List Number. In Vitro Diagnostic Medical Device Lot Number. Store at 2-8 C Calibrator (A-F) Store at C. Consult instructions for use

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1 E Cocaine Metabolite 3B /R9 Cocaine Metabolite Customer Service United States: ABBOTT 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, 28 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 5-3 C Control Low, Medium, High (L, M, H) Consult instructions for use Sample Cups Manufacturer Reagent Pack 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 664 USA Printed in USA 3B24-C-2_Eng_ReIn.indd Colors: PMS 365 PMS 222 BLACK LE: Pam DTP: Scott 9/7/28 :38:48 AM

2 NAME Cocaine Metabolite INTENDED USE The AxSYM Cocaine Metabolite assay is a semi-quantitative reagent system for the detection of the primary urinary metabolite of Cocaine, benzoylecgonine in human urine. Measurements obtained are used as an aid in the diagnosis and treatment of cocaine use or abuse. The AxSYM Cocaine Metabolite assay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. SUMMARY AND EXPLANATION OF TEST The AxSYM Cocaine Metabolite assay utilizes Fluorescence Polarization Immunoassay (FPIA) technology. Refer to the AxSYM System Operations Manual, Section 3, under Principles of Operation for a discussion of this technology. Cocaine is a frequently abused drug. The drug is administered by nasal insufflation, intravenous injection or in the free base form as smoke inhalation. The urinary elimination of cocaine and its metabolite begins within 2 minutes of its intranasal administration. 2-6 A single dose is excreted in a 24-hour urine as cocaine ( - 9 %), benzoylecgonine (35-54 %), ecgonine methyl ester (32-49 %) and ecgonine (not quantitated). 2 The Cocaine Metabolite assay is designed to perform at a variety of commonly used cut-off levels. The analyzer has been factory set at 3. ng/ml. NIDA recommends a 3 ng/ml cut-off for screening assays detecting Cocaine Metabolite (Federal Register June 9, 994). Abbott Laboratories recommends the use of this cut-off, if appropriate for your client population. To configure the cut-off in your laboratory refer to the INSTRUMENT PROCEDURE section in this insert. Selection of the cut-off value should be based on review of the laboratory s and it s clients needs, sensitivity of available confirmation methods and the sensitivity and cross-reactivity data of the assay itself. BIOLOGICAL PRINCIPLES OF THE PROCEDURE The AxSYM Cocaine Metabolite assay is based on Fluorescence Polarization Immunoassay (FPIA) technology. The AxSYM Cocaine Metabolite Reagents and sample are pipetted in the following sequence: SAMPLING CENTER Sample and all AxSYM Cocaine Metabolite Reagents required for one test are pipetted by the sampling probe into various wells of a Reaction Vessel (RV). Sample and Solution 4 (Line Diluent) are pipetted into one well of the RV. The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center with the processing probe. PROCESSING CENTER An aliquot of the predilution mixture, pretreatment/antibody mixture and Solution 4 (Line Diluent) are transferred to the cuvette of the RV. After an incubation period, a second aliquot of the antibody/pretreatment mixture, Cocaine Metabolite Fluorescein Tracer and a second aliquot of the predilution mixture are transferred to the cuvette. Cocaine Metabolite from the sample and the AxSYM Cocaine Metabolite Fluorescein Tracer compete for binding sites on the antibody molecule. The intensity of polarized fluorescent light is measured by the FPIA optical assembly. For further information, refer to the AxSYM System Operations Manual, Section 3. REAGENTS REAGENT PACK, TESTS AxSYM Cocaine Metabolite Reagent Pack (3B24-2) Bottle (5.4 ml) < 5% Cocaine Metabolite Antiserum (Sheep) in buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle ). Bottle (4. ml) Pretreatment Solution, buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 2). Bottle (5.3 ml) <.% Cocaine Metabolite Fluorescein Tracer in buffer with surfactant and protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 3). 3B24-99 includes an AxSYM Cocaine Metabolite Reagent Pack ( Tests) and reaction vessels ( each). 3B24-2 includes these items for international shipments. CALIBRATORS XSYSTEMS Cocaine Metabolite Calibrators (967-6) 6 Bottles (4 ml A, 2.5 ml each B-F) of XSYSTEMS Cocaine Metabolite Calibrators. Calibrator A contains human urine and Calibrators B through F contain benzoylecgonine prepared in human urine to yield the following concentrations: Benzoylecgonine Bottle (ng/ml) (μmol/l) Preservative: Sodium Azide. CONTROLS XSYSTEMS Multiconstituent Controls (9687-2) Bottles each of Low, Medium and High (4.5 ml each) prepared in human urine diluent to read within the following ranges: Benzoylecgonine Range Bottle (ng/ml) (μmol/l) (ng/ml) (μmol/l) Preservative: Sodium Azide. The calibrators and controls are matched to an Abbott internal reference standard. This internal reference standard is manufactured by gravimetric methods using benzoylecgonine anhydrous (not less than purity 99%) at each concentration level. OTHER REAGENTS AxSYM Probe Cleaning Solution (9A35-5) 2 Bottles (22 ml each) AxSYM Probe Cleaning Solution containing 2% Tetraethylammoniumhydroxide (TEAH). 2 3B24-C-2_Eng_ReIn.indd 2 9/7/28 :38:53 AM

3 Solution 4 (Line Diluent) (8A46) Bottle ( L) Solution 4 (Line Diluent) containing. M Phosphate Buffer. Preservatives: Sodium Azide and Antimicrobial Agent. WARNINGS AND PRECAUTIONS For In Vitro Diagnostic Use. SAFETY PRECAUTIONS CAUTION: This product contains material derived from human urine. Human urine sourced from healthy adults has not been shown to be a source of infectious agents, however, it is recommended that all human samples and reagents should be handled as potentially infectious material. Use precautions as specified in the OSHA Standard on Bloodborne Pathogens or other equivalent biosafety guidelines. 7,8,9, This product contains sodium azide; for a specific listing, refer to the REAGENTS section. Contact with acids liberates very toxic gas. This material and its container must be disposed of in a safe way. For product not classified as dangerous per European Directive 999/45/EC as amended - Safety data sheet available for professional user on request. HANDLING PRECAUTIONS Do not use Reagent Packs beyond the expiration date or the maximum on-board stability. A maximum of 336 cumulative hours on-board the AxSYM System are available when using assay file version 4 or higher (located on the Abused Drugs/Toxicology Assay Disk 3D54-2 or higher). A maximum of 2 cumulative hours on-board the AxSYM System are available when using assay file version 3 (located on the Abused Drugs/Toxicology Assay Disk 3D54-; or assay version 2 located on the Cocaine Metabolite Assay Disk 9B65-2). Do not mix reagents from different reagent packs regardless of lot number. Refer to the AxSYM System Operations Manual, Sections 7 and 8, for a more detailed discussion of safety and handling precautions during system operation. STORAGE INSTRUCTIONS The AxSYM Cocaine Metabolite Reagent Pack, XSYSTEMS Cocaine Metabolite Calibrators and XSYSTEMS Multiconstituent Controls must be stored at 2-8 C. They may be used immediately after removing them from the refrigerator. Calibrators and Controls should be returned to 2-8 C storage immediately after use. Reagents are stable until the expiration date when stored and handled as directed. The AxSYM Cocaine Metabolite Reagent Pack may be on-board the AxSYM System for a maximum of 336 cumulative hours when using the assay file version 4 or higher located on the Abused Drugs/Toxicology Assay Disk 3D54-2 or higher; for example 42, eight-hour shifts. The AxSYM Cocaine Metabolite Reagent Pack may be on-board the AxSYM System for a maximum of 2 cumulative hours when using the assay file version 3 located on the Abused Drugs/Toxicology Assay Disk 3D54- or the assay version 2 located on the Cocaine Metabolite Assay Disk 9B65-2, for example 4, 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. The AxSYM Probe Cleaning Solution and Solution 4 (Line Diluent) must be stored at 5-3 C. INSTRUMENT PROCEDURE Assay File Installation The AxSYM Cocaine Metabolite Assay File must be installed on the AxSYM System from one of the following software disks, prior to performing Cocaine Metabolite assays: 9B65-2 or 3D54- (2 hours on-board Stability) 3D54-2, or higher (336 hours on-board Stability) Refer to the AxSYM System Operations Manual, Section 2, for proper installation procedures. AxSYM Cocaine Metabolite Assay Parameters The default values for the assay parameters used for the AxSYM Cocaine Metabolite assay are listed below. Assay parameters that can be edited contain a (>) symbol. These parameters can be displayed and edited according to the procedure in the AxSYM System Operations Manual, Section 2: Installation Procedures and Special Requirements. In order to obtain values for the parameters with an asterisk (), review the specific Assay Parameter screen. Press PRINT to print the assay parameters Assay Parameters Long Assay Name (English): Cocaine_Met Abbrev Assay Name (English): Cocaine Assay Number: 5 Assay Version: Calibration Version: Assay File Revision: Assay Enabled > ON Assay Type: FPIA Standard Cal Reps > 2 Cal A :. Cal B : 3. Cal C :. Cal D : 2. Cal E : 3. Cal F : 5. Default Dilution Protocol > UNDILUTED Default Calibration Method > Standard Cal Selected Result Units > ng/ml Selected Result Decimal Places > 2 Blank I-Max background intensity: Min Tracer-Min net intensity: Low Limit - Normal/Therapeutic Range lower limit >. High Limit - Normal/Therapeutic Range upper limit >. Low Extreme Value >. High Extreme Value >. Interpretation Option to use > Hold results with POS interpretation > OFF Hold results with NEG interpretation > OFF Low Range Undiluted: High Range Undiluted: Positive Interpretation Cutoff > 3. Negative Interpretation Cutoff > 3. NOTE: Parameter 45 can be edited to the alternate result unit μg/ml or μmol/l. 3 3B24-C-2_Eng_ReIn.indd 3 9/7/28 :38:53 AM

4 The AxSYM Cocaine Metabolite values available for parameter #8 (Interpretation Option to use) are: POS Interp NEG Interp GRY Interp. POSITIVE NEGATIVE NONE 2. NONE NONE NONE Refer to the AxSYM System Operations Manual for a detailed description of Instrument Procedures. Selection of a cut-off AxSYM Drugs of Abuse/Toxicology Assay Disk 3D54-, or higher, installed on AxSYM System Software Version 3., or higher, provides the ability to edit the Interpretation range. Assay Parameters 6 Positive Interpretation Cutoff and 7 Negative Interpretation Cutoff have a default setting of 3. ng/ml. Any result at or above the Cut-off will provide a POSITIVE interpretation along with the numerical value. Any result below the Cut-off will provide a NEGATIVE interpretation along with the numerical value. This assay parameter may be edited to a Cut-off appropriate for your client population. When using interpretations, Assay Parameters 6 and 7 MUST be edited to the same value to avoid an incorrect interpretation being provided for a result. Refer to the AxSYM System Operations Manual, Section 2, for further 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 (- C or colder) if not analyzed within 48 hours.,2 Frozen samples must be thawed and mixed thoroughly prior to analysis. Sodium azide (.%), boric acid (.%) and sodium fluoride (.3%) 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 Cocaine Metabolite 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. SAMPLE VOLUME The sample volume required to perform a single cocaine metabolite test on the AxSYM System varies depending on the type of sample container used. For sample cups, a ROUTINE test requires 5 μl and a STAT test requires 94 μl. For every additional cocaine metabolite test performed (ROUTINE or STAT) from the same container, an additional 44 μl of sample is required. The sample cup minimum volumes for both STAT and ROUTINE tests are calculated by the AxSYM System. They are displayed on the Order screen 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 Orderlist Report are not available. Refer to the AxSYM System Operations Manual, Section 5, for a description of the Host Order Query option. If the assay is configured for auto retest, the additional sample volume needed for the retest will not be displayed on the Order screen at the time the test(s) is(are) ordered. Therefore, the total sample volume should include an additional 44 μl of sample. 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. AxSYM COCAINE METABOLITE PROCEDURE Materials Provided 3B24-99 AxSYM Cocaine Metabolite Reagent Kit, containing: AxSYM Cocaine Metabolite Materials Required But Not Provided XSYSTEMS Cocaine Metabolite Calibrators XSYSTEMS Multiconstituent Controls 8A46 9A35-5 AxSYM 8A76- Pipettes/Pipette tips (optional) to deliver the volume specified on the order screen CAUTION: When manually dispensing sample into sample cups, verify that dispensing equipment does not introduce cross contamination and delivers the specified sample volume. Use a separate pipette tip for each sample. For optimal performance it is important to follow the routine maintenance procedures defined in the AxSYM System Operations Manual, Section 9. If your laboratory requires more frequent maintenance, follow those procedures. Assay Procedure Sections 5 and 6 of the AxSYM System Operations Manual can be removed for use at the instrument. They contain detailed steps for performing assay calibration and sample testing procedures. Prior to ordering tests, confirm that the System inventory of Reaction Vessels and Solution 4 (Line Diluent) is sufficient. The Orderlist Report contains sample placement information and STAT sample volume requirements for all ordered tests. It is recommended that this report be referenced when loading samples into sample segments. When using Host Order Query, the Orderlist Report is not available. Refer to AxSYM System Operations Manual, Section 5, for a description of the Host Order Query option. CAUTION: When operating the AxSYM System, always observe the following: The System status must be WARMING, PAUSED, READY, or STOPPED before adding or removing sample segments, reagent packs or Reaction Vessels (RV s). An Error Code 566 Matrix cell not detected, trap door, processing center may be displayed when the instrument homes the motors. If performing only FPIA (and/or REA ) assays, select OK to proceed with testing. Do not open the Interior Waste Door or the AxSYM Processing Center Cover while any test is in process. If opened, all processing will stop. Tests in process will be terminated and must be repeated. When testing is completed, it is recommended that samples and the AxSYM Cocaine Metabolite Reagent Pack are removed from the Sampling Center to maximize the on-board reagent pack use. Store Reagent Pack at 2-8 C. 4 3B24-C-2_Eng_ReIn.indd 4 9/7/28 :38:54 AM

5 SAMPLE DILUTION PROCEDURES CAUTION: The automated dilution protocol, as described in the AxSYM System Operations Manual, Section 5, CANNOT BE USED with the AxSYM Cocaine Metabolite assay. Manual Dilution Protocol If a numerical value is desired for patient samples reported as > 5 ng/ml, the urine sample may be manually diluted with XSYSTEMS Cocaine Metabolite Calibrator A and repeated on the AxSYM System. The concentration reported by the AxSYM System must be multiplied by the manual dilution factor to obtain the final sample concentration. Final Sample = Reported x Manual Dilution Factor Manual Dilution Factor = (Volume of Sample + Volume of Dilution Reagent) Volume of Sample QUALITY CONTROL PROCEDURES CALIBRATION The AxSYM Cocaine Metabolite assay must be calibrated using a Standard Calibration (6-point) procedure. To review the detailed results of a calibration curve, refer to Section 6 of the AxSYM System Operations Manual. Standard Calibration To perform an AxSYM Cocaine Metabolite Standard Calibration, test XSYSTEMS Cocaine Metabolite Calibrators A, B, C, D, E, and F in duplicate. A single sample of all levels of controls must be tested to evaluate the assay calibration. Once the AxSYM Cocaine Metabolite calibration is accepted and stored, all subsequent samples may be tested without further calibration unless: A reagent pack with a new lot number is used. Control values are out of their specific range. Refer to the AxSYM System Operations Manual, Section 6, for: Setting up an assay calibration When recalibration may be necessary Calibration Verification The AxSYM System verifies that the results of an assay calibration meet the specifications assigned to selected validity parameters. An error message occurs when the calibration fails to meet a specification. Refer to the AxSYM System Operations Manual, Section, for an explanation of the corrective actions for the error code. Refer to the AxSYM System Operations Manual, Appendices, for an explanation of the calibration validity parameters that may be used by the AxSYM System. Operator Verification An acceptable Cocaine Metabolite calibration curve should have all control values within the acceptable ranges. QUALITY CONTROL The recommended control requirement for an AxSYM Cocaine Metabolite assay is a single sample of at least two control levels tested once every 24 hours, each day of use. Controls may be placed in any position in the Sample Carousel. If the quality control procedures in your laboratory require more frequent use of controls to verify test results, follow those procedures. To achieve maximum on-board reagent stability, more frequent use of controls may be required to monitor reagent performance within the same lot. Ensure that assay control values are within the concentration ranges specified in the package insert. Refer to the REAGENTS, CONTROLS section of this package insert for XSYSTEMS Multiconstituent Control ranges for AxSYM assays. INDICATIONS OF INSTABILITY OR DETERIORATION OF REAGENTS When a control value is out of the specified range, it may indicate deterioration of the reagents or errors in technique. Associated test results may be invalid and require retesting. Assay recalibration may be indicated. Refer to the AxSYM System Operations Manual, Section, for further troubleshooting information. The AxSYM System has a capability to generate a Levey-Jennings plot of each assay s quality control performance. Refer to the AxSYM System Operations Manual, Section 5, for further information. At the discretion of the laboratory, selected quality control rules may be applied to the quality control data. RESULTS The AxSYM Cocaine Metabolite assay is a semi-quantitative reagent system. The AxSYM Cocaine Metabolite assay provides only a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. A Four Parameter Logistic Fit Method (4PLC, Y weighted) is used to generate the AxSYM Cocaine Metabolite standard curve. The calibration curve is stored in memory and concentrations of drug in controls and unknown samples are calculated from this curve using polarization values generated. Alternate Units The default result unit for AxSYM Cocaine Metabolite is ng/ml. When selecting the alternate result unit, μmol/l, the conversion factor used by the AxSYM System is When selecting the alternate result unit μg/ml, the conversion factor used by the AxSYM System is.. Flags Some results may contain information in the Flags field. For a description of the flags that may appear in this field, refer to the AxSYM System Operations Manual, Sections and 2. LIMITATIONS OF THE PROCEDURE As with all analyte determinations, the Cocaine Metabolite value should be used in conjunction with information available from clinical evaluation and other diagnostic procedures. Urine samples with a background intensity greater than the allowable value are flagged with error code 65 Invalid test results, background intensity too high, (#). These samples must NOT BE DILUTED AND RERUN. An alternative analysis method must be used on these samples. EXPECTED VALUES s of drugs and/or metabolite(s) detected in urine have not been correlated to drug levels in the bloodstream nor with degree of impairment. The presence of a drug and/or metabolite(s) in urine is only an indication of previous drug exposure. 2 SPECIFIC PERFORMANCE CHARACTERISTICS Precision Precision was determined as described in the National Committee for Clinical Laboratory Standards (NCCLS) Protocol EP5-T2. 3 A three member urine panel was assayed, using a single lot of reagents and a single calibration, in replicates of 2 at two separate times per day for 2 days. Representative data are shown in the following table: Target Mean Control Conc. Value Within Run Total Run Level (ng/ml) (ng/ml) SD %CV SD %CV Low Medium High B24-C-2_Eng_ReIn.indd 5 9/7/28 :38:54 AM

6 Precision at the cut-off concentration of 3 ng/ml in addition to the above control concentrations typically yield %CV of less than.% when using the NCCLS Protocol EP5-T2. Accuracy By Recovery Two sets of calibrators and controls were prepared by adding known quantities of benzoylecgonine to human urine and AxSYM Solution 4 (Line Diluent) to levels of 3, 5,, 5, 2, 3 and 5 ng/ml. The analyzer was calibrated with urine calibrators and both sets of calibrators and controls were assayed relative to this calibration. Percent recovery = x ( concentration in Solution 4 divided by concentration in urine ). Representative data are shown in the following table: Added (ng/ml) in urine (ng/ml) in Solution 4 (ng/ml) Percent (%) Recovery Average Recovery: ± 4.5% Sensitivity The sensitivity of the AxSYM Cocaine Metabolite assay was calculated to be 3. ng/ml. This sensitivity is defined as the lowest measurable concentration which can be distinguished from zero with at least 95% confidence. Specificity Cross-reactivity was tested for cocaine metabolites. The following compounds cross-react above the sensitivity (3. ng/ml) of the AxSYM Cocaine Metabolite assay: Compound Cocaine Ecgonine Tested (ng/ml),, The following compounds do not cross-react above the sensitivity (3. ng/ml) of the AxSYM Cocaine Metabolite assay (Compounds tested at, ng/ml, unless otherwise indicated): # Acetaminophen Acetylsalicylic Acid Alprazolam Amitriptyline Amobarbital Amoxicillin d,l-amphetamine Ampicillin Aspartame Benzocaine Benzoic Acid Buprenorphine Butabarbital Caffeine Calcium Hypochlorite Chloramphenicol Chlordiazepoxide Chloroquine Chlorpheniramine Cholesterol Ciprofloxacin Cinoxacin Clindamycin Codeine Diazepam Digoxin Dihydrocodeine Dihydromorphine Diphenhydramine Ecgonine Methyl Ester Ephedrine Epinephrine Erythromycin Estriol Fenoprofen Furosemide Gentisic Acid Glutethimide Guaiacol Glyceryl Ether Haloperidol Histamine Hydralazine Hydrocodone Hydromorphone Ibuprofen Isoproterenol Ketamine Ketoprofen Lovastatan Melanin Meperidine # Tested at, ng/ml Tested at,, ng/ml # Methadone Methadone Primary Metabolite (EDDP) d-methamphetamine 3,4-methylenedioxyamphetamine (MDA) 3,4-methylenedioxyethylamphetamine (MDE) 3,4-methylenedioxymethamphetamine (MDMA) Methylphenidate Methyprylon Morphine Nalidixic Acid Naloxone Naltrexone Naproxen Niacinamide Nicotine Norfloxacin Oxolinic Acid Oxycodone Oxymorphone Penicillin G Phenethylamine Phenobarbital Phenothiazine Phentermine Phenylbutazone Phenylpropanolamine Phenyltoloxamine Piromidic Acid Progesterone Promethazine Prolintane Pseudoephedrine Quinine Salicyclic Acid Secobarbital Serotonin Sulindac Tetracycline -Nor-delta-9-tetrahydrocannabinol-9-carboxylic Acid Theophylline Tolbutamide Trifluoperazine Trimethoprim Tyramine Vincristine 6 3B24-C-2_Eng_ReIn.indd 6 9/7/28 :38:54 AM

7 Interference The compounds listed below, added to human urine, resulted in less than % error in detecting added drug when assayed with the AxSYM Cocaine Metabolite assay. Compound Acetone Ascorbic Acid Bilirubin Creatinine Ethanol Glucose Hemoglobin (lysed red blood cells) Oxalic Acid Riboflavin Sodium Chloride Total Protein Urea Tested m m m m m The presence of detergents in samples potentially interferes with immunoassay results. Bleach (hypochlorite) is a strong oxidizing agent. As a consequence, bleach may cause oxidation of some analytes, thus reducing the amount available for analysis. This may result in lower analytic results, regardless of the methodology. 4 There is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results. Accuracy By Correlation with Reference Assays The AxSYM Cocaine Metabolite assay was evaluated for concordance to TDx and GC/MS by assaying drug-free and drug containing urine samples for benzoylecgonine. Samples were analyzed on-site at Abbott Laboratories on AxSYM and TDx. GC/MS analysis of these samples was performed at a reference laboratory in Tennessee and on-site at Abbott Laboratories. Concordance is related to selected cut-off. The performance of AxSYM Cocaine Metabolite assay was evaluated at several cut-off levels (cut-off is the level above which the AxSYM flags a sample as positive for the desired analyte). The cut-off for GC/MS methodology is chosen by the reference laboratory. Concordance = [(TP + TN) (TP + FP + TN + FN)] x TP = True positives TN = True negatives FP = False positives FN = False negatives 3 ng/ml n= TDx Pos TDx Neg GC/MS Pos GC/MS Neg AxSYM Pos AxSYM Neg CONCORDANCE AxSYM vs. TDx = 97% AxSYM vs. GC/MS = 88% ng/ml n= TDx Pos TDx Neg GC/MS Pos GC/MS Neg AxSYM Pos AxSYM Neg CONCORDANCE AxSYM vs. TDx = 97% AxSYM vs. GC/MS = 7% 3 ng/ml n= TDx Pos TDx Neg GC/MS Pos GC/MS Neg AxSYM Pos AxSYM Neg CONCORDANCE AxSYM vs. TDx = % AxSYM vs. GC/MS = 52% AxSYM Positive = greater than or equal to the cut-off, 3, or 3 ng/ml of Benzoylecgonine. TDx Positive = greater than or equal to the cut-off, 3, or 3 ng/ml of Benzoylecgonine. GC/MS Positive = greater than or equal to 3 ng/ml of Benzoylecgonine. = Sample was evaluated on the AxSYM to be ng/ml and GC/MS to be 379. ng/ml. = Samples were evaluated on the AxSYM to be within the range of ng/ml and on GC/MS to be within the range of ng/ml. BIBLIOGRAPHY. 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, 986; Baselt RC. Urine drug screening by immunoassay: Interpretation of results. In: Baselt RC, ed. Advances in analytical toxicology. Foster City, CA: Biomedical Publications, 984; Vol. : Goldfrank L, Lewin N, Weisman R, Flomenbaum N, eds. Toxicologic emergencies: A comprehensive handbook in problem solving. 2nd Edition. New York, NY: Appleton Century-Crofts, 982; Ambre J, Fischman M, Ruo T. Urinary excretion of ecgonine methyl ester, a major metabolite of cocaine in humans. J Anal Tox 984; 8: Van Dyke C, Byck R, Barash P, Jatlow P. Urinary excretion of immunologically reactive metabolite(s) after intranasal administration of cocaine, as followed by enzyme immunoassay. Clin Chem 977; 23: Jatlow PI, Van Dyke C, Barash P, Byck R. Measurement of benzoylecgonine and cocaine in urine, separation of various cocaine metabolites using reversed-phase high-performance liquid chromatography. J Chromatog 978; 52: US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 9.3, Bloodborne pathogens. 8. 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; 24.. 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; 25.. 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., 9 June B24-C-2_Eng_ReIn.indd 7 9/7/28 :38:54 AM

8 National Committee for Clinical Laboratory Standards. Urine Drug Testing in the Clinical Laboratory; Proposed Guideline. NCCLS Document T/DM8-P. Villanova, PA: NCCLS, 993. 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, 992. Fieser, LF, Fieser M. Reagents of Organic Synthesis. New York: John Wiley & Sons, Inc., : Vols. -. AxSYM, XSYSTEMS and TDx are trademarks of Abbott Laboratories, Abbott Park, IL USA. ABBOTT Max-Planck-Ring Wiesbaden Germany Manufactured for Abbott Laboratories, Abbott Park IL by Abbott Diagnostics International, LTD. Barceloneta, Puerto Rico September, , 28 Abbott Laboratories 8 3B24-C-2_Eng_ReIn.indd 8 9/7/28 :38:54 AM