EBenzodiazepines 3B30-2034-5074/R9BenzodiazepinesCustomer ServiceUnited States: 1-877-4ABBOTTInternational: Call your Abbott RepresentativeThis 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 ChangesRevised August, 2008Key to symbols usedList NumberIn Vitro Diagnostic Medical DeviceLot NumberCalibrator (A-F) Control Low, Medium, High (L, M, H)Store at 2-8°CSample CupsConsult instructions for useAuthorized RepresentativeReaction VesselsStore at 15-30°C Expiration DateAssay NumberChecksumReagent PackManufacturerSee REAGENTS section for a full explanation of symbols used in reagent component naming.Abbott LaboratoriesDiagnostics DivisionAbbott Park, IL 600 USAPrinted in USA1NAMEBenzodiazepinesREAGENTSREAGENT PACK, 100 TESTSAxSYM Benzodiazepines Reagent Pack (3B30-20)*•1 Bottle (4.6 mL) < 5% Benzodiazepines Antiserum (Sheep) in buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 1)•1 Bottle (4.4 mL) Pretreatment Solution, Buffer with protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 2)•1 Bottle (5.3 mL) < 0.01% Benzodiazepines Fluorescein Tracer in buffer with surfactant and protein stabilizer. Preservative: Sodium Azide. (Reagent Bottle 3)*3B30-99 includes an AxSYM Benzodiazepines Reagent Pack(100 tests) and reaction vessels (100 each). 3B30-20 includes these items for international shipments.CALIBRATORSXSYSTEMS Benzodiazepines Calibrators (9674-02)6 Bottles (4 mL A, 2.5 mL each B-F) of XSYSTEMS Benzodiazepines Calibrators. Calibrator A contains human urine and Calibrators B through F contain nordiazepam prepared in human urine to yield the following concentrations:BottleNordiazepam Concentration(ng/mL)(nmol/L)00.00200738.234001476.458002952.901,2004429.352,4008858.70INTENDED USEThe AxSYM Benzodiazepines assay is a semi-quantitative reagent system for the detection of benzodiazepines and metabolites in human urine. Measurements obtained aid in the diagnosis and treatment of benzodiazepine use or abuse.The AxSYM Benzodiazepines 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 (G/MS) is the preferred confirmatory method.1 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 TESTThe AxSYM Benzodiazepines 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.Benzodiazepines are central nervous system depressants composed of over 20 compounds. They are used clinically as sedatives, hypnotics, anxiolytics, muscle relaxants, antiepileptics, and in the treatment of alcohol withdrawal.2 Benzodiazepines are extensively metabolized with half-lives ranging from 1 to 100 hours.3,4 Urine levels vary due to individual patient metabolic and excretion rates.The AxSYM Benzodiazepines 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. Abbott Laboratories recommends the use of this cut-off, if appropriate, for your client population. To configure your cut-off in your laboratory, refer to the INSTRUMENT PROCEDURE section of this insert.Selection of the cut-off value should be based upon review of the laboratory’s and their clients’ needs, sensitivity of available confirmation methods and the sensitivity and cross-reactivity data of the assay itself.Preservative: Sodium Azide.Abbott manufactures internal standards for Benzodiazepine using Nordazepam (USP Reference Standard). Benzodiazepine calibrators are manufactured gravimetrically and tested against these internal standards.CONTROLSXSYSTEMS Multiconstituent Controls (9687-12)2 Bottles each of Low, Medium and High (4.5 mL each) prepared in human urine diluent to read within the following ranges:NordiazepamBottleConcentration(ng/mL)(nmol/L)30060010001107.332214.663691.10Range(ng/mL)236.47 - 363.53457.98 - 742.02748.30 - 1251.70(nmol/L) 872.83 - 1341.82 1690.45 - 2738.87 2762.05 - 4620.15BIOLOGICAL PRINCIPLES OF THE PROCEDUREThe AxSYM Benzodiazepines assay is based on Fluorescence Polarization Immunoassay (FPIA) technology. The AxSYM Benzodiazepines Reagents and sample are pipetted in the following sequence:SAMPLING CENTER•Sample and all AxSYM Benzodiazepines 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) is transferred to the cuvette of the RV.•After an incubation period, a second aliquot of the antibody/pretreatment mixture, Benzodiazepines Fluorescein Tracer and a second aliquot of the predilution mixture is transferred to the cuvette.•Benzodiazepines from the sample and the AxSYM Benzodiazepines 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.Preservative: Sodium Azide.OTHER REAGENTSAxSYM Probe Cleaning Solution (9A35-05) 2 Bottles (220 mL each) AxSYM Probe Cleaning Solution containing 2% Tetraethylammoniumhydroxide (TEAH).Solution 4 (Line Diluent) (8A46) 1 Bottle (10 L) Solution 4 (Line Diluent) containing 0.1 M Phosphate Buffer. Preservatives: Sodium Azide and Antimicrobial Agent.WARNINGS AND PRECAUTIONSFor 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 these reagents and human specimens be handled as potentially infectious material. Use precautions as specified in the OSHA Standard on Bloodborne Pathogens or other appropriate biosafety guidelines.5,6,7,82•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 1999/45/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 1 00 400 or higher (located on the Abused Drugs/Toxicology Assay Disk 3D-02 or higher). A maximum of 112 cumulative hours on-board the AxSYM System are available when using assay file version 1 00 300 (located on the Abused Drugs/Toxicology Assay Disk 3D-01; or assay version 1 00 200 located on the Benzodiazepines assay disk 9B71-02).•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 Benzodiazepines Reagent Pack, XSYSTEMS Benzodiazepines 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 Benzodiazepines Reagent Pack may be on-board the AxSYM System for a maximum of 336 cumulative hours when using the assay file version 1 00 400 or higher located on the Abused Drugs/Toxicology Assay Disk 3D-02 or higher; for example 42, eight-hour shifts. The AxSYM Benzodiazepines Reagent Pack may be on-board the AxSYM System for a maximum of 112 cumulative hours when using the assay file version 1 00 300 located on the Abused Drugs/Toxicology Assay Disk 3D-01 or assay file version 1 00 200 located on the Benzodiazepines assay disk 9B71-02, 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 and appendices, for further information on tracking on-board time. The AxSYM Probe Cleaning Solution and Solution 4 (Line Diluent) must be stored at 15-30°C. 1 6 11 12 13 14 15 17 18 21 22 23 24 25 26 43 44 45 46 62 63 73 74 75 76 80 84 85 91 92 116 117 Assay ParametersLong Assay Name (English): Benzodiazepine_UAbbrev Assay Name (English): BenzosAssay Number: 533Assay Version: *Calibration Version: *Assay File Revision: *Assay Enabled > ONAssay Type: FPIAStandard Cal Reps > 2Cal A Concentration: 0.00Cal B Concentration: 200.00Cal C Concentration: 400.00Cal D Concentration: 800.00Cal E Concentration: 1200.00Cal F Concentration: 2400.00Default Dilution Protocol > UNDILUTEDDefault Calibration Method > Standard CalSelected Result Concentration Units > ng/mLSelected Result Decimal Places > 2Blank I-Max background intensity: *Min Tracer-Min net intensity: *Low Limit - Normal/Therapeutic Range lower limit > 0.00High Limit - Normal/Therapeutic Range upper limit > 0.00Low Extreme Value > 0.00High Extreme Value > 0.00Interpretation Option to use > 1Hold results with POS interpretation > OFFHold results with NEG interpretation > OFF Low Range Undiluted: 0.00High Range Undiluted: *Positive Interpretation Cutoff > 200.00Negative Interpretation Cutoff > 200.00NOTE: Parameter 45 can be edited to the alternate result unit μg/mL or nmol/L. The AxSYM Benzodiazepines values available for parameter #80 (Interpretation Option to use) are:POS Interp1.2.POSITIVENONENEG InterpNEGATIVENONEGRY InterpNONENONERefer to the AxSYM System Operations Manual for a detailed description of Instrument Procedures.Selection of a Cut-offEditable Interpretation Cut-offAxSYM Drugs of Abuse/Toxicology assay disk 3D-02, or higher, installed on AxSYM System Software Version 3.0, or higher, provides the ability to edit the Interpretation range. Assay Parameters “116 Positive Interpretation Cutoff” and “117 Negative Interpretation Cutoff” have a default setting of 200.00 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 116 and 117 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.INSTRUMENT PROCEDUREAssay File InstallationThe AxSYM Benzodiazepines Assay File must be installed on the AxSYM System from one of the following software disks, prior to performing Benzodiazepines assays:•9B71-02 or 3D-01 (112 hours on-board Stability)•3D-02, or higher (336 hours on-board Stability)Refer to the AxSYM System Operations Manual, Section 2, for proper installation procedures.AxSYM BENZODIAZEPINES ASSAY PARAMETERSThe default values for the assay parameters used for the AxSYM Benzodiazepines 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.3SAMPLE 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.9,10 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 System 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 Benzodiazepines 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.•Refer to the AxSYM System Operations Manual, Section 5, for a detailed discussion of on-board sample storage constraints.SAMPLE VOLUMEThe sample volume required to perform a single benzodiazepines test on the AxSYM System varies depending on the type of sample container used. For sample cups, a ROUTINE test requires 150 μL and a STAT test requires μL. For every additional benzodiazepines test performed (ROUTINE or STAT) from the same container, an additional 39 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 the additional 39 μL of sample.Refer to the AxSYM System Operations Manual, Section 5, for sample volume requirements in primary or aliquot tubes and calibrators/control requirements for multiple reagent lots.Assay ProcedureSections 5 and 6 of the AxSYM System Operations Manual 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 the 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 (RVs).•An “Error Code 5066 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 Benzodiazepines Reagent Pack are removed from the Sampling Center to maximize the on-board reagent pack use. Store Reagent Pack at 2-8°C.SAMPLE DILUTION PROCEDURESCAUTION: The automated dilution protocol, as described in the AxSYM System Operations Manual, Section 5, CANNOT BE USED with the AxSYM Benzodiazepines assay.Manual Dilution ProtocolIf a numerical value is desired for patient samples reported as > 2400 ng/mL, the urine sample may be manually diluted with XSYSTEMS Benzodiazepines 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 SampleConcentration = Reported Concentration x Manual Dilution FactorManualDilution Factor =(Volume of Sample + Volume of Dilution Reagent)Volume of SampleAxSYM BENZODIAZEPINES PROCEDUREMaterials Provided•3B30-99 AxSYM Benzodiazepines Reagent Kit, containing:AxSYM Benzodiazepines 100 Materials Required But Not Provided•9674-02 •9687-12 XSYSTEMS Benzodiazepines Calibrators XSYSTEMS Multiconstituent ControlsQUALITY CONTROL PROCEDURESCALIBRATIONThe AxSYM Benzodiazepines assay must be calibrated using a Standard Calibration (6 - point) procedure.Standard CalibrationTo perform an AxSYM Benzodiazepines Standard Calibration, test XSYSTEMS Benzodiazepines 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 Benzodiazepines 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•8A46 AxSYM •9A35-05 •8A76-01 •Pipettes/Pipette tips (Optional) to deliver the volume specified on the order screenCAUTION:•When manually dispensing sample into sample cups, verify that the 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.4The 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 10, 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 Benzodiazepines calibration curve should have all control values within the acceptable ranges.QUALITY CONTROL
The recommended control requirement for an AxSYM Benzodiazepines 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 REAGENTSWhen a Benzodiazepines 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 10, Subsection: Observed Problems, 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.
LIMITATIONS OF THE PROCEDURE
As with all analyte determinations, the benzodiazepines 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 “1065 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
Concentrations 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.11
SPECIFIC PERFORMANCE CHARACTERISTICS
Precision
Precision was determined as described in National Committee for Clinical Laboratory Standards (NCCLS) Protocol EP5-T2.12 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 20 days. Data from this study yielded %CV of less than 10%. Representative data follow:
ControlValueLowMediumHigh
TargetConcentration(ng/mL) 300 6001000
MeanConc. Value(ng/mL)315.19636.55962.78
WithinRunSD%CV 7.632.4217.382.7333.413.47
Total Run
SD%CV 7.952.5219.603.0834.953.63
Accuracy By Recovery
Two sets of calibrators and controls were prepared by adding
known quantities of nordiazepam to human urine and AxSYM Solution 4 (Line Diluent) to levels of 200, 300, 400, 600, 800, 1000, 1200 and 2400 ng/mL. The analyzer was calibrated with urine calibrators and both sets of calibrators and controls were assayed relative to this calibration. Percent recovery = 100 x (“concentration in Solution 4 (Line Diluent)” divided by “concentration in urine”). Representative data follow.
AddedConcentration(ng/mL) 200.00 300.00 400.00 600.00 800.001000.001200.002400.00
Concentrationin urine(ng/mL) 200.98 276.70 380.51 578.39 794.451020.681158.002185.29
Concentrationin Solution 4(ng/mL) 197.96 238.80 331.14 533.86 760.031038.291122.912183.56
Percent (%) Recovery 98.50 86.30 87.03 92.30 95.67101.73 96.97 99.92
RESULTS
The AxSYM Benzodiazepines assay is a semi-quantitative reagent system. The AxSYM Benzodiazepines 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 Benzodiazepines standard calibration 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 Result Units
The default result unit for AxSYM Benzodiazepines is ng/mL. When selecting the alternate result unit, nmol/L, the conversion factor used by the AxSYM System is 3.6911. When selecting the alternate result unit, μg/mL, the conversion factor used by the AxSYM System is 0.001.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 1 and 2.
Average Recovery: 94.8 ± 5.8%Sensitivity
The sensitivity of the AxSYM Benzodiazepines assay was calculated to be 40.00 ng/mL. This sensitivity is defined as the lowest measurable concentration which can be distinguished from zero with at least 95% confidence.
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Specificity
Cross-reactivity was tested for the commonly used benzodiazepines and metabolites. The following compounds cross-react above the sensitivity (40.00 ng/mL) of the AxSYM Benzodiazepines assay.
COMPOUND
AlprazolamBromazepamChlordiazepoxideClobazamClonazepamDemoxepam
DesalkylflurazepamDiazepamEstazolamFlunitrazepamFlurazepam
1-N-HydroxyethylflurazepamLorazepamLormetazepamMedazepam
Midazolam HydrochlorideNimetazepamNitrazepam
NorchlordiazepoxideOxazepamPrazepamTemazepamTriazolam
CONCENTRATION TESTED
(ng/mL)2002008001,0002004002002001002002002002001,000200200200200800200200200200
The following compounds do not cross-react above the sensitivity (40.00 ng/mL) of the AxSYM Benzodiazepines assay (Compounds tested at 100,000 ng/mL, unless otherwise indicated).
Acetaminophen Acetylsalicyclic acid Amitriptyline Amobarbital Amoxicillin Ampicillin Aspartame Benzocaine Benzoic Acid Benzoylecgonine Buprenorphine Butabarbital Caffeine Calcium Hypochlorite Chloramphenicol Chloroquine
Chlorpheniramine Cholesterol Clindamycin Codeine igoxin
ihydrocodeine ihydromorphine Ecgonine** Ephedrine* Epinephrine* Erythromycin Estriol
* Furosemide Gentisic Acid Glutethimide* Guaiacol Glyceryl Ether Haloperidol Histamine Hydralazine Hydrocodone Hydromorphone* Ibuprofen Isoproterenol* Ketamine Melanin Meperidine
Methadone Primary Metabolite (EDDP)
d-methamphetamine d,l-methamphetamine 3,4-Methylenedioxy- amphetamine (MDA)
3,4-Methylenedioxy-N-ethyl- amphetamine (MDE) 3,4-Methylenedioxymeth- amphetamine (MDMA) Methylphenidate Methyprylon Morphine Naloxone Naltrexone* Naproxen Niacinamide Nicotine Oxycodone Oxymorphone* Penicillin G* Phencyclidine Phenobarbital Phenothiazine
* Phenylpropanolamine# Progesterone* Promethazine** Pseudoephedrine Quinine Salicylic Acid Secobarbital Serotonin Sulindac Tetracycline
11-Nor-delta-9-tetrahydro- cannabinol-9-carboxylic Acid Theophylline Tolbutamide Trifluoperazine Trimethoprim Tyramine
Cross-reactivity was also tested with compounds that have similar chemical structure or are used concurrently. The following compounds cross-react above the sensitivity (40.00 ng/mL) of the AxSYM Benzodiazepines assay.
COMPOUNDBenzotropine
MethanesulfonateButyrophenoneClotrimazoleCocaineDimetacrine
DiphenhydramineFenoprofenFlurbiprofenFlufenamic acidFlumazenilGemfibrozilHydroxyzineIndomethacinIprindoleKetoprofenLovastatinLoxapine
Mefenamic AcidMethadone
MethotrimeprazineNorpropoxypheneOrphenadrineOxaprozin
PhendimetrazinePhenylbutazonePhenyltoloxamineProlintaneSertralineThenyldiamineTolmetinTrazodoneTripelennamine
CONCENTRATION TESTED
(ng/mL)1,000,000
1,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,000100,000100,000100,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,0001,000,000100,000
# Tested at 10,000 ng/mL* Tested at 1,000,000 ng/mL** Tested at 3,000,000 ng/mLInterference
DThe following compounds, added to human urine, resulted in less than D
10% error in detecting added drug when assayed with the AxSYM Benzodiazepines assay.Compound
AcetoneAscorbic AcidBilirubinCreatinineEthanolGlucose
Hemoglobin (lysed red blood cells)Oxalic AcidRiboflavin
Sodium ChlorideTotal ProteinUrea
Concentration Tested
1 g/dL 1.5 g/dL
0.25 mg/dL
500 mg/dL
1 g/dL
2 g/dL
115 mg/dL
100 mg/dL
7.5 mg/dL
6 g/dL
0.05 g/dL
6 g/dL
D
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.13
There is the possibility that other substances and/or factors not listed may interfere with the test and cause false results.
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Accuracy By Correlation with Reference AssaysThe AxSYM Benzodiazepines assay was evaluated for concordance to TDx and GC/MS by assaying drug-free and drug containing urine samples for benzodiazepines and metabolites. 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 Benzodiazepines 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 1004.Baselt RC, Cravey RH. Disposition of toxic drugs and chemicals in man. 3rd Edition. Chicago, IL: Year Book Medical Publications, Inc., 19;251, 483-4.US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 1910.1030, Bloodborne pathogens.US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office; January 2007.World Health Organization. Laboratory Biosafety Manual. 3rd ed. Geneva: World Health Organization; 2004.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.National Institute on Drug Abuse and Department of Health and Human Services. The NIA Guidelines. Subpart B, Section 2.4 (c, h). Federal Register, Vol. 59, No. 110, 9 June 1994.5.6.7.8.TP = True positivesTN = True negativesFP = False positivesFN = False negatives100 ng/mL n=93AxSYM PosAxSYM NegTDx NegGC/MS Pos09300CONCORDANCEAxSYM vs. TDx = 100%AxSYM vs. GC/MS = 100%TDx PosTDx NegGC/MS Pos8018111112CONCORDANCEAxSYM vs. TDx = 98%AxSYM vs. GC/MS = 87%TDx PosTDx NegGC/MS Pos6016113132CONCORDANCEAxSYM vs. TDx = 98%AxSYM vs. GC/MS = 66%TDx PosTDx NegGC/MS Pos2923116162CONCORDANCEAxSYM vs. TDx = 97%AxSYM vs. GC/MS = 33%TDx Pos930GC/MS Neg009.10.National Committee for Clinical Laboratory Standards. Urine Drug Testing in the Clinical Laboratory; Proposed Guideline. NCCLS Document T/DM8-P. Villanova, PA: NCCLS, 1993.11.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: 81-123.12.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, 1992.13.Fieser LF, Fieser M. Reagents for Organic Synthesis. New York: DJohn Wiley & Sons, Inc., 1967-84: Vols. 1-11.AxSYM, XSYSTEMS, REA, and Tx are trademarks of Abbott Laboratories.200 ng/mL n=93AxSYM PosAxSYM NegGC/MS Neg00400 ng/mL n=93AxSYM PosAxSYM NegGC/MS Neg00800 ng/mL n=93AxSYM PosAxSYM NegGC/MS Neg00AxSYM “Positive” = Concentration greater than or equal to the cut-off, 100, 200, 400 or 800 ng/mL of nordiazepam.TDx “Positive” = Concentration greater than or equal to the cut-off, 100, 200, 400 or 800 ng/mL of nordiazepam.DABBOTTMax-Planck-Ring 265205 WiesbadenGermany+49-6122-580Manufactured forAbbott Laboratories, Abbott Park ILbyAbbott Diagnostics International, LTD. Barceloneta, Puerto RicoAugust, 2008©1995, 2008 Abbott LaboratoriesGC/MS “Positive” = Concentration greater than or equal to 100 ng/mL of benzodiazepines and metabolites: Alprazolam, Bromazepam, Chlordiazepoxide, Clonazepam, Clorazepate, Diazepam, Flunitrazepam, Flurazepam, Lorazepam, Oxazepam, Prazepam, Temazepam or Triazolam.BIBLIOGRAPHY1.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.Schutz H. Benzodiazepines. A handbook. New York: Springer-Verlag, 1982;1-16.Kaplan SA, Jack ML. Metabolism of the benzodiazepines: Pharmacokinetic and pharmacodynamic considerations. In: Costa E, ed. The benzodiazepines from molecular biology to clinical practice. New York: Raven Press, 1983; 173-99.2.3.7
