E 3B40 34-3627/R5 Procainamide

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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.

Note Changes Highlighted

Key to symbols used

List Number Lot Number

For In Vitro Diagnostic Use Expiration Date

Standard Calibrator (A-F) Store at 2-8°C ©1996, 2005 Abbott Laboratories

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

Store at 15-30°C

Reagent Pack

CAUTION: Handle human sourced materials as potentially infectious. Consult instructions for use. (Infection Risk) Reaction Vessels

Sample Cups Consult instructions for use

Authorized Representative

Legal Manufacturer

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

ABBOTT Max-Planck-Ring 2 65205 Wiesbaden Germany +49-6122-580

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

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3B40-1C-20_Eng_ReIn.p65 1 6/3/2005, 12:49 PM Size: 8 1/2” x 11” Specific Plates: PMS 222 CVC PMS 3165 CVC Black

EDITOR: Mary DTP: Joe NAME REAGENTS Procainamide REAGENT PACK, 100 TESTS INTENDED USE AxSYM Procainamide Reagent Pack (3B40-20)* The AxSYM Procainamide assay is a reagent system for the • 1 Bottle (14.5 mL) < 25% Procainamide Antiserum (Rabbit, quantitative measurement of procainamide in serum or plasma. The Polyclonal) in phosphate buffer with protein stabilizers. measurements obtained are used in monitoring levels of Preservative: Sodium Azide. (Reagent Bottle 1) procainamide to ensure appropriate therapy. • 1 Bottle (8.6 mL) Pretreatment Solution. Surfactant in TRIS buffer. SUMMARY AND EXPLANATION OF TEST Preservative: Sodium Azide. (Reagent Bottle 2) The AxSYM Procainamide assay utilizes Fluorescence Polarization • 1 Bottle (15.1 mL) < 0.01% Procainamide Fluorescein Tracer in Immunoassay (FPIA) technology.1,2 Refer to the AxSYM System TRIS buffer. Preservative: Sodium Azide. (Reagent Bottle 3) Operations Manual, Section 3, under Principles of Operation for a *3B40-99 includes an AxSYM Procainamide Reagent Pack discussion of this technology. (100 Tests) and Reaction Vessels (100 each). 3B40-20 includes Procainamide is an effective and widely used antiarrhythmic drug. these items for international shipments. It has a narrow therapeutic index and can produce serious toxic CALIBRATORS side effects.3-6 The relationship between the dosage and the resulting AxSYM Procainamide Standard Calibrators (3B40-01) plasma concentration of procainamide has been found to be quite 6 Bottles (5 mL A, 4 mL each B-F) of AxSYM Procainamide variable among patients. This variability is due to several factors: Standard Calibrators. Calibrator A contains human serum, 1) differences in among individuals (individual nonreactive for HBsAg, HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2, phamacokinetics); 2) changes in the condition of the individual and Calibrators B-F contain accurately measured amounts of patient during therapy that alter drug metabolism; 3) pathologic procainamide prepared in human serum, nonreactive for HBsAg, conditions, such as renal impairment or cardiac failure, that have a HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2, to yield the following profound effect on drug disposition.3-6 Therefore, monitoring the concentrations: procainamide level in patient serum or plasma is recommended for safe and effective therapy. Procainamide Concentration The major metabolite of procainamide, N-acetylprocainamide Bottle (µg/mL & mg/L) (µmol/L) (NAPA, Acecainide), is also pharmacologically active. The amount of NAPA present depends on acetylator phenotype and metabolite 0.0 0.00 .5-7 Generally, its concentration is comparable to or greater 1.0 4.23 than that of procainamide.7 It has been suggested that the 2.5 10.58 concentrations of procainamide and N-acetylprocainamide should 5.0 21.15 be monitored simultaneously in order to optimize therapy.6,7 10.0 42.30 20.0 84.60 BIOLOGICAL PRINCIPLES OF THE PROCEDURE Preservative: Sodium Azide. The AxSYM Procainamide assay is based on Fluorescence Polarization Immunoassay (FPIA) technology. The AxSYM Abbott manufactures internal reference standards using Procainamide Reagents and sample are pipetted in the following Procainamide (USP Reference Standard). Procainamide calibrators sequence: are manufactured gravimetrically and tested against these internal reference standards. SAMPLING CENTER CONTROLS • Sample and all AxSYM Procainamide Reagents required for one test are pipetted by the sampling probe into various positions of AxSYM Procainamide Controls (3B40-10) a Reaction Vessel (RV). 3 Bottles (8 mL each) of AxSYM Procainamide Controls contain • Sample and Solution 4 (Line Diluent) are pipetted into one well procainamide prepared in human serum, nonreactive for HBsAg, of the RV (predilution mixture). HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2, to yield the following concentration ranges: • The pretreatment solution and Solution 4 (Line Diluent) are transferred to the cuvette of the RV. Procainamide The RV is immediately transferred into the Processing Center. Concentration Range Bottle (µg/mL & mg/L) (µmol/L) (µg/mL & mg/L) (µmol/L) Further pipetting is done in the Processing Center with the processing probe. 2.0 8.46 1.60 - 2.40 6.77 - 10.15 7.0 29.61 5.90 - 8.10 24.96 - 34.26 PROCESSING CENTER 15.0 63.45 12.30 - 17.70 52.03 - 74.87 • An aliquot of the predilution mixture and Solution 4 (Line Diluent) Preservative: Sodium Azide. are transferred to the cuvette of the RV and the blank intensity The default result unit for AxSYM Procainamide is µg/mL. An of the sample is measured. alternate unit (mg/L or µmol/L) can be selected for reporting results • A second aliquot of the predilution mixture is transferred to the (Assay Parameter 45). cuvette along with the Procainamide Antiserum (antibody) and OTHER REAGENTS the Procainamide Fluorescein Tracer. AxSYM Probe Cleaning Solution (9A35-05) • Procainamide from the sample and the Procainamide Fluorescein Tracer compete for binding sites on the antibody 2 Bottles (220 mL each) AxSYM Probe molecule. Cleaning Solution containing 2% Tetraethylammoniumhydroxide • The intensity of polarized fluorescent light is measured by the (TEAH). FPIA optical assembly. Solution 4 (Line Diluent) (8A46) For further information, refer to the AxSYM System Operations 1 Bottle (10 L) Solution 4 (Line Diluent) Manual, Section 3. containing 0.1M Phosphate Buffer. Preservatives: Sodium Azide and Antimicrobial Agent. 2

3B40-1C-20_Eng_ReIn.p65 2 6/3/2005, 12:49 PM WARNINGS AND PRECAUTIONS Reagents are stable until the expiration date when stored and For In Vitro Diagnostic use. handled as directed. SAFETY PRECAUTIONS The AxSYM Probe Cleaning Solution and Solution 4 • CAUTION: This product contains human sourced and/or (Line Diluent) must be stored at 15-30°C. potentially infectious components. For a specific listing, refer to INSTRUMENT PROCEDURE the REAGENTS section of this package insert. Components Assay File Installation sourced from human blood have been tested and found to be nonreactive for HBsAg, HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2 The AxSYM Procainamide Assay File must be installed on the by FDA licensed tests. No known test method can offer complete AxSYM System from one of the following software disks, prior to assurance that products derived from human sources or performing the Procainamide assay: inactivated microorganisms will not transmit infection. Therefore, • 2C47-01, or higher (112 hours on-board Stability) all human sourced materials should be considered potentially • 3D53-01, or higher (224 hours on-board Stability) infectious. It is recommended that these reagents and human Refer to the AxSYM System Operations Manual, Section 2, for proper specimens be handled in accordance with the OSHA Standard installation procedures. on Bloodborne Pathogens.8 Biosafety Level 29 or other AxSYM Procainamide Assay Parameters appropriate biosafety practices10,11 should be used for materials that contain or are suspected of containing infectious agents. The default values for the assay parameters used for the AxSYM Procainamide assay are listed below. Assay parameters that can • The AxSYM Probe Cleaning Solution (2% TEAH) may cause be edited contain a (>) symbol. These parameters can be displayed mild eye irritation. If this solution comes in contact with eyes, and edited according to the procedure in the AxSYM System rinse immediately with water. If irritation persists, seek medical Operations Manual, Section 2. In order to obtain values for the attention. parameters with an asterisk (*), review the specific Assay Parameter • Some components of this product contain Sodium Azide. For a screen. Press PRINT to print the assay parameters. specific listing, refer to the REAGENTS section of this package insert. The components containing Sodium Azide are classified Assay Parameters per applicable European Community (EC) Directives as: Harmful 1 Long Assay Name (English): Procainamide (Xn). The following are the appropriate Risk (R) and Safety (S) 6 Abbrev Assay Name (English): Procain phrases. 11 Assay Number: 650 R22 Harmful if swallowed. 12 Assay Version: * R32 Contact with acids liberates very toxic gas. 13 Calibration Version: * S35 This material and its container must be disposed of in 14 Assay File Revision: * a safe way. 15 Assay Enabled > ON S36 Wear suitable protective clothing. S46 If swallowed, seek medical advice immediately and 17 Assay Type: FPIA show this container or label. 18 Standard Cal Reps > 2 • Information for European customers: For product not classified 21 Cal A Concentration: 0.00 as dangerous per European Directive 1999/45/EC - Safety data 22 Cal B Concentration: 1.00 sheet available for professional user on request. 23 Cal C Concentration: 2.50 HANDLING PRECAUTIONS 24 Cal D Concentration: 5.00 25 Cal E Concentration: 10.00 • Do not use kits beyond the expiration date or a maximum of 224 26 Cal F Concentration: 20.00 cumulative hours on-board the AxSYM System. 43 Default Dilution Protocol > UNDILUTED • Do not mix reagents from different reagent packs. 44 Default Calibration Method > Standard Calibration Refer to the AxSYM System Operations Manual, Sections 7 and 8, 45 Selected Result Concentration Units > ug/mL for a more detailed discussion of the safety and handling precautions 46 Selected Result Decimal Places > 2 during system operation. 62 Blank I-Max background intensity: * STORAGE INSTRUCTIONS 63 Min Tracer-Min net intensity: * 73 Low Limit-Normal/Therapeutic Range lower limit > 0.00 74 Hi Limit-Normal/Therapeutic Range upper limit > 0.00 The AxSYM Procainamide Reagent Pack, Calibrators and 75 Low Extreme Value > 0.38 Controls must be stored at 2-8°C. The AxSYM Procainamide 76 High Extreme Value > 200.00 Reagent Pack, Calibrators and Controls may be used immediately 91 Low Range Neat: * after removing them from the refrigerator. Calibrators and Controls 92 High Range Neat: * should be returned to 2-8°C storage immediately after use. Do not 96 Low Range Dil1: * freeze AxSYM Procainamide Reagents. 97 High Range Dil1: * The AxSYM Procainamide Reagent Pack may be on-board the Note: Parameter #45 can be edited to the alternate result unit µmol/L AxSYM System for a maximum of 224 cumulative hours; for example, or mg/L. 28 eight hour shifts. Recalibration may be required to obtain Values associated with the Low and High Extreme flags, Assay maximum on-board reagent stability. More frequent use of controls Parameter #75 and 76, are assay specific and should not be edited. may be required to monitor reagent performance within the same lot. We recommend that you set General Configuration Parameter, Release Mode, to the “Manual”or “Hold” release mode to ensure Refer to the AxSYM System Operations Manual, Sections 2, 5 and that all flagged results are reviewed prior to reporting assay results. Appendices, for further information on tracking on-board time.

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3B40-1C-20_Eng_ReIn.p65 3 6/3/2005, 12:49 PM Refer to the AxSYM System Operations Manual, Section 2, for a AxSYM PROCAINAMIDE PROCEDURE detailed description of Instrument Procedures. If General Materials Provided Configuration Parameter, Release Mode, is configured to the • 3B40-99 AxSYM Procainamide Reagent Kit, containing: “Automatic” Release Mode, ensure that all flagged results are AxSYM Procainamide reviewed prior to reporting assay results. 100 SAMPLE COLLECTION AND PREPARATION FOR Materials Required But Not Provided ANALYSIS • 3B40-01 AxSYM Procainamide Standard Calibrators • Serum or plasma (collected in sodium heparin, citrate, EDTA, or • 3B40-10 AxSYM Procainamide Controls oxalate collection tubes) may be used in the AxSYM • 8A46 Procainamide assay. Follow the manufacturer’s processing instructions for serum or plasma collection tubes. • 9A35-05 AxSYM • The AxSYM System does not provide the capability of verifying • 8A76-01 the sample type. It is the responsibility of the operator to verify • Pipettor and pipette tips (optional) to deliver the volumes specified the sample type(s) used in the Procainamide assay. on the Order screen. • Ensure that complete clot formation has taken place prior to CAUTION: centrifugation. Some samples, especially those from patients • For optimal performance it is important to follow the routine receiving anticoagulant or thrombolytic therapy, may exhibit maintenance procedures defined in the AxSYM System increased clotting time. If the sample is centrifuged before a Operations Manual, Section 9. If your laboratory requires more complete clot forms, the presence of fibrin may cause erroneous frequent maintenance, follow those procedures. results. Assay Procedure • Specimens containing particulate matter or red blood cells may Sections 5 and 6 of the AxSYM System Operations Manual, can be give inconsistent results and should be centrifuged before testing easily removed for use at the instrument. They contain detailed steps (recommended 8,000-10,000 RCF* x 10 minutes). for performing assay calibration and sample testing procedures. • Samples may be stored for up to 24 hours at 2-8°C prior to being Prior to ordering tests, confirm that the system inventory of Reaction tested. If testing will be delayed more than 24 hours, the serum Vessels (RVs), bulk solutions and waste levels are acceptable. or plasma should be separated from the clot or red blood cells The operator may obtain an Orderlist Report by pressing PRINT. and stored frozen at -10°C or colder for up to 168 hours. The printout contains sample placement information and minimum • Refer to the AxSYM System Operations Manual, Section 5, for a STAT sample cup volume requirements for all tests ordered. When detailed discussion of on-board sample storage constraints. using Host Order Query the Orderlist Report is not available. Refer • Inspect all samples for bubbles. Remove bubbles prior to to the AxSYM System Operations Manual, Section 5: Ordering analysis. Patient Samples, for a description of the Host Order Query option. • When shipped, samples must be packaged and labeled in CAUTION: When operating the AxSYM System, always observe compliance with applicable federal and international regulations the following: covering the transport of clinical samples and etiologic agents. • The System status must be WARMING, PAUSED, READY or *Relative Centrifugal Force. STOPPED before adding or removing sample segments, reagent SAMPLE VOLUME packs or Reaction Vessels (RVs). The sample volume required to perform a single undiluted • When only performing FPIA assays, the instrument homes all Procainamide test on the AxSYM System varies depending on the motors and may display “Error Code 5066 Matrix cell not type of sample container used. For sample cups, a ROUTINE test detected, trap door, processing center”. Select OK to proceed requires 150 µL and a STAT test requires 89 µL. For every additional with testing the FPIA assays. Procainamide test performed (ROUTINE or STAT) from the same • Do not open the Interior Waste Door or the AxSYM Processing sample container, an additional 39 µL of sample is required. Center Cover while any test is in process. If opened, all The sample cup minimum volumes for both ROUTINE and STAT processing will stop. Tests in process will be terminated and must tests (undiluted or diluted) are calculated by the AxSYM System. be repeated. They are displayed on the Order screen at the time the test(s) is(are) • When testing is completed, it is recommended that samples and ordered. When using Host Order Query, the Order screen information the AxSYM Procainamide Reagent Pack are removed from the and Orderlist Report are not available. Refer to the AxSYM System Sampling Center to maximize the on-board reagent pack use. Operations Manual, Section 5: Ordering Patient Sample, for a Store Reagent Pack at 2-8°C. description of the Host Order Query option. QUALITY CONTROL PROCEDURES If the assay is configured for auto retest/auto dilution, the additional CALIBRATION 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 The AxSYM Procainamide assay must be calibrated using a total sample volume should include an additional 39 µL of sample. Standard Calibration (6-point) procedure. For sample volume requirements in primary or aliquot tubes, and Standard Calibration calibrator and control requirements for multiple reagent lots, refer to To perform a Standard Calibration, test the AxSYM Procainamide the AxSYM System Operations Manual, Section 5. Standard Calibrators A, B, C, D, E, and F in duplicate. A single sample To obtain the recommended volume requirements for the AxSYM of all levels of Procainamide controls must be tested as a means of Procainamide Calibrators and Controls, hold the bottles vertically evaluating the assay calibration. and dispense 4 drops of each calibrator or control into each respective sample cup.

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3B40-1C-20_Eng_ReIn.p65 4 6/3/2005, 12:49 PM Once the AxSYM Procainamide calibration is accepted and stored, Alternate Result Units all subsequent samples may be tested without further calibration The default result unit for AxSYM Procainamide is µg/mL. When unless: selecting the alternate result unit, µmol/L, the conversion factor used • A reagent pack with a new lot number is used by the AxSYM System is 4.23. When selecting the alternate result • Control values are out of their specified range unit, mg/L, the conversion factor used by the AxSYM System is 1.00. Refer to the AxSYM System Operations Manual, Section 6, for: Flags • Setting up an assay calibration Some results may contain information in the Flags field. Samples • When recalibration may be necessary flagged as low extreme values (LL), Assay Parameter #75, must be reviewed prior to reporting assay results. Results at or near • Calibration Verification the assay sensitivity should be verified prior to reporting drug The AxSYM System verifies that the results of an assay calibration concentrations. For a description of the other flags that may appear meet the specifications assigned to selected validity parameters. in this field, refer to the AxSYM System Operations Manual, An error message occurs when the calibration fails to meet a Section 1. specification. Refer to the AxSYM System Operations Manual, Section 10, for an explanation of the corrective actions for the error LIMITATIONS OF THE PROCEDURE code. Refer to the AxSYM System Operations Manual, Appendices, As with all analyte determinations, the procainamide value should for an explanation of the calibration validity parameters that may be be used in conjunction with information available from clinical used by the AxSYM System. evaluation and other diagnostic procedures. Operator Verification SAMPLE DILUTION PROCEDURES An acceptable Procainamide calibration curve should meet the Automated Dilution Protocol following criteria: Patient samples with procainamide concentrations reported as a) Polarization Error (PERR) -3.50 to +3.50 for all calibrators. greater than 20.00 µg/mL may be diluted using an automated dilution b) Root Mean Squared Error (RMSE) less than or equal to 2.00. protocol. The AxSYM System automatically calculates the concentration of the diluted sample and reports the result. Refer to c) All control levels are within the acceptable ranges. the AxSYM System Operations Manual, Section 5, for additional NOTE: PERR’s and RMSE’s are to be used as guidelines only. If information on ordering sample dilutions. controls are within specified ranges, the calibration curve is Manual Dilution Protocol acceptable. Patient samples with procainamide concentrations reported as QUALITY CONTROL greater than 40.00 µg/mL by the Automated Dilution Protocol may The recommended control requirement for the AxSYM Procainamide be diluted using a manual dilution of 1:10. Add one part of the patient assay is a single sample of at least two different Procainamide control sample to nine parts of the AxSYM Procainamide Calibrator A. levels, which span the medical decision range, tested once every Repeat the test using this manually diluted sample. The concentration 24 hours, each day of use. Controls may be placed in any position reported by the AxSYM System must be multiplied by the manual in the Sample Carousel. dilution factor to obtain the final sample concentration. If the quality control procedures in your laboratory require more Final Sample frequent use of controls to verify test results, follow those procedures. = Reported Concentration x Manual Dilution Factor Concentration To achieve maximum on-board reagent stability, more frequent use

of controls may be required to monitor reagent performance within Manual = (Volume of Sample + Volume of Dilution Reagent) the same lot. Dilution Factor Volume of Sample Ensure that assay control values are within the concentration ranges EXPECTED VALUES specified in the package insert. Refer to the REAGENTS, Extensive studies have shown that the therapeutic and toxic effects CONTROLS section of this package insert for AxSYM Procainamide of procainamide are closely related to serum or plasma Control ranges. concentration.3-6 The commonly accepted therapeutic range for INDICATIONS OF INSTABILITY OR DETERIORATION OF procainamide is 4-10 µg/mL. It is thought to be toxic at levels greater REAGENTS than 16 µg/mL. The presence of the active metabolite, When a control value is out of the specified range, it may indicate N-acetylprocainamide, creates problems in the interpretation of deterioration of the reagents or errors in technique. Associated test therapeutic drug monitoring information. It has been suggested that results may be invalid and require retesting. Assay recalibration may a total serum concentration of 5 µg/mL for procainamide plus NAPA be indicated. Refer to the AxSYM System Operations Manual, is a reasonable lower limit for the therapeutic range and total serum Section 10, Subsection: Observed Problems, for further concentration of 20-30 µg/mL is a reasonable upper limit.7 Further troubleshooting information. studies are required to more accurately determine the relationship The AxSYM System has a capability to generate a Levey-Jennings of the combined procainamide and N-acetylprocainamide plot of each assay’s quality control performance. Refer to the AxSYM concentrations to therapeutic effect. System Operations Manual, Section 5, for further information. At Refer to the drug manufacturer’s package insert or the Physicians’ the discretion of the laboratory, selected quality control rules may Desk Reference® (PDR) for proper drug dosage and for be applied to the quality control data. procainamide measurement sampling times. RESULTS The AxSYM Procainamide assay utilizes a four parameter logistic curve fit method (4PLC, Y weighted) to generate a calibration curve. This curve is stored in memory and concentrations of drug in controls and unknown samples are calculated from this curve using polarization values generated.

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3B40-1C-20_Eng_ReIn.p65 5 6/3/2005, 12:49 PM SPECIFIC PERFORMANCE CHARACTERISTICS Test Compound Tested Concentration % Cross-reactivity PRECISION (µg/mL) Precision was determined as described in National Committee for N-acetylprocainamide 10 ND Clinical Laboratory Standards (NCCLS) protocol EP5-T212 using 100 0.3 human serum with 2.0, 7.0, and 15.0 µg/mL of procainamide added. Deethylprocainamide 1 ND Results from these studies typically yielded CV’s of less than 6%. 10 8.0 Deethyl-N-acetylprocainamide 1 ND The following are representative results from pooled data from one 10 ND reagent lot tested on four instruments for a total of four precision studies. ND = none detected; concentration less than assay sensitivity (0.25 µg/mL). The following compounds showed less than 0.1% cross-reactivity Concentration (µg/mL) when tested with the Procainamide assay: furosemide (tested at Target value 2.0 7.0 15.0 5000 µg/mL); p-acetamidobenzoic acid, p-aminobenzoic acid, (n=80) acetaminophen, clonidine, disopyramide, ephedrine, guanethidine, Mean 2.00 6.83 14.55 hydralazine, hydrochlorothiazide, lidocaine, methamphetamine, SD Within Run 0.08 0.24 0.62 monoethylglycinexylidide (MEGX), ouabain, phenytoin, propranolol, CV Within Run (%) 4.00 3.51 4.26 SD Between Day 0.03 0.08 0.22 quinidine, reserpine, salicylate, tocainide and triamterene (tested at CV Between Day (%) 1.50 1.17 1.51 1000 µg/mL); clonazepam and isoproterenol (tested at 100 µg/mL); SD Total 0.10 0.28 0.70 digitoxin and digoxin (tested at 1 µg/mL). CV Total (%) 5.00 4.10 4.81 INTERFERENCE ACCURACY BY RECOVERY The compounds listed below, added to human serum, resulted in Recovery was determined by adding procainamide to human serum less than 10% error in detecting added drug when assayed with the and to buffer at concentrations of 1.0, 2.5, 5.0 and 10.0 µg/mL. The AxSYM Procainamide assay. concentration of procainamide was determined using the AxSYM Compound Concentration Tested Procainamide assay, and the resulting % recovery was calculated • Bilirubin 20 mg/dL according to the following equation: • Hemoglobin 1.0 g/dL % Recovery = (“serum concentration” divided by “buffer concentration”) x 100 • Triglycerides 1000 mg/dL Representative data are shown in the following table. • Total Protein 3.5-10.0 g/dL Added Concentration Concentration Percent (%) ACCURACY BY CORRELATION Concentration in serum in Buffer Recovery (µg/mL) (µg/mL) (µg/mL) The Abbott AxSYM Procainamide assay was compared to a commercially available Fluorescence Polarization Immunoassay. 1.0 0.91 0.94 96.8 The results of the specimen testing are shown in the following table. 2.5 2.54 2.45 103.7 5.0 5.06 4.86 104.1 Number of Correlation 10.0 9.20 9.30 98.9 Manufacturer Observations Intercept Slope Coefficient Average Recovery: 100.9 + 5.0% Abbott AxSYM SENSITIVITY Procainamide vs. 206 0.1 0.98 0.99 The sensitivity of the AxSYM Procainamide assay was calculated Abbott TDx®/TDxFLx® to be 0.25 µg/mL. This sensitivity is defined as the lowest measurable Procainamide* concentration that can be distinguished from zero with 95% confidence. * Sample Range (AxSYM Procainamide): 0.52 - 17.32 µg/mL SPECIFICITY BIBLIOGRAPHY Cross-reactivity was tested for compounds whose chemical structure 1. Jolley ME. Fluorescence polarization immunoassay for or concurrent usage could cause potential interference with the determination of therapeutic drug levels in human plasma. J Anal AxSYM Procainamide assay. Procainamide samples Tox 1981; 5:236–40. (5 and 10 µg/mL) containing the metabolites, N-acetylprocainamide 2. Jolley ME, Stroupe SD, Schwenzer KS, et al. Fluorescence (15 µg/mL), deethylprocainamide (1 µg/mL) or deethyl-N- polarization immunoassay III. An automated system for acetylprocainamide (1 µg/mL) showed no apparent change in therapeutic drug determination. Clin Chem 1981; 27:1575–9. procainamide concentration (less than 0.4 µg/mL incremental 3. Koch-Weser J, Klein SW. Procainamide dosage schedules, change). Additionally, cross-reactivity of procainamide metabolites plasma concentrations and clinical effects. JAMA 1971; and other commonly administered drugs was also established by 215:1454–60. spiking procainamide-free pooled human serum with the test 4. Garfein OB. of commonly used antiarrhythmic compounds and then assaying the sample by the AxSYM drugs and comments on the use of therapeutic drug monitoring. Procainamide assay. The results of the cross-reactivity studies are Ther Drug Monit 1982; 4:1–14. shown in the following table. 5. Brown JE, Shand DG. Therapeutic drug monitoring of antiarrhythmic agents. Clin Pharmacokinet 1982; 7:125–48. 6. Karlsson E. Clinical of procainamide. Clin Pharmacokinet 1978; 3:97–107.

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3B40-1C-20_Eng_ReIn.p65 6 6/3/2005, 12:49 PM 7. Atkinson AJ Jr, Strong JM. Effect of active drug metabolites on plasma level-response correlations. J Pharmacokinet Biopharm 1977; 5:95–109. 8. US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 1910.1030, Occupational Exposure to Bloodborne Pathogens. 9. US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories, Fourth Edition. Washington, DC: US Government Printing Office, May 1999. 10. World Health Organization. Laboratory Biosafety Manual. Geneva: World Health Organization; 2004. 11. 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. 12. National Committee for Clinical Laboratory Standards. Evaluation of precision performance of clinical chemistry devices-Second Edition; Tentative Guideline. NCCLS document EP5-T2 (ISBN 1-56238-145-8). NCCLS, 771 East Lancaster Avenue, Villanova, Pennsylvania 19085, 1992. Related Reading Physicians’ Desk Reference®. 49th Edition. Montvale, NJ: Medical Economics Co. Inc., 1995. Ruo TI, Morita Y, Atkinson AJ Jr, Henthorn T, Thenot JP. Identification of desethylprocainamide in patients: A new metabolite of procainamide. J Pharmacol Exp Ther 1981; 216:357–62. Ruo TI, Thenot JP, Stec GP, Atkinson AJ Jr. Plasma concentration of desethyl N-acetylprocainamide in patients treated with procainamide and N-acetylprocainamide. Ther Drug Monit 1981; 3:231–7. AxSYM, TDx and TDxFLx are registered trademarks of Abbott Laboratories, Abbott Park, IL 60064 USA

Abbott Laboratories Diagnostics Division Abbott Park, IL 60064 USA June, 2005

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