(29 days)
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-to-use liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
The assay consists of reagents (A and E).
Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.
Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at cutoff concentrations of either 150 ng/mL or 300 ng/mL. The study performed aims to demonstrate the analytical performance of the device and its substantial equivalence to the predicate device, Cocaine Metabolite Enzyme Immunoassay (K960187).
Here's an analysis of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for agreement percentages (e.g., "must be >95%"). However, the reported performance demonstrates 100% agreement with the reference method (LC-MS/MS) for both positive and negative samples at both cutoff levels in the method comparison study. The precision studies also show consistent determination of positive and negative results at concentrations significantly above and below the cutoff, with expected mixed results at the cutoff itself.
| Study Component | Acceptance Criteria (Implicit/Inferred) | Reported Device Performance (150 ng/mL Cutoff) | Reported Device Performance (300 ng/mL Cutoff) |
|---|---|---|---|
| Precision (Qualitative) | Consistent results at concentrations +/- cutoff, mixed at cutoff | At cutoff: 22/58 (N/P), <25% below: all negative, >25% above: all positive | At cutoff: 31/49 (N/P), <25% below: all negative, >25% above: all positive |
| Precision (Semi-Quantitative) | Consistent results at concentrations +/- cutoff, mixed at cutoff | At cutoff: 19/61 (N/P), <25% below: all negative, >25% above: all positive | At cutoff: 22/58 (N/P), <25% below: all negative, >25% above: all positive |
| Spike Recovery (Qualitative) | No overlap between results below and above cutoff | All 21 replicates below cutoff were Negative; All 21 replicates above cutoff were Positive | All 21 replicates below cutoff were Negative; All 21 replicates above cutoff were Positive |
| Analytical Recovery & Linearity | Percent recovery close to 100% | Range: 95.9% to 108.9% (excluding 0 ng/mL) | Consistent with 150 ng/mL, not explicitly stated separately |
| Method Comparison (Semi-Qualitative) - Agreement among Positives | High agreement with reference method | 100% (50/50) | 100% (50/50) |
| Method Comparison (Semi-Qualitative) - Agreement among Negatives | High agreement with reference method | 100% (50/50) | 100% (50/50) |
| Method Comparison (Qualitative) - Agreement among Positives | High agreement with reference method | 100% (50/50) | 100% (50/50) |
| Method Comparison (Qualitative) - Agreement among Negatives | High agreement with reference method | 100% (50/50) | 100% (50/50) |
| Specificity (Cocaine metabolites) | Cross-reactivity % values acceptable | Benzoylecgonine: 100%, Cocaine: 0.6%, Cocaethylene: 0.5%, Ecgonine: 0.17%, Ecgonine Methyl Ester: <0.15%, m-hydroxybenzoylecgonine: 50%, Norcocaine: <0.15% | Benzoylecgonine: 100%, Cocaine: 0.6%, Cocaethylene: 0.5%, Ecgonine: 0.19%, Ecgonine Methyl Ester: <0.3%, m-hydroxybenzoylecgonine: 50%, Norcocaine: <0.3% |
| Specificity (Unrelated compounds) | No interference at tested concentrations | Low control: Negative, High control: Positive for all tested compounds | Low control: Negative, High control: Positive for all tested compounds |
| Interference (Physiologic substances & pH) | No interference at tested concentrations | Low control: Negative, High control: Positive for all tested compounds | Low control: Negative, High control: Positive for all tested compounds |
| Specific Gravity Interference | No interference across range | Low control: Negative, High control: Positive for all tested ranges | Low control: Negative, High control: Positive for all tested ranges |
2. Sample Size for the Test Set and Data Provenance
- Precision Studies:
- For both qualitative and semi-quantitative modes and both cutoffs (150 ng/mL and 300 ng/mL): 80 replicates (2 replicates per day for 20 days).
- Includes samples with Benzoylecgonine spiked at cutoff, 25%, 50%, 75%, and 100% above and below the cutoff.
- Spike Recovery: 21 replicates for each spiked concentration (112.5 ng/mL and 187.5 ng/mL for 150 ng/mL cutoff; 225 ng/mL and 375 ng/mL for 300 ng/mL cutoff).
- Analytical Recovery and Linearity: 9 intermediate levels (plus 0 and 1025 ng/mL), each run in replicates of five.
- Method Comparison and Accuracy:
- 100 patient samples were analyzed.
- Specificity (Cocaine metabolites): Not specified by number of samples, but by "known amounts of each compound."
- Specificity (Structurally Unrelated Compounds): Not specified by number of samples, but by spiking into low and high control urine.
- Interference (Physiologic Substances & pH): Not specified by number of samples, but by spiking into low and high control urine.
- Specific Gravity Interference: Not specified by number of samples, but by spiking drug-free urine with varying specific gravities.
Data Provenance: The studies were performed at the manufacturer's site (Microgenics Corporation, Thermo Fisher Scientific). The data appears to be retrospective (spiked samples, patient samples compared to LC-MS/MS). The country of origin of the data is not explicitly stated, but the manufacturer is based in Fremont, California, USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This being an in vitro diagnostic (IVD) device for drug toxicology, the ground truth is established by a reference analytical method rather than human expert interpretation of images or clinical findings.
- No human experts were used to establish ground truth for the test set.
- The primary reference method for accuracy studies was LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry), which is considered the preferred confirmatory method for drug testing due to its high specificity and sensitivity.
4. Adjudication Method
As ground truth was established by an objective analytical method (LC-MS/MS) and not human reader consensus, no adjudication method (e.g., 2+1, 3+1) was applicable or used.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No MRMC study was conducted or is applicable for this type of IVD device. This device is an immunoassay for determining drug metabolites, not an AI-powered diagnostic imaging tool that assists human readers. Therefore, the concept of human reader improvement with AI assistance is not relevant here.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire document describes the performance of the algorithm/device only (DRI Cocaine Metabolite Assay) without human-in-the-loop performance, against established analytical standards and a reference method (LC-MS/MS). The device generates a preliminary analytical test result independently.
7. Type of Ground Truth Used
The ground truth used for performance evaluation, particularly for accuracy and method comparison, was Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS). This is a highly accurate chemical method considered the gold standard for confirming drug presence and concentration. For precision, spike recovery, and interference studies, the ground truth involved precisely spiking known concentrations of the analyte into drug-free urine.
8. Sample Size for the Training Set
The document describes the analytical performance of a finished device. It does not mention any "training set" in the context of machine learning. This device is a biochemical immunoassay, not a machine learning model that requires a training set.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, there is no disclosed "training set" or machine learning component in the context of this immunoassay. Therefore, this question is not applicable.
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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.
July 6, 2018
Microgenics Corporation Emily Chien Regulatory Affairs Specialist II 46500 Kato Road Fremont, California 94538
Re: K181499
Trade/Device Name: DRI Cocaine Metabolite Assay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Code: DIO Dated: June 5. 2018 Received: June 7, 2018
Dear Emily Chien:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula Caposino -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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| DEPARTMENT OF HEALTH AND HUMAN SERVICES | |
|---|---|
| Food and Drug Administration | |
| Indications for Use | |
| Form Approved: OMB No. 0910-0120 | |
| Expiration Date: 06/30/2020 | |
| See PRA Statement below. | |
| 510(k) Number ( if known ) | K181499 |
| Device Name | DRI Cocaine Metabolite Assay |
| Indications for Use (Describe) | The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. |
| The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures. | |
| The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications. | |
| Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only. | |
| Type of Use (Select one or both, as applicable) | |
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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5. 510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
A. Device Information
| Category | Comments |
|---|---|
| Sponsor: | Microgenics CorporationThermo Fisher Scientific46500 Kato RoadFremont, CA 94538Phone: 510-979-5000FAX: 510-979-5002 |
| Correspondent ContactInformation: | Emily ChienRegulatory Affairs Specialist IIEmail: Emily.Chien@thermofisher.comPhone: 510-979-5000FAX: 510-979-5002 |
| Device Common Name: | Cocaine Metabolite Enzyme Immunoassay |
| Trade or Proprietary Name | DRI Cocaine Metabolite Assay |
| Candidate Device ProductCode, Classification,Classification Name &Panel | DIO, Class II, 21 CFR 862. 3250 - Cocaine MetaboliteTest System, 91 - Toxicology |
Predicate Device Information:
| Predicate Device: | Cocaine Metabolite Enzyme Immunoassay |
|---|---|
| Predicate DeviceManufacturer: | Diagnostic Reagents, Inc. |
| Predicate Device PremarketNotification #: | K960187 |
B. Date Summary Prepared July 06, 2018
July 06, 2018
C. Description of Device
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody
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binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
The assay consists of reagents (A and E).
Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.
Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.
D. Intended Use
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
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E. Comparison to Predicate Device
| Characteristics | Candidate Device:DRI CocaineMetabolite Assay | Predicate Device:Cocaine Metabolite EnzymeImmunoassay (K960187) |
|---|---|---|
| Intended Use | The DRI CocaineMetabolite Assay is ahomogeneous enzymeimmunoassay intended forthe qualitative and/or semi-quantitative determinationof benzoylecgonine(Cocaine Metabolite) inhuman urine at a cutoffconcentration of either 150ng/mL or 300 ng/mL. | This homogeneous cocainemetabolite enzymeimmunoassay is intended tobe used for qualitative andsemi-quantitativedetermination ofbenzoylecgonine (cocainemetabolite) in human urinewith either 300 ng/ml or 150ng/ml as a cutoff calibrator. |
| OperatingPrinciple(Technology) | DRI | Same |
| MeasuredAnalyte | Benzoylecgonine | Same |
| Test Matrix | Urine | Same |
| Cut-off Levels | 150 ng/mL and 300 ng/mL | Same |
| Methodology | Homogeneous EnzymeImmunoassay | Same |
| Reagents Form | Liquid ready-to-use. | Same |
| Antibody | Mouse monoclonalantibodies | Same |
| Storage | 2-8 °C until expiration date | Same |
| PrincipalOperator | Trained professionals | Same |
| Calibrator Levelsfor Semi-Quant | 5 point calibrator | 3 point calibrator |
F. Test Principle
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The DRI technology is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
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G. Summary of Supporting Data
1. Analytical Performance:
Performance is evaluated at the manufacturer's site on the Beckman Coulter AU680 clinical analyzer.
a) Precision
Precision studies were performed in accordance with CLSI Guideline EP05-A3. Samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine at the cutoff, 25%, 50%, 75% and 100% above and below the cutoff and tested in both qualitative and semi-quantitative modes. Results presented below were generated by testing all samples in replicates of 2, twice per day for 20 days, total n=80. The results for both cutoffs are summarized in the tables below.
| SpikedConcentration(ng/mL) | % of Cutoff(150 ng/mL) | Total Precision (n=80) | |
|---|---|---|---|
| # ofDeterminants | ImmunoassayResults(Negative/Positive) | ||
| 0 | -100% | 80 | 80/0 |
| 37.5 | -75% | 80 | 80/0 |
| 75 | -50% | 80 | 80/0 |
| 112.5 | -25% | 80 | 80/0 |
| 150 | 100% | 80 | 22/58 |
| 187.5 | +25% | 80 | 0/80 |
| 225 | +50% | 80 | 0/80 |
| 262.5 | +75% | 80 | 0/80 |
| 300 | +100% | 80 | 0/80 |
Qualitative Study Analysis for 150 ng/mL cutoff
Qualitative Study Analysis for 300 ng/mL cutoff
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| Spiked | % of Cutoff(300 ng/mL) | Total Precision (n=80) | |
|---|---|---|---|
| Concentration(ng/mL) | # ofDeterminants | ImmunoassayResults(Negative/Positive) | |
| 0 | -100% | 80 | 80/0 |
| 75 | -75% | 80 | 80/0 |
| 150 | -50% | 80 | 80/0 |
| 225 | -25% | 80 | 80/0 |
| 300 | 100% | 80 | 31/49 |
| 375 | +25% | 80 | 0/80 |
| 450 | +50% | 80 | 0/80 |
| 525 | +75% | 80 | 0/80 |
| 600 | +100% | 80 | 0/80 |
Semi-Quantitative Study Analysis for 150 ng/mL cutoff
| Spiked | % of Cutoff(150 ng/mL) | Total Precision (n=80) | |
|---|---|---|---|
| Concentration(ng/mL) | # ofDeterminants | ImmunoassayResults(Negative/Positive) | |
| 0 | -100% | 80 | 80/0 |
| 37.5 | -75% | 80 | 80/0 |
| 75 | -50% | 80 | 80/0 |
| 112.5 | -25% | 80 | 80/0 |
| 150 | 100% | 80 | 19/61 |
| 187.5 | +25% | 80 | 0/80 |
| 225 | +50% | 80 | 0/80 |
| 262.5 | +75% | 80 | 0/80 |
| 300 | +100% | 80 | 0/80 |
Semi-Quantitative Study Analysis for 300 ng/mL cutoff
| SpikedConcentration(ng/mL) | % of Cutoff(150 ng/mL) | Total Precision (n=80) | |
|---|---|---|---|
| # ofDeterminants | ImmunoassayResults(Negative/Positive) | ||
| 0 | -100% | 80 | 80/0 |
| 75 | -75% | 80 | 80/0 |
| 150 | -50% | 80 | 80/0 |
| 225 | -25% | 80 | 80/0 |
| 300 | 100% | 80 | 22/58 |
| 375 | +25% | 80 | 0/80 |
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| SpikedConcentration(ng/mL) | % of Cutoff(150 ng/mL) | Total Precision (n=80) | |
|---|---|---|---|
| # ofDeterminants | ImmunoassayResults(Negative/Positive) | ||
| 450 | +50% | 80 | 0/80 |
| 525 | +75% | 80 | 0/80 |
| 600 | +100% | 80 | 0/80 |
b) Spike Recovery
The study was performed for 21 replicates. This study was carried out by testing spiked samples containing Benzoylecgonine (Cocaine Metabolite) at the cutoff calibrator and control levels. The spiked samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine. Samples were tested in both qualitative and semi-quantitative mode. The qualitative results for both cutoffs are summarized in the tables below.
| Replicates | 112.5 ng/mL(n=21) | 187.5 ng/mL(n=21) |
|---|---|---|
| 1 | Negative | Positive |
| 2 | Negative | Positive |
| 3 | Negative | Positive |
| 4 | Negative | Positive |
| 5 | Negative | Positive |
| 6 | Negative | Positive |
| 7 | Negative | Positive |
| 8 | Negative | Positive |
| 9 | Negative | Positive |
| 10 | Negative | Positive |
| 11 | Negative | Positive |
| 12 | Negative | Positive |
| 13 | Negative | Positive |
| 14 | Negative | Positive |
| 15 | Negative | Positive |
| 16 | Negative | Positive |
| 17 | Negative | Positive |
| 18 | Negative | Positive |
| 19 | Negative | Positive |
| 20 | Negative | Positive |
| 21 | Negative | Positive |
| Overlap | No | No |
| Relative to C/O | All 21 below C/O | All 21 above C/O |
Qualitative Data for 150 ng/mL cutoff
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| Replicates | 225 ng/mL(n=21) | 375 ng/mL(n=21) |
|---|---|---|
| 1 | Negative | Positive |
| 2 | Negative | Positive |
| 3 | Negative | Positive |
| 4 | Negative | Positive |
| 5 | Negative | Positive |
| 6 | Negative | Positive |
| 7 | Negative | Positive |
| 8 | Negative | Positive |
| 9 | Negative | Positive |
| 10 | Negative | Positive |
| 11 | Negative | Positive |
| 12 | Negative | Positive |
| 13 | Negative | Positive |
| 14 | Negative | Positive |
| 15 | Negative | Positive |
| 16 | Negative | Positive |
| 17 | Negative | Positive |
| 18 | Negative | Positive |
| 19 | Negative | Positive |
| 20 | Negative | Positive |
| 21 | Negative | Positive |
| Overlap | No | No |
| Relative to C/O | All 21 below C/O | All 21 above C/O |
Qualitative Data for 300 ng/mL cutoff
c) Analytical Recovery and Linearity
Linearity studies were performed in accordance with CLSI Guideline EP06-A. To demonstrate the dilution linearity for purposes of sample dilution and quality control of the entire assay range, drug free urine was spiked to the high level calibrator using Benzoylecgonine (Cocaine Metabolite) (1000 ng/mL) and diluted with drug free urine to generate 9 intermediate levels.
Each sample was run in replicates of five in semi-quantitative mode and the average was used to determine percent recovery compared to the expected target value. The percent recovery is summarized in the table below.
| Level | ExpectedConcentration(ng/mL) | ObservedConcentration(ng/mL) | Recovery (%) |
|---|---|---|---|
| 1 | 0 | 0.6 | N/A |
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| Level | ExpectedConcentration(ng/mL) | ObservedConcentration(ng/mL) | Recovery (%) |
|---|---|---|---|
| 2 | 102.5 | 103.6 | 101.1 |
| 3 | 205.0 | 213.6 | 104.2 |
| 4 | 307.5 | 294.8 | 95.9 |
| 5 | 410.0 | 413.8 | 100.9 |
| 6 | 512.5 | 510.4 | 99.6 |
| 7 | 615.0 | 640.6 | 104.2 |
| 8 | 717.5 | 781.4 | 108.9 |
| 9 | 820.0 | 880.0 | 107.3 |
| 10 | 922.5 | 952.0 | 103.2 |
| 11 | 1025.0 | 1025.0 | 100.0 |
d) Method Comparison and Accuracy
The method comparison study was performed in accordance with CLSI Guideline EP09-A3. One hundred patient samples were analyzed by the DRI Cocaine Metabolite Assay in both qualitative and semi-quantitative modes and the results were compared to LC-MS/MS. The overall concordance between LC-MS/MS and DRI Cocaine Metabolite Assay is 100%. The qualitative and semi-quantitative results for both cutoffs are summarized in the tables below.
Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff
| CandidateDeviceResults | Negativeby LC-MS/MS | < 50% ofCutoffconcentrationby LC-MS/MS(< 75 ng/mL) | Near CutoffNegative(Between 50%below the cutoffand the cutoffconcentration asdetermined byLC-MS/MS)(75-149 ng/mL) | Near CutoffPositive(Between thecutoff and 50%above the cutoffconcentration asdetermined byLC-MS/MS)(150-225 ng/mL) | High Positives(Greater than50% abovecutoffconcentration(> 225 ng/mL) |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
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Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff
| CandidateDeviceResults | Negativeby LC-MS/MS | < 50% ofCutoffconcentrationby LC-MS/MS(< 150 ng/mL) | Near CutoffNegative(Between 50%below the cutoffand the cutoffconcentration asdetermined byLC-MS/MS)(150-299ng/mL) | Near CutoffPositive(Between thecutoff and 50%above the cutoffconcentration asdetermined byLC-MS/MS)(300-450 ng/mL) | High Positives(Greater than50% abovecutoffconcentration(> 450 ng/mL) |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
Qualitative Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff
| CandidateDeviceResults | Negativeby LC-MS/MS | < 50% ofCutoffconcentrationby LC-MS/MS(< 75 ng/mL) | Near CutoffNegative(Between 50%below the cutoffand the cutoffconcentration asdetermined byLC-MS/MS)(75 - 149ng/mL) | Near CutoffPositive(Between thecutoff and 50%above the cutoffconcentration asdetermined byLC-MS/MS)(150-225 ng/mL) | High Positives(Greater than50% abovecutoffconcentration(> 225 ng/mL) |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
Qualitative Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff
{12}------------------------------------------------
| CandidateDeviceResults | Negativeby LC-MS/MS | < 50% ofCutoffconcentrationby LC-MS/MS(< 150 ng/mL) | Near CutoffNegative(Between 50%below thecutoff and thecutoffconcentrationas determinedby LC-MS/MS)(150-299ng/mL) | Near CutoffPositive(Between thecutoff and 50%above the cutoffconcentration asdetermined byLC-MS/MS)(300-450ng/mL) | High Positives(Greater than50% abovecutoffconcentration(> 450 ng/mL) |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100%
Agreement among Negative: 50/50 = 100%
e) Specificity
The cross-reactivity of Cocaine and its metabolites were evaluated by adding known amounts of each compound to drug-free negative urine. The results are summarized in the tables below.
| Cocaine and metabolites | Tested Concentration(ng/mL) | Cross-reactivity(%) |
|---|---|---|
| Benzoylecgonine | 150 | 100 |
| Cocaine | 25,000 | 0.6 |
| Cocaethylene | 30,000 | 0.5 |
| Ecgonine | 90,000 | 0.17 |
| Ecgonine Methyl Ester | 100,000 | <0.15 |
| m-hydroxybenzoylecgonine | 300 | 50 |
| Norcocaine | 100,000 | <0.15 |
Cross reactivity of Cocaine and its metabolites for 150 ng/mL cut off
Cross reactivity of Cocaine and its metabolites for 300 ng/mL cut-off
| Cocaine and metabolites | Tested Concentration(ng/mL) | Cross-reactivity(%) |
|---|---|---|
| Benzoylecgonine | 300 | 100 |
| Cocaine | 50,000 | 0.6 |
| Cocaethylene | 60,000 | 0.5 |
| Ecgonine | 160,000 | 0.19 |
| Ecgonine Methyl Ester | 100,000 | <0.3 |
| m-hydroxybenzoylecgonine | 600 | 50 |
| Norcocaine | 100,000 | <0.3 |
Structurally unrelated compounds were evaluated by adding each substance to Benzoylecgonine spiked at 112.5 ng/mL (-25% of the 150 ng/mL cutoff concentration), 187.5 ng/mL (+25% of the 150
{13}------------------------------------------------
ng/mL cutoff concentration), 225 ng/mL (-25% of the 300 ng/mL cutoff concentration) and 375 ng/mL (+25% of the 300 ng/mL cutoff concentration), at the concentrations indicated. As shown in the table below, the controls were detected accurately, low control as negative and the high control as positive, indicating that all the compounds evaluated exhibited no significant cross-reactivity at the concentrations tested.
| TestedConcentration | Spiked Benzoylecgonine Level | ||
|---|---|---|---|
| Structurally Unrelated | Low Control | High Control | |
| Compounds | (ng/mL) | Positive/Negative | Positive/Negative |
| 11-nor-Δ9 -THC-COOH | 100,000 | Negative | Positive |
| 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive |
| 1S,2R(+)-Ephedrine | 100,000 | Negative | Positive |
| Acetaminophen | 1,000,000 | Negative | Positive |
| Acetylsalicylic acid | 1,000,000 | Negative | Positive |
| Acyclovir | 75,000 | Negative | Positive |
| Albuterol | 1,000,000 | Negative | Positive |
| Amikacin | 1,000,000 | Negative | Positive |
| Amitriptyline | 100,000 | Negative | Positive |
| Amobarbital | 100,000 | Negative | Positive |
| Amoxicillin | 1,000,000 | Negative | Positive |
| Amphetamine | 1,000,000 | Negative | Positive |
| Azithromycin | 75,000 | Negative | Positive |
| Benzocaine | 1,000,000 | Negative | Positive |
| Buprenorphine | 100,000 | Negative | Positive |
| Bupropion | 100,000 | Negative | Positive |
| Caffeine | 100,000 | Negative | Positive |
| Calcium Carbonate | 5,000,000 | Negative | Positive |
| Carbamazepine | 100,000 | Negative | Positive |
| Carisoprodol | 100,000 | Negative | Positive |
| Chlorpromazine | 500,000 | Negative | Positive |
| Chlorzoxazone | 1,000,000 | Negative | Positive |
| cis-Tramadol | 1,000,000 | Negative | Positive |
| Clomipramine | 100,000 | Negative | Positive |
| Clonidine | 100,000 | Negative | Positive |
| Codeine | 1,000,000 | Negative | Positive |
| Cotinine | 100,000 | Negative | Positive |
| Dapsone | 100,000 | Negative | Positive |
| Desipramine | 100,000 | Negative | Positive |
| Dextromethorphan | 100,000 | Negative | Positive |
| Dihydrocodeine | 100,000 | Negative | Positive |
| Diphenhydramine | 1,000,000 | Negative | Positive |
| TestedConcentration(ng/mL) | Spiked Benzoylecgonine Level | ||
| Structurally UnrelatedCompounds | Low ControlPositive/Negative | High ControlPositive/Negative | |
| Doxepine | 500,000 | Negative | Positive |
| Doxycycline Hyclate | 100,000 | Negative | Positive |
| EDDP | 100,000 | Negative | Positive |
| Ethyl β-D-glucuronide | 100,000 | Negative | Positive |
| Fentanyl | 100,000 | Negative | Positive |
| Fluconazole | 100,000 | Negative | Positive |
| Fluoxetine | 50,000 | Negative | Positive |
| Gabapentin | 100,000 | Negative | Positive |
| Gentamicin | 100,000 | Negative | Positive |
| Haloperidol | 100,000 | Negative | Positive |
| Heroin | 100,000 | Negative | Positive |
| Hydrocodone | 100,000 | Negative | Positive |
| Hydromorphone | 100,000 | Negative | Positive |
| Hydroxyzine | 100,000 | Negative | Positive |
| Hyoscyamine HCl | 75,000 | Negative | Positive |
| Ibuprofen | 5,000,000 | Negative | Positive |
| Imipramine | 100,000 | Negative | Positive |
| Indomethacin | 75,000 | Negative | Positive |
| Lamotrigine | 1,000,000 | Negative | Positive |
| Levofloxacin | 75,000 | Negative | Positive |
| Lidocaine | 1,000,000 | Negative | Positive |
| Lithium heparin | 5,000,000 | Negative | Positive |
| Loratadine | 500,000 | Negative | Positive |
| LSD | 100,000 | Negative | Positive |
| Maprotiline | 100,000 | Negative | Positive |
| Meperidine | 1,000,000 | Negative | Positive |
| Mesoridazine | 1,000,000 | Negative | Positive |
| Methadone | 1,000,000 | Negative | Positive |
| Methamphetamine | 100,000 | Negative | Positive |
| Methylphenidate | 100,000 | Negative | Positive |
| Metoclopramide | 1,000,000 | Negative | Positive |
| Metronidazole | 100,000 | Negative | Positive |
| Morphine | 200,000 | Negative | Positive |
| Morphine-3β-D-glucuronide | 100,000 | Negative | Positive |
| Morphine-6β-D-glucuronide | 100,000 | Negative | Positive |
| Nalbuphine | 1,000,000 | Negative | Positive |
| Nalorphine | 100,000 | Negative | Positive |
| Naloxone | 100,000 | Negative | Positive |
| Naltrexone | 1,000,000 | Negative | Positive |
| Spiked Benzoylecgonine Level | |||
| Structurally UnrelatedCompounds | TestedConcentration(ng/mL) | Low ControlPositive/Negative | High ControlPositive/Negative |
| Naproxen | 5,000,000 | Negative | Positive |
| Nitrazepam | 100,000 | Negative | Positive |
| Norbuprenorphine | 100,000 | Negative | Positive |
| Norcodeine | 100,000 | Negative | Positive |
| Nordiazepam | 100,000 | Negative | Positive |
| Norfluoxetine HCl | 1,000,000 | Negative | Positive |
| Norketamine | 100,000 | Negative | Positive |
| Norproxyphene | 100,000 | Negative | Positive |
| Nortriptyline | 100,000 | Negative | Positive |
| Ofloxacin | 100,000 | Negative | Positive |
| Omeprazole | 75,000 | Negative | Positive |
| Oxazepam | 1,000,000 | Negative | Positive |
| Oxycodone | 100,000 | Negative | Positive |
| Oxymorphone | 100,000 | Negative | Positive |
| Paroxetine | 100,000 | Negative | Positive |
| PCP | 1,000,000 | Negative | Positive |
| Phenelzine | 75,000 | Negative | Positive |
| Phenobarbital | 1,000,000 | Negative | Positive |
| Promethazine | 100,000 | Negative | Positive |
| Propoxyphene | 750,000 | Negative | Positive |
| Ranitidine | 100,000 | Negative | Positive |
| Risperidone | 100,000 | Negative | Positive |
| Scopolamine | 1,000,000 | Negative | Positive |
| Secobarbital | 1,000,000 | Negative | Positive |
| Sertraline | 100,000 | Negative | Positive |
| Spironolactone | 750,000 | Negative | Positive |
| Stavudine | 100,000 | Negative | Positive |
| Tapentadol | 100,000 | Negative | Positive |
| Terbinafine | 750,000 | Negative | Positive |
| Thiopental | 1,000,000 | Negative | Positive |
| Thioridazine | 750,000 | Negative | Positive |
| Tobramycin | 1,000,000 | Negative | Positive |
| Tolmetin | 750,000 | Negative | Positive |
| Trazodone | 1,000,000 | Negative | Positive |
| Trimethoprim | 1,000,000 | Negative | Positive |
| Vancomycin | 1,000,000 | Negative | Positive |
| Venlafaxine | 1,000,000 | Negative | Positive |
| Verapamil | 100,000 | Negative | Positive |
| Zolpidem Tartrate | 100,000 | Negative | Positive |
Structurally unrelated compounds spiked at the concentration listed below into Low and High control urine for 150 ng/mL cut-off
{14}------------------------------------------------
{15}------------------------------------------------
{16}------------------------------------------------
| Spiked Benzoylecgonine Level | |||
|---|---|---|---|
| Structurally UnrelatedCompounds | TestedConcentration(ng/mL) | Low ControlPositive/Negative | High ControlPositive/Negative |
| 11-nor-Δ 9-THC-COOH | 100,000 | Negative | Positive |
| 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive |
| 1S,2R(+)-Ephedrine | 100.000 | Negative | Positive |
| Acetaminophen | 1,000,000 | Negative | Positive |
| Acetylsalicylic acid | 1,000,000 | Negative | Positive |
| Acyclovir | 75,000 | Negative | Positive |
| Albuterol | 1,000,000 | Negative | Positive |
| Amikacin | 1,000,000 | Negative | Positive |
| Amitriptyline | 100,000 | Negative | Positive |
| Amobarbital | 100,000 | Negative | Positive |
| Amoxicillin | 1,000,000 | Negative | Positive |
| Amphetamine | 1,000,000 | Negative | Positive |
| Azithromycin | 75,000 | Negative | Positive |
| Benzocaine | 1,000,000 | Negative | Positive |
| Buprenorphine | 100,000 | Negative | Positive |
| Bupropion | 100,000 | Negative | Positive |
| Caffeine | 100,000 | Negative | Positive |
| Calcium Carbonate | 5,000,000 | Negative | Positive |
| Carbamazepine | 100,000 | Negative | Positive |
| Carisoprodol | 100,000 | Negative | Positive |
| Chlorpromazine | 500,000 | Negative | Positive |
| Chlorzoxazone | 1,000,000 | Negative | Positive |
| cis-Tramadol | 1,000,000 | Negative | Positive |
| Clomipramine | 100,000 | Negative | Positive |
| Clonidine | 100,000 | Negative | Positive |
| Codeine | 1,000,000 | Negative | Positive |
| Cotinine | 100,000 | Negative | Positive |
| Dapsone | 100,000 | Negative | Positive |
| Desipramine | 100,000 | Negative | Positive |
| Dextromethorphan | 100,000 | Negative | Positive |
| Dihydrocodeine | 100,000 | Negative | Positive |
| Diphenhydramine | 1,000,000 | Negative | Positive |
| Doxepine | 500,000 | Negative | Positive |
| Doxycycline Hyclate | 100,000 | Negative | Positive |
| EDDP | 100,000 | Negative | Positive |
| Ethyl β-D-glucuronide | 100,000 | Negative | Positive |
| Fentanyl | 100,000 | Negative | Positive |
| Fluconazole | 100,000 | Negative | Positive |
| Spiked Benzoylecgonine Level | |||
| Structurally UnrelatedCompounds | TestedConcentration(ng/mL) | Low ControlPositive/Negative | High ControlPositive/Negative |
| Fluoxetine | 50,000 | Negative | Positive |
| Gabapentin | 100,000 | Negative | Positive |
| Gentamicin | 100,000 | Negative | Positive |
| Haloperidol | 100,000 | Negative | Positive |
| Heroin | 100,000 | Negative | Positive |
| Hydrocodone | 100,000 | Negative | Positive |
| Hydromorphone | 100,000 | Negative | Positive |
| Hydroxyzine | 100,000 | Negative | Positive |
| Hyoscyamine HCl | 75,000 | Negative | Positive |
| Ibuprofen | 5,000,000 | Negative | Positive |
| Imipramine | 100,000 | Negative | Positive |
| Indomethacin | 75,000 | Negative | Positive |
| Lamotrigine | 1,000,000 | Negative | Positive |
| Levofloxacin | 75,000 | Negative | Positive |
| Lidocaine | 1,000,000 | Negative | Positive |
| Lithium heparin | 5,000,000 | Negative | Positive |
| Loratadine | 500,000 | Negative | Positive |
| LSD | 100,000 | Negative | Positive |
| Maprotiline | 100,000 | Negative | Positive |
| Meperidine | 1,000,000 | Negative | Positive |
| Mesoridazine | 1,000,000 | Negative | Positive |
| Methadone | 1,000,000 | Negative | Positive |
| Methamphetamine | 100,000 | Negative | Positive |
| Methylphenidate | 100,000 | Negative | Positive |
| Metoclopramide | 1,000,000 | Negative | Positive |
| Metronidazole | 100,000 | Negative | Positive |
| Morphine | 200,000 | Negative | Positive |
| Morphine-3β-D-glucuronide | 100,000 | Negative | Positive |
| Morphine-6β-D-glucuronide | 100,000 | Negative | Positive |
| Nalbuphine | 1,000,000 | Negative | Positive |
| Nalorphine | 100,000 | Negative | Positive |
| Naloxone | 100,000 | Negative | Positive |
| Naltrexone | 1,000,000 | Negative | Positive |
| Naproxen | 5,000,000 | Negative | Positive |
| Nitrazepam | 100,000 | Negative | Positive |
| Norbuprenorphine | 100,000 | Negative | Positive |
| Norcodeine | 100,000 | Negative | Positive |
| Nordiazepam | 100,000 | Negative | Positive |
| Norfluoxetine HCl | 1,000,000 | Negative | Positive |
| TestedConcentration(ng/mL) | Spiked Benzoylecgonine Level | ||
| Structurally UnrelatedCompounds | Low ControlPositive/Negative | High ControlPositive/Negative | |
| Norketamine | 100,000 | Negative | Positive |
| Norproxyphene | 100,000 | Negative | Positive |
| Nortriptyline | 100,000 | Negative | Positive |
| Ofloxacin | 100,000 | Negative | Positive |
| Omeprazole | 75,000 | Negative | Positive |
| Oxazepam | 1,000,000 | Negative | Positive |
| Oxycodone | 100,000 | Negative | Positive |
| Oxymorphone | 100,000 | Negative | Positive |
| Paroxetine | 100,000 | Negative | Positive |
| PCP | 1,000,000 | Negative | Positive |
| Phenelzine | 75,000 | Negative | Positive |
| Phenobarbital | 1,000,000 | Negative | Positive |
| Promethazine | 100,000 | Negative | Positive |
| Propoxyphene | 750,000 | Negative | Positive |
| Ranitidine | 100,000 | Negative | Positive |
| Risperidone | 100,000 | Negative | Positive |
| Scopolamine | 1,000,000 | Negative | Positive |
| Secobarbital | 1,000,000 | Negative | Positive |
| Sertraline | 100,000 | Negative | Positive |
| Spironolactone | 750,000 | Negative | Positive |
| Stavudine | 100,000 | Negative | Positive |
| Tapentadol | 100,000 | Negative | Positive |
| Terbinafine | 750,000 | Negative | Positive |
| Thiopental | 1,000,000 | Negative | Positive |
| Thioridazine | 750,000 | Negative | Positive |
| Tobramycin | 1,000,000 | Negative | Positive |
| Tolmetin | 750,000 | Negative | Positive |
| Trazodone | 1,000,000 | Negative | Positive |
| Trimethoprim | 1,000,000 | Negative | Positive |
| Vancomycin | 1,000,000 | Negative | Positive |
| Venlafaxine | 1,000,000 | Negative | Positive |
| Verapamil | 100,000 | Negative | Positive |
| Zolpidem Tartrate | 100,000 | Negative | Positive |
Structurally unrelated compounds spiked at the concentration listed below into Low and High control urine for 300 ng/mL cut-off
{17}------------------------------------------------
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f) Interference
The interference studies were performed in accordance with CLSI Guideline EP07-A2, using both qualitative and semi-quantitative modes. The potential interference of pH, endogenous and exogenous physiologic substances on recovery of Benzoylecgonine using DRI Cocaine Metabolite Assay was assessed by spiking known compounds of potentially interfering substances into the low control, 112.5 ng/mL (-25% of the cutoff concentration of 150 ng/mL)
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and 225 ng/mL (-25% of the cutoff concentration of 300 ng/mL) and high control, 187.5 ng/mL (+25% of the cutoff concentration of 150 ng/mL) and 375 ng/mL (+25% of the cutoff concentration of 300 ng/mL). In the presence of the compounds listed below, the controls were detected accurately, indicating that these compounds did not show interference in the assay.
| Compound | Tested Concentration(mg/dL) | Spiked Benzoylecgonine Level | |
|---|---|---|---|
| Low Control-25% of cutoff(112.5 ng/mL) | High Control+25% of cutoff(187.5 ng/mL) | ||
| Acetaminophen | 10 | Negative | Positive |
| Acetone | 1000 | Negative | Positive |
| Ascorbic Acid | 1000 | Negative | Positive |
| Aspirin | 10 | Negative | Positive |
| Caffeine | 10 | Negative | Positive |
| Creatinine | 500 | Negative | Positive |
| Ethanol | 1000 | Negative | Positive |
| Galactose | 10 | Negative | Positive |
| y-Globulin | 500 | Negative | Positive |
| Glucose | 3000 | Negative | Positive |
| Hemoglobin | 150 | Negative | Positive |
| Human Serum Albumin | 500 | Negative | Positive |
| Ibuprofen | 10 | Negative | Positive |
| Oxalic Acid | 100 | Negative | Positive |
| Riboflavin | 7.5 | Negative | Positive |
| Sodium Chloride | 1000 | Negative | Positive |
| Urea | 1250 | Negative | Positive |
| pH | |||
| pH | 3 | Negative | Positive |
| pH | 4 | Negative | Positive |
| pH | 5 | Negative | Positive |
| pH | 6 | Negative | Positive |
| pH | 7 | Negative | Positive |
| pH | 8 | Negative | Positive |
| pH | 9 | Negative | Positive |
| pH | 10 | Negative | Positive |
| pH | 11 | Negative | Positive |
Interference substances for 150 ng/mL cut-off
Interference substances for 300 ng/mL cut-off
{20}------------------------------------------------
| Tested Concentration(mg/dL) | Spiked Benzoylecgonine Level | ||
|---|---|---|---|
| Compound | Low Control-25% of cutoff(225 ng/mL) | High Control+25% of cutoff(375 ng/mL) | |
| Acetaminophen | 10 | Negative | Positive |
| Acetone | 1000 | Negative | Positive |
| Ascorbic Acid | 1000 | Negative | Positive |
| Aspirin | 10 | Negative | Positive |
| Caffeine | 10 | Negative | Positive |
| Creatinine | 500 | Negative | Positive |
| Ethanol | 1000 | Negative | Positive |
| Galactose | 10 | Negative | Positive |
| γ-Globulin | 500 | Negative | Positive |
| Glucose | 3000 | Negative | Positive |
| Hemoglobin | 150 | Negative | Positive |
| Human Serum Albumin | 500 | Negative | Positive |
| Ibuprofen | 10 | Negative | Positive |
| Oxalic Acid | 100 | Negative | Positive |
| Riboflavin | 7.5 | Negative | Positive |
| Sodium Chloride | 1000 | Negative | Positive |
| Urea | 1250 | Negative | Positive |
| pH | 3 | Negative | Positive |
| pH | 4 | Negative | Positive |
| pH | 5 | Negative | Positive |
| pH | 6 | Negative | Positive |
| pH | 7 | Negative | Positive |
| pH | 8 | Negative | Positive |
| pH | 9 | Negative | Positive |
| pH | 10 | Negative | Positive |
| pH | 11 | Negative | Positive |
| Spiked Benzoylecgonine Level | |||
| Specific Gravity | Low Control | High Control | |
| 1.004 | Negative | Positive | |
| 1.005 | Negative | Positive | |
| 1.007 | Negative | Positive | |
| 1.010 | Negative | Positive | |
| 1.011 | Negative | Positive | |
| 1.013 | Negative | Positive | |
| 1.019 | Negative | Positive | |
| 1.023 | Negative | Positive | |
| 1.025 | Negative | Positive | |
| 1.029 | Negative | Positive |
g) Specific Gravity
Drug free urine samples with specific gravity ranging in value within 1.000 to 1.030 were split and spiked with Benzoylecgonine to a final concentration of either 112.5 ng/mL or 225 ng/mL (the low control concentrations) or 187.5 ng/mL or 375 ng/mL (high control concentrations).
{21}------------------------------------------------
These samples were then evaluated in both qualitative and semi-quantitative modes. The controls were detected accurately, indicating that no interference was observed.
Specific gravity interference data for 150 ng/mL cut-off
Specific gravity interference data for 300 ng/mL cut-off
{22}------------------------------------------------
| Specific Gravity | Spiked Benzoylecgonine Level | |
|---|---|---|
| Low Control | High Control | |
| 1.004 | Negative | Positive |
| 1.005 | Negative | Positive |
| 1.007 | Negative | Positive |
| 1.010 | Negative | Positive |
| 1.011 | Negative | Positive |
| 1.013 | Negative | Positive |
| 1.019 | Negative | Positive |
| 1.023 | Negative | Positive |
| 1.025 | Negative | Positive |
| 1.029 | Negative | Positive |
{23}------------------------------------------------
H. Conclusion
The information supports a determination of substantial equivalence between DRI Cocaine Metabolite Assay and the predicate device Cocaine Metabolite Enzyme Immunoassay (K960187).
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).