each assay’s quality control performance. Refer to the AxSYM System • Do not open the Interior Waste Door or the AxSYM Processing Center Operations Manual, Section 5, for further information. At the discretion of Cover while any test is in process. If opened, all processing will stop. the laboratory, selected quality control rules may be applied to the quality Tests in process will be terminated and must be repeated. control data. • When testing is completed, it is recommended that samples and the AxSYM Barbiturates II U Reagent Pack are removed from the Sampling Center to maximize the on-board reagent pack use. Store Reagent Pack at 2-8°C.

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3B29-1D-20_Eng_ReIn.indd 4 6/28/2010 12:27:52 PM RESULTS Added Concentration Concentration The AxSYM Barbiturates II U assay is a semi-quantitative reagent system. Concentration in urine in Solution 4 Percent (%) The AxSYM Barbiturates II U assay provides only a preliminary analytical (ng/mL) (ng/mL) (ng/mL) Recovery result. A more specific alternate chemical method must be used in 200.00 201.52 200.29 99.39 order to obtain a confirmed analytical result. Gas chromatography/mass 300.00 290.70 276.90 95.26 spectrometry (GC/MS) is the preferred confirmatory method. 400.00 393.19 406.15 103.30 A Four Parameter Logistics Fit Method (4PLC, Y weighted) is used to 700.00 712.32 689.10 96.70 generate the AxSYM Barbiturates II U Standard calibration curve. 800.00 743.72 783.44 105.34 The calibration curve is stored in memory and concentrations of drug 1200.00 1190.84 1224.95 102.86 1500.00 1470.64 1395.56 94.90 in controls and unknown samples are calculated from this curve using polarization values generated. Average Recovery: 99.7 ± 3.9% Alternate Result Unit Sensitivity The default result unit for AxSYM Barbiturates II U is ng/mL. When selecting The sensitivity of the AxSYM Barbiturates II U assay was calculated to the alternate result unit, µmol/L, the conversion factor used by the AxSYM be 60.00 ng/mL. This sensitivity is defined as the lowest measurable System is 0.0042. When selecting the alternate result unit, µg/mL, the concentration which can be distinguished from zero with at least conversion factor used by the AxSYM System is 0.001. 95% confidence. Flags Specificity Some results may contain information in the Flags field. For a description Cross-reactivity was tested for the commonly used barbiturates and of the flags that may appear in this field, refer to the AxSYM System metabolites. The following compounds cross-react above the sensitivity Operations Manual, Sections 1 and 2. (60.00 ng/mL) of the AxSYM Barbiturates II U assay: LIMITATIONS OF THE PROCEDURE CONCENTRATION As with all analyte determinations, the Barbiturates II U value should be COMPOUND TESTED (ng/mL) used in conjunction with information available from clinical evaluation and 400 other diagnostic procedures. Urine samples with a background intensity 200 greater than the allowable value are flagged with error code “1065 Invalid test results, background intensity too high, (#).” These samples must NOT Amobarbital 700 BE DILUTED AND RERUN. An alternative analysis method must be used 200 on these samples. 2,000 5-ethyl-5-(4-hydroxyphenyl)-barbituric acid 2,000 EXPECTED VALUES 200 Concentrations of drugs and/or metabolite(s) detected in urine have not 200 been correlated to drug levels in the bloodstream nor with degree of 200 impairment. The presence of a drug and/or metabolite(s) in urine is only 400 an indication of previous drug exposure.12 200 SPECIFIC PERFORMANCE CHARACTERISTICS 100,000 Precision 1,000,000 Precision was determined as described in National Committee for Clinical 1,000,000 Laboratory Standards (NCCLS) Protocol EP5-T2.13 A three member urine Pentobarbital 200 panel was assayed, using a single lot of reagents and a single calibration, 200 in replicates of 2 at two separate times per day for 20 days. Data shown 200 from this study yielded %CV of less than 10%. Representative data are Thiopental 2,000 shown in the following table. Cross-reactivity was also tested with compounds that have similar Target Mean chemical structure or are used concurrently. The following compounds Control Concentration Concentration Within Run Total Run cross-react above the sensitivity (60.00 ng/mL) of the AxSYM Value (ng/mL) Value (ng/mL) SD %CV SD %CV Barbiturates II U assay: Low 300 276.98 15.95 5.76 23.05 8.32 CONCENTRATION Medium 800 703.42 37.09 5.27 43.41 6.17 High 1500 1362.94 55.17 4.05 83.21 6.10 COMPOUND TESTED (ng/mL) Accuracy By Recovery Aminoglutethimide 100,000 Two sets of calibrators and controls were prepared by adding known Dezocine 1,000,000 quantities of secobarbital to human urine and AxSYM Solution 4 (Line 10,000 Diluent) to levels of 200, 300, 400, 700, 800, 1200 and 1500 ng/mL. The 5-(p-Hydroxyphenyl)-5- 500,000 analyzer was calibrated with urine calibrators and both sets of calibrators phenylhydantoin (HPPH) and controls were assayed relative to this calibration. Percent recovery = 100,000 100 x (“concentration in Solution 4 (line diluent)” divided by “concentration Retinoic Acid 1,000,000 in urine”). Representative data follow:

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3B29-1D-20_Eng_ReIn.indd 5 6/28/2010 12:27:53 PM The following compounds do not cross-react above the sensitivity INTERFERENCES (60.00 ng/mL) of the AxSYM Barbiturates II U assay. (Compounds tested The compounds listed below, added to human urine, resulted in less at 100,000 ng/mL, unless otherwise indicated): than 10% error in detecting added drug when assayed with the AxSYM Barbiturates II U assay. * Acetaminophen Melanin Acetylsalicylic Acid Meperidine COMPOUND CONCENTRATION TESTED Methadone 1 g/dL Methadone Primary Ascorbic Acid 1. 5 g/dL Amoxicillin Metabolite (EDDP) Bilirubin 0.25 mg/dL Ampicillin d-Methamphetamine Creatinine 500 mg/dL Aspartame d,l-Methamphetamine Ethanol 1 g/dL Barbituric Acid 3,4-Methylenedioxy- Glucose 2 g/dL Benzocaine amphetamine (MDA) Hemoglobin (lysed red blood cells) 115 mg/dL Benzoic Acid 3,4-Methylenedioxy-N- Oxalic Acid 100 mg/dL Benzoylecgonine ethylamphetamine (MDE) Riboflavin 7.5 mg/dL * Buprenorphine 3,4-Methylenedioxy- Sodium Chloride 6 g/dL Caffeine methamphetamine (MDMA) Total Protein 0.05 g/dL Calcium Hypochlorite Methylphenidate Urea 6 g/dL Chloramphenicol The presence of detergents in samples potentially interferes with Chloroquine Naloxone immunoassay results. Chlorpheniramine Naltrexone Bleach (hypochlorite) is a strong oxidizing agent. As a consequence, * Naproxen bleach may cause oxidation of some analytes, thus reducing the amount Clindamycin Niacinamide available for analysis. This may result in lower analytic results, regardless of the methodology.14 Cocaine Nicotine There is the possibility that other substances and/or factors not listed above Dextromethorphan Oxymorphone may interfere with the test and cause false results. * Penicillin G ACCURACY BY CORRELATION WITH REFERENCE ASSAYS Digoxin Phenothiazine The AxSYM Barbiturates II U assay was evaluated for concordance to TDx Dihydrocodeine Phenylbutazone and GC/MS by assaying drug-free and drug-containing urine samples for Dihydromorphine * Phenylpropanolamine barbiturates and metabolites. Samples were analyzed on-site at Abbott 1,3-Dimethylbarbituric Acid Laboratories on AxSYM and TDx. GC/MS analysis of these samples was * Procainamide performed at a reference laboratory in Tennessee and on-site at Abbott Ecgonine # Laboratories. Concordance is related to selected cut-off. The performance of AxSYM Barbiturates II U assay was evaluated at several cut-off levels ** Ephedrine Prolintane (cut-off is the level above which the AxSYM flags a sample as positive for * Epinephrine * the desired analyte). The cut-off for GC/MS methodology is chosen by * Erythromycin ** Pseudoephedrine the reference laboratory. Estriol Quinine * Fenoprofen Salicylic Acid (TP+TN) Concordance = x 100 * Furosemide Serotonin (TP+FP+TN+FN) Gentisic Acid Sulindac TP = True positives * Guaiacol Glyceryl Ether Tetracycline Haloperidol 11-Nor-delta-9-tetrahydro- TN = True negatives Histamine cannabinol-9-carboxylic FP = False positives Hydralazine Acid FN = False negatives Hydrocodone Theophylline 200 ng/mL n=100 *TDx Pos TDx Neg GC/MS Pos GC/MS Neg Hydromorphone Tolbutamide * Ibuprofen Trifluoperazine AxSYM Pos 88 0 90 0 Isoproterenol Trimethoprim AxSYM Neg 0 10 4** 6 * Tyramine CONCORDANCE Ketoprofen AxSYM vs. TDx = 100% Lovastatin AxSYM vs. GC/MS = 96% 400 ng/mL n=100 *TDx Pos TDx Neg GC/MS Pos GC/MS Neg # Tested at 10,000 ng/mL AxSYM Pos 78 2 82 0 * Tested at 1,000,000 ng/mL AxSYM Neg 0 18 12 6 ** Tested at 3,000,000 ng/mL CONCORDANCE AxSYM vs. TDx = 98% AxSYM vs. GC/MS = 88% 700 ng/mL n=100 *TDx Pos TDx Neg GC/MS Pos GC/MS Neg AxSYM Pos 75 1 78 0 AxSYM Neg 0 22 16 6

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3B29-1D-20_Eng_ReIn.indd 6 6/28/2010 12:27:53 PM CONCORDANCE AxSYM, TDx and XSYSTEMS are trademarks of Abbott Laboratories in AxSYM vs. TDx = 99% various jurisdictions. AxSYM vs. GC/MS = 84% * Results on 2 TDx samples were not reportable because Blank I-max background exceeded. ** AxSYM TDx GC/MS (ng/mL) (ng/mL) (ng/mL) CMPD ID ABBOTT 144.95 123.34 231 Phenobarbital Max-Planck-Ring 2 65205 Wiesbaden 161.90 128.09 284 Phenobarbital Germany 156.57 128.59 272 Phenobarbital +49-6122-580 172.56 139.38 311 Phenobarbital

June 2010 AxSYM “Positive” = Concentration greater than or equal to the cut-off, 200, 400 or 700 ng/mL of Secobarbital. ©1995, 2010 Abbott Laboratories TDx “Positive” = Concentration greater than or equal to the cut-off, 200, 400 or 700 ng/mL of Secobarbital. GC/MS “Positive” = Concentration greater than or equal to 100 ng/mL of amobarbital, butabarbital, butalbital, pentobarbital, phenobarbital and/or secobarbital. BIBLIOGRAPHY 1. Hawks RL. Analytical Methodology. In: Chiang CN, Hawks RL, eds. Urine testing for drugs of abuse. National Institute on Drug Abuse (NIDA). Research Monograph 73. Rockville, MD: Department of Health and Human Services, 1986; 35-8. 2. Huff BB, ed. Physicians’ Desk Reference. Oradell, NJ: Medical Economics Co., Inc., 1985;39: 1172-4. 3. Hofman FG. A handbook on drug and abuse: The biomedical aspects. New York: Oxford University Press, 1983;116-27. 4. Gorodetzky CW. Detection of drugs of abuse in biological fluids. In: Martin WR, ed. Drug addiction I. New York: Springer-Verlag, 1977;319-409. 5. Stead AH, et al. Drug misuse - The barbiturate problem. J Forensic Sci Soc, 1981;21:41-53. 6. US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 1910.1030, Bloodborne pathogens. 7. US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office; January 2007. 8. World Health Organization. Laboratory Biosafety Manual. 3rd ed. Geneva: World Health Organization; 2004. 9. Clinical and Laboratory Standards Institute. Protection of Laboratory Workers from Occupationally Acquired Infections: Approved Guideline -Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2005. 10. National Institute on Drug Abuse and Department of Health and Human Services. The NIDA Guidelines. Subpart B, Section 2.4 (c, h). Federal Register, Vol. 59, No. 110, 9 June 1994. 11. National Committee for Clinical Laboratory Standards. Urine Drug Testing in the Clinical Laboratory; Proposed Guideline. NCCLS Document T/DM8-P. Villanova, PA: NCCLS, 1993. 12. Baselt RC. Urine drug screening by immunoassay: Interpretation of results. In: Baselt RC, ed. Advances in analytical toxicology. Foster City, CA: Biomedical Publications, 1984; Vol. 1: 81-123. 13. National Committee for Clinical Laboratory Standards. Evaluation of precision performance of clinical chemistry devices-Second Edition; Tentative Guideline. NCCLS Document EP5-T2. Villanova, PA: NCCLS, 1992. 14. Fieser LF, Fieser M. Reagents for Organic Synthesis. New York: John Wiley & Sons, Inc., 1967-84: Vols. 1 - 11.

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