E Metabolite 3B24-20 34-5076/R9 Cocaine Metabolite

Customer Service United States: 1-877-4ABBOTT International: Call your Abbott Representative

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.

Read Highlighted Changes Revised September, 2008

Key to symbols used

List Number Expiration Date

In Vitro Diagnostic Medical Device Lot Number

Store at 2-8°C Calibrator (A-F)

Store at 15-30°C Control Low, Medium, High (L, M, H)

Consult instructions for use Sample Cups

Reagent Pack Manufacturer

Authorized Representative Reaction Vessels

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

Abbott Laboratories Diagnostics Division Abbott Park, IL 60064 USA Printed in USA 1

33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 1 99/17/2008/17/2008 11:38:4811:38:48 AAMM Colors: PMS 3165 PMS 222 BLACK LE: Pam DTP: Scott NAME • Cocaine Metabolite from the sample and the AxSYM Cocaine Cocaine Metabolite Metabolite Fluorescein Tracer compete for binding sites on the antibody molecule. INTENDED USE • The intensity of polarized fluorescent light is measured by the FPIA The AxSYM Cocaine Metabolite assay is a semi-quantitative reagent optical assembly. system for the detection of the primary urinary metabolite of Cocaine, benzoylecgonine in human urine. Measurements obtained are used as an For further information, refer to the AxSYM System Operations Manual, aid in the diagnosis and treatment of cocaine use or abuse. Section 3. The AxSYM Cocaine Metabolite assay provides only a preliminary REAGENTS analytical test result. A more specific alternate chemical method REAGENT PACK, 100 TESTS must be used in order to obtain a confirmed analytical result. Gas AxSYM Cocaine Metabolite Reagent Pack (3B24-20) * chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method.1 Clinical considerations and professional • 1 Bottle (5.4 mL) < 5% Cocaine Metabolite Antiserum (Sheep) judgment should be applied to any drug of abuse test result, particularly in buffer with protein stabilizer. Preservative: Sodium Azide. when preliminary positive results are used. (Reagent Bottle 1). • 1 Bottle (4.0 mL) Pretreatment Solution, buffer with protein stabilizer. SUMMARY AND EXPLANATION OF TEST Preservative: Sodium Azide. (Reagent Bottle 2). The AxSYM Cocaine Metabolite assay utilizes Fluorescence Polarization • 1 Bottle (5.3 mL) < 0.01% Cocaine Metabolite Fluorescein Tracer Immunoassay (FPIA) technology. Refer to the AxSYM System Operations in buffer with surfactant and protein stabilizer. Preservative: Sodium Manual, Section 3, under Principles of Operation for a discussion of this Azide. (Reagent Bottle 3). technology. * 3B24-99 includes an AxSYM Cocaine Metabolite Reagent Pack Cocaine is a frequently abused drug. The drug is administered by nasal (100 Tests) and reaction vessels (100 each). 3B24-20 includes these insufflation, intravenous injection or in the free base form as smoke items for international shipments. inhalation. The urinary elimination of cocaine and its metabolite begins within 20 minutes of its intranasal administration.2-6 A single dose is excreted CALIBRATORS in a 24-hour urine as cocaine (1 - 9 %), benzoylecgonine (35 - 54 %), XSYSTEMS Cocaine Metabolite Calibrators (9670-06) ecgonine methyl ester (32 - 49 %) and ecgonine (not quantitated).2 6 Bottles (4 mL A, 2.5 mL each B-F) of XSYSTEMS Cocaine Metabolite The Cocaine Metabolite assay is designed to perform at a variety of Calibrators. Calibrator A contains human urine and Calibrators B through commonly used cut-off levels. The analyzer has been factory set at F contain benzoylecgonine prepared in human urine to yield the following 300.00 ng/mL. NIDA recommends a 300 ng/mL cut-off for screening assays concentrations: detecting Cocaine Metabolite (Federal Register June 9, 1994). Abbott Laboratories recommends the use of this cut-off, if appropriate for your Benzoylecgonine Concentration client population. To configure the cut-off in your laboratory refer to the INSTRUMENT PROCEDURE section in this insert. Bottle (ng/mL) (μmol/L) Selection of the cut-off value should be based on review of the laboratory’s 0 0.00 and it’s clients’ needs, sensitivity of available confirmation methods and 300 1.04 the sensitivity and cross-reactivity data of the assay itself. 1000 3.46 2000 6.91 BIOLOGICAL PRINCIPLES OF THE PROCEDURE 3000 10.37 The AxSYM Cocaine Metabolite assay is based on Fluorescence 5000 17.28 Polarization Immunoassay (FPIA) technology. The AxSYM Cocaine Preservative: Sodium Azide. Metabolite Reagents and sample are pipetted in the following sequence: CONTROLS SAMPLING CENTER XSYSTEMS Multiconstituent Controls (9687-12) • Sample and all AxSYM Cocaine Metabolite Reagents required for one test are pipetted by the sampling probe into various wells of a 2 Bottles each of Low, Medium and High (4.5 mL each) prepared in human Reaction Vessel (RV). urine diluent to read within the following ranges: • Sample and Solution 4 (Line Diluent) are pipetted into one well of Benzoylecgonine the RV. Concentration Range The RV is immediately transferred into the Processing Center. Further Bottle (ng/mL) (μmol/L) (ng/mL) (μmol/L) pipetting is done in the Processing Center with the processing probe. 500 1.73 342.66 - 657.34 1.184 - 2.272 PROCESSING CENTER 1500 5.18 1098.20 - 1901.80 3.795 - 6.573 3000 10.37 2185.92 - 3814.08 7.554 - 13.182 • An aliquot of the predilution mixture, pretreatment/antibody mixture and Solution 4 (Line Diluent) are transferred to the cuvette of the RV. Preservative: Sodium Azide. • After an incubation period, a second aliquot of the antibody/pretreatment The calibrators and controls are matched to an Abbott internal reference mixture, Cocaine Metabolite Fluorescein Tracer and a second aliquot standard. This internal reference standard is manufactured by gravimetric of the predilution mixture are transferred to the cuvette. methods using benzoylecgonine anhydrous (not less than purity 99%) at each concentration level. OTHER REAGENTS AxSYM Probe Cleaning Solution (9A35-05) 2 Bottles (220 mL each) AxSYM Probe Cleaning Solution containing 2% Tetraethylammoniumhydroxide (TEAH).

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 2 99/17/2008/17/2008 11:38:5311:38:53 AAMM Solution 4 (Line Diluent) (8A46) 1 Bottle (10 L) Solution 4 (Line Diluent) The AxSYM Probe Cleaning Solution and Solution 4 containing 0.1 M Phosphate Buffer. Preservatives: Sodium Azide and (Line Diluent) must be stored at 15 - 30°C. Antimicrobial Agent. INSTRUMENT PROCEDURE WARNINGS AND PRECAUTIONS Assay File Installation For In Vitro Diagnostic Use. The AxSYM Cocaine Metabolite Assay File must be installed on the AxSYM SAFETY PRECAUTIONS System from one of the following software disks, prior to performing • CAUTION: This product contains material derived from human urine. Cocaine Metabolite assays: Human urine sourced from healthy adults has not been shown to • 9B65-02 or 3D54-01 (112 hours on-board Stability) be a source of infectious agents, however, it is recommended that • 3D54-02, or higher (336 hours on-board Stability) all human samples and reagents should be handled as potentially infectious material. Use precautions as specified in the OSHA Refer to the AxSYM System Operations Manual, Section 2, for proper Standard on Bloodborne Pathogens or other equivalent biosafety installation procedures. guidelines.7,8,9,10 AxSYM Cocaine Metabolite Assay Parameters • This product contains sodium azide; for a specific listing, refer to the The default values for the assay parameters used for the AxSYM Cocaine REAGENTS section. Contact with acids liberates very toxic gas. This Metabolite assay are listed below. Assay parameters that can be edited material and its container must be disposed of in a safe way. contain a (>) symbol. These parameters can be displayed and edited • For product not classified as dangerous per European Directive according to the procedure in the AxSYM System Operations Manual, 1999/45/EC as amended - Safety data sheet available for professional Section 2: Installation Procedures and Special Requirements. In order user on request. to obtain values for the parameters with an asterisk (*), review the specific Assay Parameter screen. Press PRINT to print the assay parameters. HANDLING PRECAUTIONS Assay Parameters • Do not use Reagent Packs beyond the expiration date or the maximum on-board stability. A maximum of 336 cumulative hours on-board 1 Long Assay Name (English): Cocaine_Met the AxSYM System are available when using assay file version 6 Abbrev Assay Name (English): Cocaine 11 Assay Number: 500 1 00 400 or higher (located on the Abused Drugs/Toxicology Assay 12 Assay Version: * Disk 3D54-02 or higher). A maximum of 112 cumulative hours on-board 13 Calibration Version: * the AxSYM System are available when using assay file version 14 Assay File Revision: * 1 00 300 (located on the Abused Drugs/Toxicology Assay Disk 15 Assay Enabled > ON 3D54-01; or assay version 1 00 200 located on the Cocaine Metabolite 17 Assay Type: FPIA Assay Disk 9B65-02). 18 Standard Cal Reps > 2 • Do not mix reagents from different reagent packs regardless of 21 Cal A Concentration: 0.00 22 Cal B Concentration: 300.00 lot number. 23 Cal C Concentration: 1000.00 Refer to the AxSYM System Operations Manual, Sections 7 and 8, for 24 Cal D Concentration: 2000.00 a more detailed discussion of safety and handling precautions during 25 Cal E Concentration: 3000.00 system operation. 26 Cal F Concentration: 5000.00 43 Default Dilution Protocol > UNDILUTED STORAGE INSTRUCTIONS 44 Default Calibration Method > Standard Cal 45 Selected Result Concentration Units > ng/mL The AxSYM Cocaine Metabolite Reagent Pack, 46 Selected Result Decimal Places > 2 XSYSTEMS Cocaine Metabolite Calibrators and XSYSTEMS Multiconstituent 62 Blank I-Max background intensity: * Controls must be stored at 2 - 8°C. They may be used immediately after 63 Min Tracer-Min net intensity: * 73 Low Limit - Normal/Therapeutic Range lower limit > 0.00 removing them from the refrigerator. Calibrators and Controls should be 74 High Limit - Normal/Therapeutic Range upper limit > 0.00 returned to 2 - 8°C storage immediately after use. 75 Low Extreme Value > 0.00 Reagents are stable until the expiration date when stored and handled 76 High Extreme Value > 0.00 as directed. 80 Interpretation Option to use > 1 84 Hold results with POS interpretation > OFF The AxSYM Cocaine Metabolite Reagent Pack may be on-board the AxSYM 85 Hold results with NEG interpretation > OFF System for a maximum of 336 cumulative hours when using the assay file 91 Low Range Undiluted: * version 1 00 400 or higher located on the Abused Drugs/Toxicology Assay 92 High Range Undiluted: * Disk 3D54-02 or higher; for example 42, eight-hour shifts. The AxSYM 116 Positive Interpretation Cutoff > 300.00 Cocaine Metabolite Reagent Pack may be on-board the AxSYM System 117 Negative Interpretation Cutoff > 300.00 for a maximum of 112 cumulative hours when using the assay file version NOTE: Parameter 45 can be edited to the alternate result unit μg/mL 1 00 300 located on the Abused Drugs/Toxicology Assay Disk 3D54-01 or μmol/L. or the assay version 1 00 200 located on the Cocaine Metabolite Assay Disk 9B65-02, for example 14, eight-hour shifts. Recalibration may be required to obtain maximum on-board reagent stability. More frequent use of controls may be required to monitor reagent performance within the same lot. Refer to the AxSYM System Operations Manual, Sections 2 and 5, for further information on tracking on-board time.

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 3 99/17/2008/17/2008 11:38:5311:38:53 AAMM The AxSYM Cocaine Metabolite values available for parameter #80 AxSYM COCAINE METABOLITE PROCEDURE (Interpretation Option to use) are: Materials Provided POS Interp NEG Interp GRY Interp • 3B24-99 AxSYM Cocaine Metabolite Reagent Kit, 1. POSITIVE NEGATIVE NONE containing: 2. NONE NONE NONE AxSYM Cocaine Metabolite Refer to the AxSYM System Operations Manual for a detailed description 100 of Instrument Procedures. Materials Required But Not Provided Selection of a cut-off • 9670-06 XSYSTEMS Cocaine Metabolite Calibrators AxSYM Drugs of Abuse/Toxicology Assay Disk 3D54-01, or higher, installed • 9687-12 XSYSTEMS Multiconstituent Controls on AxSYM System Software Version 3.0, or higher, provides the ability to • 8A46 edit the Interpretation range. Assay Parameters “116 Positive Interpretation • 9A35-05 AxSYM Cutoff” and “117 Negative Interpretation Cutoff” have a default setting of 300.00 ng/mL. Any result at or above the Cut-off will provide a POSITIVE • 8A76-01 interpretation along with the numerical value. Any result below the Cut-off • Pipettes/Pipette tips (optional) to deliver the volume specified on the will provide a NEGATIVE interpretation along with the numerical value. This order screen assay parameter may be edited to a Cut-off appropriate for your client CAUTION: population. When using interpretations, Assay Parameters 116 and 117 MUST be edited to the same value to avoid an incorrect interpretation • When manually dispensing sample into sample cups, verify that being provided for a result. dispensing equipment does not introduce cross contamination and delivers the specified sample volume. Use a separate pipette tip for Refer to the AxSYM System Operations Manual, Section 2, for further each sample. information on editing assay parameters. • For optimal performance it is important to follow the routine SAMPLE COLLECTION AND PREPARATION FOR maintenance procedures defined in the AxSYM System Operations ANALYSIS Manual, Section 9. If your laboratory requires more frequent • The urine sample must be collected in a clean, previously unused maintenance, follow those procedures. container. Samples should be refrigerated (2 - 8°C) upon collection Assay Procedure and stored frozen (-10°C or colder) if not analyzed within 48 hours.11,12 Sections 5 and 6 of the AxSYM System Operations Manual can be removed Frozen samples must be thawed and mixed thoroughly prior to analysis. for use at the instrument. They contain detailed steps for performing assay Sodium azide (0.1%), boric acid (0.1%) and sodium fluoride (0.013%) calibration and sample testing procedures. may be used as urine preservatives. Prior to ordering tests, confirm that the System inventory of Reaction • The AxSYM does not provide the capability to verify sample type. It is Vessels and Solution 4 (Line Diluent) is sufficient. the responsibility of the operator to verify the correct sample type(s) is(are) used in the AxSYM Cocaine Metabolite assay. The Orderlist Report contains sample placement information and STAT sample volume requirements for all ordered tests. It is recommended that • Inspect all samples for bubbles. Remove bubbles prior to analysis. this report be referenced when loading samples into sample segments. • When shipped, samples must be packaged and labeled in compliance When using Host Order Query, the Orderlist Report is not available. Refer with applicable federal and international regulations covering the to AxSYM System Operations Manual, Section 5, for a description of the transport of clinical samples and etiologic agents. Host Order Query option. SAMPLE VOLUME CAUTION: When operating the AxSYM System, always observe The sample volume required to perform a single cocaine metabolite test the following: on the AxSYM System varies depending on the type of sample container • The System status must be WARMING, PAUSED, READY, or STOPPED used. For sample cups, a ROUTINE test requires 150 μL and a STAT test before adding or removing sample segments, reagent packs or requires 94 μL. For every additional cocaine metabolite test performed Reaction Vessels (RV’s). (ROUTINE or STAT) from the same container, an additional 44 μL of sample is required. • An “Error Code 5066 Matrix cell not detected, trap door, processing center” may be displayed when the instrument homes the motors. If The sample cup minimum volumes for both STAT and ROUTINE tests are performing only FPIA (and/or REA®) assays, select OK to proceed calculated by the AxSYM System. They are displayed on the Order screen with testing. at the time the test(s) is(are) ordered, and printed in the Orderlist Report. When using Host Order Query, the Order screen information and the • Do not open the Interior Waste Door or the AxSYM Processing Center Orderlist Report are not available. Refer to the AxSYM System Operations Cover while any test is in process. If opened, all processing will stop. Manual, Section 5, for a description of the Host Order Query option. Tests in process will be terminated and must be repeated. If the assay is configured for auto retest, the additional sample volume • When testing is completed, it is recommended that samples and the needed for the retest will not be displayed on the Order screen at the AxSYM Cocaine Metabolite Reagent Pack are removed from the time the test(s) is(are) ordered. Therefore, the total sample volume should Sampling Center to maximize the on-board reagent pack use. Store include an additional 44 μL of sample. Reagent Pack at 2 - 8°C. Refer to the AxSYM System Operations Manual, Section 5, for sample volume requirements in primary or aliquot tubes and calibrator/control requirements for multiple reagent lots.

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 4 99/17/2008/17/2008 11:38:5411:38:54 AAMM SAMPLE DILUTION PROCEDURES INDICATIONS OF INSTABILITY OR DETERIORATION OF REAGENTS CAUTION: The automated dilution protocol, as described in the AxSYM When a control value is out of the specified range, it may indicate System Operations Manual, Section 5, CANNOT BE USED with the AxSYM deterioration of the reagents or errors in technique. Associated test results Cocaine Metabolite assay. may be invalid and require retesting. Assay recalibration may be indicated. Manual Dilution Protocol Refer to the AxSYM System Operations Manual, Section 10, for further troubleshooting information. If a numerical value is desired for patient samples reported as > 5000 ng/mL, the urine sample may be manually diluted with XSYSTEMS The AxSYM System has a capability to generate a Levey-Jennings plot Cocaine Metabolite Calibrator A and repeated on the AxSYM System. The of each assay’s quality control performance. Refer to the AxSYM System concentration reported by the AxSYM System must be multiplied by the Operations Manual, Section 5, for further information. At the discretion manual dilution factor to obtain the final sample concentration. of the laboratory, selected quality control rules may be applied to the Final Sample quality control data. Concentration = Reported Concentration x Manual Dilution Factor RESULTS Manual Dilution Factor = (Volume of Sample + Volume of Dilution Reagent) The AxSYM Cocaine Metabolite assay is a semi-quantitative reagent Volume of Sample system. The AxSYM Cocaine Metabolite assay provides only a preliminary QUALITY CONTROL PROCEDURES analytical result. A more specific alternate chemical method must be used CALIBRATION in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. The AxSYM Cocaine Metabolite assay must be calibrated using a Standard Calibration (6-point) procedure. A Four Parameter Logistic Fit Method (4PLC, Y weighted) is used to generate the AxSYM Cocaine Metabolite standard curve. The calibration To review the detailed results of a calibration curve, refer to Section 6 of curve is stored in memory and concentrations of drug in controls and the AxSYM System Operations Manual. unknown samples are calculated from this curve using polarization values Standard Calibration generated. To perform an AxSYM Cocaine Metabolite Standard Calibration, test Alternate Units XSYSTEMS Cocaine Metabolite Calibrators A, B, C, D, E, and F in duplicate. The default result unit for AxSYM Cocaine Metabolite is ng/mL. When A single sample of all levels of controls must be tested to evaluate the selecting the alternate result unit, μmol/L, the conversion factor used by assay calibration. the AxSYM System is 0.003456. When selecting the alternate result unit Once the AxSYM Cocaine Metabolite calibration is accepted and stored, μg/mL, the conversion factor used by the AxSYM System is 0.001. all subsequent samples may be tested without further calibration unless: Flags • A reagent pack with a new lot number is used. Some results may contain information in the Flags field. For a description • Control values are out of their specific range. of the flags that may appear in this field, refer to the AxSYM System Refer to the AxSYM System Operations Manual, Section 6, for: Operations Manual, Sections 1 and 2. • Setting up an assay calibration LIMITATIONS OF THE PROCEDURE • When recalibration may be necessary As with all analyte determinations, the Cocaine Metabolite value should • Calibration Verification be used in conjunction with information available from clinical evaluation and other diagnostic procedures. The AxSYM System verifies that the results of an assay calibration meet the specifications assigned to selected validity parameters. An error Urine samples with a background intensity greater than the allowable value message occurs when the calibration fails to meet a specification. Refer are flagged with error code “1065 Invalid test results, background intensity to the AxSYM System Operations Manual, Section 10, for an explanation too high, (#).” These samples must NOT BE DILUTED AND RERUN. An of the corrective actions for the error code. Refer to the AxSYM System alternative analysis method must be used on these samples. Operations Manual, Appendices, for an explanation of the calibration EXPECTED VALUES validity parameters that may be used by the AxSYM System. Concentrations of drugs and/or metabolite(s) detected in urine have not Operator Verification been correlated to drug levels in the bloodstream nor with degree of An acceptable Cocaine Metabolite calibration curve should have all control impairment. The presence of a drug and/or metabolite(s) in urine is only values within the acceptable ranges. an indication of previous drug exposure.2 QUALITY CONTROL SPECIFIC PERFORMANCE CHARACTERISTICS The recommended control requirement for an AxSYM Cocaine Metabolite Precision assay is a single sample of at least two control levels tested once every Precision was determined as described in the National Committee for 24 hours, each day of use. Controls may be placed in any position in the Clinical Laboratory Standards (NCCLS) Protocol EP5-T2.13 A three member Sample Carousel. urine panel was assayed, using a single lot of reagents and a single If the quality control procedures in your laboratory require more frequent calibration, in replicates of 2 at two separate times per day for 20 days. use of controls to verify test results, follow those procedures. Representative data are shown in the following table: To achieve maximum on-board reagent stability, more frequent use of Target Mean controls may be required to monitor reagent performance within the Control Concentration Conc. Value Within Run Total Run same lot. Level (ng/mL) (ng/mL) SD %CV SD %CV Low 500 550.16 38.00 6.91 54.96 9.99 Ensure that assay control values are within the concentration ranges Medium 1500 1553.74 82.29 5.30 123.92 7.98 specified in the package insert. Refer to the REAGENTS, CONTROLS High 3000 3120.78 192.38 6.16 240.15 7.70 section of this package insert for XSYSTEMS Multiconstituent Control ranges for AxSYM assays.

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 5 99/17/2008/17/2008 11:38:5411:38:54 AAMM Precision at the cut-off concentration of 300 ng/mL in addition to the above The following compounds do not cross-react above the sensitivity control concentrations typically yield %CV of less than 10.1% when using (30.00 ng/mL) of the AxSYM Cocaine Metabolite assay (Compounds tested the NCCLS Protocol EP5-T2. at 100,000 ng/mL, unless otherwise indicated):

Accuracy By Recovery Acetaminophen Two sets of calibrators and controls were prepared by adding known Acetylsalicylic Acid Methadone Primary quantities of benzoylecgonine to human urine and AxSYM Solution 4 (Line Alprazolam Metabolite (EDDP) Diluent) to levels of 300, 500, 1000, 1500, 2000, 3000 and 5000 ng/mL. The d- Amobarbital 3,4-methylenedioxy- analyzer was calibrated with urine calibrators and both sets of calibrators (MDA) and controls were assayed relative to this calibration. Percent recovery = d,l-amphetamine 3,4-methylenedioxyethyl- 100 x (“concentration in Solution 4” divided by “concentration in urine”). Ampicillin amphetamine (MDE) Representative data are shown in the following table: Aspartame 3,4-methylenedioxymeth- Benzocaine amphetamine (MDMA) Added Concentration Concentration Benzoic Acid Concentration in urine in Solution 4 Percent (%) * Buprenorphine Methyprylon (ng/mL) (ng/mL) (ng/mL) Recovery Butabarbital Morphine 300 321.00 293.14 91.32 * Nalidixic Acid 500 521.53 520.70 99.84 Calcium Hypochlorite Naloxone 1000 941.23 979.39 104.05 Chloramphenicol Naltrexone 1500 1642.85 1553.67 94.57 Chlordiazepoxide * Naproxen 2000 2131.79 2128.99 99.87 Chloroquine Niacinamide * Chlorpheniramine 3000 3028.27 3009.57 99.38 Cholesterol * Norfloxacin 5000 4613.44 4740.87 102.76 * Ciprofloxacin * Oxolinic Acid Average Recovery: 98.82 ± 4.5% * Cinoxacin Oxycodone Sensitivity Clindamycin * Oxymorphone Codeine * Penicillin G The sensitivity of the AxSYM Cocaine Metabolite assay was calculated Diazepam Phenethylamine to be 30.00 ng/mL. This sensitivity is defined as the lowest measurable Digoxin Phenobarbital concentration which can be distinguished from zero with at least 95% Dihydrocodeine Phenothiazine confidence. Dihydromorphine Specificity Phenylbutazone # Ecgonine Methyl Ester Cross-reactivity was tested for cocaine metabolites. The following Phenyltoloxamine compounds cross-react above the sensitivity (30.00 ng/mL) of the AxSYM Epinephrine * Piromidic Acid Cocaine Metabolite assay: * Erythromycin # Progesterone Estriol * Promethazine Concentration * Fenoprofen Prolintane Compound Tested (ng/mL) * Furosemide Cocaine 10,000 Gentisic Acid Quinine Ecgonine 10,000 Glutethimide Salicyclic Acid Guaiacol Glyceryl Ether Secobarbital Serotonin Histamine Sulindac Hydralazine Tetracycline Hydrocodone 11-Nor-delta-9-tetrahydro- Hydromorphone cannabinol-9-carboxylic * Ibuprofen Acid Isoproterenol * Tolbutamide Ketoprofen Trifluoperazine Lovastatan Trimethoprim Melanin Meperidine * Vincristine # Tested at 10,000 ng/mL * Tested at 1,000,000 ng/mL

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 6 99/17/2008/17/2008 11:38:5411:38:54 AAMM Interference 3000 ng/mL n=100 TDx Pos TDx Neg GC/MS Pos GC/MS Neg The compounds listed below, added to human urine, resulted in less than AxSYM Pos 27 0 27 0 10% error in detecting added drug when assayed with the AxSYM Cocaine AxSYM Neg 0 73 48 25 Metabolite assay. CONCORDANCE Compound Concentration AxSYM vs. TDx = 100% Tested AxSYM vs. GC/MS = 52% Acetone 1 g/dL AxSYM “Positive” = Concentration greater than or equal to Ascorbic Acid 1.5 g/dL the cut-off, 300, 1000 or 3000 ng/mL of Bilirubin 0.25 mg/dL Benzoylecgonine. Creatinine 500 mg/dL TDx “Positive” = Concentration greater than or equal to Ethanol 1 g/dL the cut-off, 300, 1000 or 3000 ng/mL of Glucose 2 g/dL Benzoylecgonine. Hemoglobin (lysed red blood cells) 115 mg/dL Oxalic Acid 100 mg/dL GC/MS “Positive” = Concentration greater than or equal to Riboflavin 7.5 mg/dL 300 ng/mL of Benzoylecgonine. Sodium Chloride 6 g/dL * = Sample was evaluated on the AxSYM to be 285.08 ng/mL and Total Protein 0.05 g/dL GC/MS to be 379.00 ng/mL. Urea 6 g/dL **= Samples were evaluated on the AxSYM to be within the range of 300.65 - 498.80 ng/mL and on GC/MS to be within the range The presence of detergents in samples potentially interferes with of 170.00 - 290.00 ng/mL. immunoassay results. Bleach (hypochlorite) is a strong oxidizing agent. As a consequence, BIBLIOGRAPHY bleach may cause oxidation of some analytes, thus reducing the amount 1. Hawks RL. Analytical Methodology. In: Chiang CN, Hawks RL, eds. available for analysis. This may result in lower analytic results, regardless Urine testing for drugs of abuse. National Institute on Drug Abuse of the methodology.14 (NIDA). Research Monograph 73. Rockville, MD: Department of Health and Human Services, 1986; 35-8. There is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results. 2. Baselt RC. Urine drug screening by immunoassay: Interpretation of results. In: Baselt RC, ed. Advances in analytical toxicology. Foster Accuracy By Correlation with Reference Assays City, CA: Biomedical Publications, 1984; Vol. 1: 81-123. The AxSYM Cocaine Metabolite assay was evaluated for concordance to 3. Goldfrank L, Lewin N, Weisman R, Flomenbaum N, eds. Toxicologic TDx® and GC/MS by assaying drug-free and drug containing urine samples emergencies: A comprehensive handbook in problem solving. 2nd for benzoylecgonine. Samples were analyzed on-site at Abbott Laboratories Edition. New York, NY: Appleton Century-Crofts, 1982; 179-88. on AxSYM and TDx. GC/MS analysis of these samples was performed at a reference laboratory in Tennessee and on-site at Abbott Laboratories. 4. Ambre J, Fischman M, Ruo T. Urinary excretion of ecgonine Concordance is related to selected cut-off. The performance of AxSYM methyl ester, a major metabolite of cocaine in humans. J Anal Tox Cocaine Metabolite assay was evaluated at several cut-off levels (cut-off 1984; 8: 23-5. is the level above which the AxSYM flags a sample as positive for the 5. Van Dyke C, Byck R, Barash P, Jatlow P. Urinary excretion of desired analyte). The cut-off for GC/MS methodology is chosen by the immunologically reactive metabolite(s) after intranasal administration reference laboratory. of cocaine, as followed by enzyme immunoassay. Clin Chem Concordance = [(TP + TN) 1977; 23: 241-4. x 100 (TP + FP + TN + FN)] 6. Jatlow PI, Van Dyke C, Barash P, Byck R. Measurement of benzoylecgonine and cocaine in urine, separation of various TP = True positives cocaine metabolites using reversed-phase high-performance liquid TN = True negatives chromatography. J Chromatog 1978; 152: 115-21. FP = False positives 7. US Department of Labor, Occupational Safety and Health FN = False negatives Administration, 29 CFR Part 1910.1030, Bloodborne pathogens.

300 ng/mL n=100 TDx Pos TDx Neg GC/MS Pos GC/MS Neg 8. US Department of Health and Human Services. Biosafety in AxSYM Pos 83 2 74 11** Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: AxSYM Neg 1 14 1* 14 US Government Printing Office; January 2007. CONCORDANCE 9. World Health Organization. Laboratory Biosafety Manual. 3rd ed. AxSYM vs. TDx = 97% Geneva: World Health Organization; 2004. AxSYM vs. GC/MS = 88% 10. Clinical and Laboratory Standards Institute. Protection of Laboratory 1000 ng/mL n=100 TDx Pos TDx Neg GC/MS Pos GC/MS Neg Workers from Occupationally Acquired Infections: Approved Guideline AxSYM Pos 45 1 46 0 -Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and AxSYM Neg 2 52 29 25 Laboratory Standards Institute; 2005. CONCORDANCE 11. National Institute on Drug Abuse and Department of Health and Human AxSYM vs. TDx = 97% Services. The NIDA Guidelines. Subpart B, Section 2.4 (c, h). Federal AxSYM vs. GC/MS = 71% Register, Vol. 59, No. 110, 9 June 1994.

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33B24-1C-20_Eng_ReIn.inddB24-1C-20_Eng_ReIn.indd 7 99/17/2008/17/2008 11:38:5411:38:54 AAMM 12. National Committee for Clinical Laboratory Standards. Urine Drug Testing in the Clinical Laboratory; Proposed Guideline. NCCLS Document T/DM8-P. Villanova, PA: NCCLS, 1993. 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 of Organic Synthesis. New York: John Wiley & Sons, Inc., 1967-84: Vols. 1-11.

AxSYM, XSYSTEMS and TDx are trademarks of Abbott Laboratories, Abbott Park, IL USA.

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