(58 days)
The LZI Oxycodone III Enzyme Immunoassay is intended for the quantitative determination of oxycodone in human urine at the cutoff values of 100 ng/mL when calibrated against oxycodone. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC/MS or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatograpy and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Oxycodone III Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available oxycodone standard and referred to as oxycodone-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, oxycodone-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound oxycodone-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Oxycodone III Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2, which are bottled separately but sold together within the kit. The LZI Oxycodone III Enzyme Immunoassay is traceable to a commercially available oxycodone standard.
The Ri solution contains mouse monoclonal anti-oxycodone antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with oxycodone in buffer with sodium azide (0.09 %) as a preservative.
The document provided describes the LZI Oxycodone III Enzyme Immunoassay, a device for detecting oxycodone in human urine. This is a chemical assay, not an AI/ML-based device. Therefore, many of the requested criteria related to AI/ML or imaging studies (like number of experts, adjudication methods, MRMC studies, training/test set sample sizes, and ground truth establishment for AI/ML models) are not applicable.
However, I can extract and present the acceptance criteria for a chemical assay and the study that proves the device meets those criteria based on the provided text.
Device Name: LZI Oxycodone III Enzyme Immunoassay
Device Type: Homogeneous enzyme immunoassay (chemical assay)
Intended Use: Qualitative and semi-quantitative determination of oxycodone in human urine at cutoff values of 100 ng/mL and 300 ng/mL. The assay provides only a preliminary analytical result, requiring a more specific alternative chemical method (e.g., GC/MS or LC/MS) for confirmation.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for a chemical assay are typically defined by performance characteristics such as precision, analytical recovery, accuracy (method comparison with a gold standard), cross-reactivity, and interference studies.
Cutoff 1: 100 ng/mL
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred from study design) | Reported Device Performance and Study Results |
|---|---|---|
| Precision | Consistent results (negative/positive) for samples at various concentrations around the cutoff. For 100 ng/mL cutoff, typically 100% agreement for concentrations ± 25% and 100% agreement for concentrations further from cutoff, with some expected variability at the cutoff itself. | Within Run (N=22 determinations):- 0-75 ng/mL: 100% Negative- 125-200 ng/mL: 100% Positive- 100 ng/mL: 5 Neg / 17 Pos (Semi-quantitative), 9 Neg / 13 Pos (Qualitative)Total Precision (N=88 determinations):- 0-75 ng/mL: 100% Negative- 125-200 ng/mL: 100% Positive- 100 ng/mL: 26 Neg / 62 Pos (Semi-quantitative), 33 Neg / 55 Pos (Qualitative) |
| Analytical Recovery | Determined concentration should be within a specified percentage of the target concentration across the assay range. | Performed across a range of 0-300 ng/mL by serial dilution of a 300 ng/mL spiked sample. Average % Recovery ranged from 90.3% to 110.0% for concentrations 30-300 ng/mL. The 0 ng/mL sample showed 0.7 ng/mL determined average. |
| Method Comparison (Accuracy) | High agreement with a confirmatory method (LC/MS) across different concentration ranges (negative, near cutoff negative/positive, high positive). | Clinical Samples (N=82), compared to LC/MS:Semi-Quantitative Results:- Positive agreement: 90.2% (2 discordants in "Near Cutoff Negative" range, 4 discordants in "Near Cutoff Positive" range)- Negative agreement: 95.1% (4 discordants in "Near Cutoff Positive" range)Qualitative Accuracy Study (same data):- Positive agreement: 90.2%- Negative agreement: 95.1%Discordant samples often contained oxymorphone, indicating potential cross-reactivity or combined effect of oxycodone and its metabolite. |
| Cross-reactivity | Low or no cross-reactivity with structurally unrelated compounds and expected cross-reactivity with major metabolites and structurally related compounds. | Oxycodone & Major Metabolites:- Oxycodone, Oxymorphone: 100.00%- Noroxycodone: 0.40%- Noroxymorphone: 0.17%Structurally Related Compounds: Hydrocodone (0.40%), Hydromorphone (0.40%), Oxymorphone-3β-D-Glucuronide (43.48%). Most others (e.g., Codeine, Morphine, Buprenorphine, Naloxone) showed ND (Not Detected) at 100,000 ng/mL. The study confirmed expected positive and negative results at ±25% of cutoff for various other pharmacological compounds. |
| Interference (Endogenous & Preservative) | No significant interference observed with common endogenous substances or preservatives at relevant concentrations. | No significant interference observed for most compounds (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Urea, etc.) at tested concentrations (up to 6000 mg/dL).Boric Acid: Showed interference at 1000 mg/dL at ±25% of cutoff (Negative result for both 75 ng/mL and 125 ng/mL oxycodone samples), but not at ±50% of cutoff. This indicates a potential suppression of the signal by high concentrations of boric acid. |
| Specific Gravity Interference | No deviations from expected results over a range of specific gravity values. | No deviations from expected positive or negative results across specific gravity 1.000 to 1.030 when spiked at ±25% of cutoff (75 ng/mL and 125 ng/mL oxycodone). |
| pH Interference | No deviations from expected results over a physiological pH range. | No deviations from expected results across pH levels from 3 to 11 when spiked at ±25% of cutoff (75 ng/mL and 125 ng/mL oxycodone). |
Cutoff 2: 300 ng/mL
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred from study design) | Reported Device Performance and Study Results |
|---|---|---|
| Precision | Consistent results (negative/positive) for samples at various concentrations around the cutoff. For 300 ng/mL cutoff, similar criteria as above. | Within Run (N=22 determinations):- 0-225 ng/mL: 100% Negative- 375-600 ng/mL: 100% Positive- 300 ng/mL: 6 Neg / 16 Pos (Semi-quantitative), 10 Neg / 12 Pos (Qualitative)Total Precision (N=88 determinations):- 0-225 ng/mL: 100% Negative- 375-600 ng/mL: 100% Positive- 300 ng/mL: 27 Neg / 61 Pos (Semi-quantitative), 40 Neg / 48 Pos (Qualitative) |
| Analytical Recovery | Determined concentration should be within a specified percentage of the target concentration across the assay range. | Performed across a range of 0-800 ng/mL by serial dilution of an 800 ng/mL spiked sample. Average % Recovery ranged from 104.5% to 111.5% for concentrations 80-800 ng/mL. The 0 ng/mL sample showed 0.3 ng/mL determined average. |
| Method Comparison (Accuracy) | High agreement with a confirmatory method (LC/MS) across different concentration ranges. | Clinical Samples (N=90), compared to LC/MS:Semi-Quantitative Results:- Positive agreement: 97.8% (2 discordants in "Near Cutoff Negative" range, 1 discordant in "Near Cutoff Positive" range)- Negative agreement: 95.6% (1 discordant in "Near Cutoff Positive" range)Qualitative Accuracy Study (same data):- Positive agreement: 95.6%- Negative agreement: 95.6%Discordant samples often involved significant oxymorphone concentrations relative to oxycodone. |
| Cross-reactivity | Low or no cross-reactivity with structurally unrelated compounds and expected cross-reactivity with major metabolites and structurally related compounds. | Oxycodone & Major Metabolites:- Oxycodone, Oxymorphone: 100.00%- Noroxycodone: 0.40%- Noroxymorphone: ND (Not Detected) at 100,000 ng/mL.Structurally Related Compounds: Hydrocodone (0.40%), Hydromorphone (0.40%), Oxymorphone-3β-D-Glucuronide (42.86%). Most others (e.g., Codeine, Morphine, Buprenorphine, Naloxone) showed ND at 100,000 ng/mL. The study confirmed expected positive and negative results at ±25% of cutoff for various other pharmacological compounds. |
| Interference (Endogenous & Preservative) | No significant interference observed with common endogenous substances or preservatives at relevant concentrations. | No significant interference observed for most compounds (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Urea, etc.) at tested concentrations (up to 6000 mg/dL).Boric Acid: Showed interference at 1000 mg/dL at ±25% of cutoff (Negative result for both 225 ng/mL and 375 ng/mL oxycodone samples), but for 300 ng/mL cutoff, it showed Negative at 150 ng/mL and Positive at 450 ng/mL, indicating it might behave differently at higher concentrations or different % of cutoff. |
| Specific Gravity Interference | No deviations from expected results over a range of specific gravity values. | No deviations from expected positive or negative results across specific gravity 1.000 to 1.030 when spiked at ±25% of cutoff (225 ng/mL and 375 ng/mL oxycodone). |
| pH Interference | No deviations from expected results over a physiological pH range. | No deviations from expected results across pH levels from 3 to 11 when spiked at ±25% of cutoff (225 ng/mL and 375 ng/mL oxycodone). |
Study Details:
As this is a chemical immunoassay and not an AI/ML device, certain questions are not relevant. However, I will answer the applicable points:
2. Sample sizes used for the test set and data provenance:
- Test set (Clinical Samples for Method Comparison):
- 100 ng/mL Cutoff: 82 unaltered clinical samples
- 300 ng/mL Cutoff: 90 unaltered clinical samples
- Precision Studies: Spiked pooled negative urine samples, tested in replicates, resulting in 88 total determinations per concentration level across 22 days.
- Analytical Recovery Studies: Serially diluted spiked pooled negative urine, each sample run in 10 replicates.
- Cross-reactivity and Interference Studies: Spiked pooled negative human urine, tested in duplicates.
- Data Provenance: Not explicitly stated, but clinical samples typically imply real-world specimens. The location (country of origin) and retrospective/prospective nature are not specified in this summary.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable as the ground truth for this chemical assay was established by a well-defined analytical standard: Liquid Chromatography–Mass Spectrometry (LC/MS), which is considered a gold standard for drug quantitative analysis in urine. This is a laboratory-based, objective ground truth, not reliant on human expert interpretation of images or other subjective data.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. Ground truth for chemical assays is based on quantitative analytical methods (LC/MS), not on expert consensus or adjudication.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is a standalone chemical immunoassay, not an AI-assisted diagnostic tool that involves human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics described (Precision, Analytical Recovery, Method Comparison, Cross-reactivity, Interference, Specific Gravity, pH Interference) represent the standalone performance of the LZI Oxycodone III Enzyme Immunoassay. The device generates a quantitative or semi-quantitative result directly from the sample. Humans are involved in operating the automated clinical chemistry analyzer and interpreting the results, but a "human-in-the-loop" performance study as typically understood for AI models (e.g., radiologists interpreting images with or without AI guidance) is not relevant here.
7. The type of ground truth used:
- Confirmed Analytical Result: Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). For the method comparison studies, LC/MS was explicitly stated as the confirmation method for oxycodone and oxymorphone concentrations.
8. The sample size for the training set:
- Not applicable. This is a laboratory-developed and validated chemical assay, not an AI/ML model that requires a "training set" in the machine learning sense. The assay's parameters (e.g., reagent concentrations, antibody specificity) are developed and optimized through traditional biochemical and analytical chemistry methods, rather than by training on a dataset.
9. How the ground truth for the training set was established:
- Not applicable for the same reason as #8. The "ground truth" for developing such a chemical assay lies in analytical chemistry principles and the use of well-characterized reference standards and controls to determine its performance characteristics.
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September 17, 2020
Lin-Zhi International, Inc. Bernice Lin VP of Operations 2945 Oakmead Village Court Santa Clara, CA 95051
Re: K202007
Trade/Device Name: LZI Oxycodone III Enzyme Immunoassay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: DJG Dated: July 17, 2020 Received: July 21, 2020
Dear Bernice Lin:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing 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
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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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K202007
Device Name
LZI Oxycodone III Enzyme Immunoassay
Indications for Use (Describe)
The LZI Oxycodone III Enzyme Immunoassay is intended for the quantitative determination of oxycodone in human urine at the cutoff values of 100 ng/mL when calibrated against oxycodone. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC/MS or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatograpy and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
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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510(k) Summary of Safety and Effectiveness
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number
Prepared On
September 14, 2020
Introduction
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter Name, Address, and Contact:
Lin-Zhi International, Inc. 2945 Oakmead Village Court Santa Clara, CA 95051 Phone: (408) 970-8811 Fax: (408) 970-9030 e-mail: bclin@lin-zhi.com
| Contact: | Bernice Lin, Ph.D. |
|---|---|
| VP of Operations |
Device Name and Classification
| Classification Name: | Enzyme Immunoassay, OxycodoneClass II, DJG (91 Toxicology)21 CFR 862.3650 |
|---|---|
| Common Name: | Oxycodone Enzyme Immunoassay |
| Proprietary Name: | LZI Oxycodone III Enzyme Immunoassay |
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Legally Marketed Predicate Device(s)
The LZI Oxycodone III Enzyme Immunoassay (EIA) is substantially equivalent to the LZI Oxycodone Assay (K120763) manufactured by Lin-Zhi International, Inc. (LZI). The LZI Oxycodone III Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.
Device Description
The LZI Oxycodone III Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available oxycodone standard and referred to as oxycodone-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, oxycodone-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound oxycodone-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Oxycodone III Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2, which are bottled separately but sold together within the kit. The LZI Oxycodone III Enzyme Immunoassay is traceable to a commercially available oxycodone standard.
The Ri solution contains mouse monoclonal anti-oxycodone antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with oxycodone in buffer with sodium azide (0.09 %) as a preservative.
Intended Use
The LZI Oxycodone III Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of oxycodone in human urine at the cutoff values of 100 ng/mL and 300 ng/mL when calibrated against oxycodone. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC/MS or LC/MS, or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatograpy and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
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Comparison to Predicate Device
The LZI Oxycodone III Enzyme Immunoassay is substantially equivalent to the LZI Oxycodone Assay cleared by the FDA under the premarket notification K120763 for its stated intended use.
| DeviceCharacteristics | Subject Device | Predicate Device (K120763) |
|---|---|---|
| Intended Use | LZI Oxycodone III Enzyme ImmunoassayThe Lin-Zhi International, Inc. (LZI)Oxycodone III Enzyme Immunoassay isintended for the qualitative and semi-quantitative determination of oxycodone inhuman urine at a cutoff value of 100ng/mL and 300 ng/mL when calibratedagainst oxycodone. The assay is designedfor prescription use with a number ofautomated clinical chemistry analyzers.The semi-quantitative mode is forpurposes of (1) enabling laboratories todetermine an appropriate dilution of thespecimen for verification by aconfirmatory method such as GC/MS orLC/MS, or (2) permitting laboratories toestablish quality control procedures.The assay provides only a preliminaryanalytical result. A more specificalternative chemical confirmatorymethod (e.g., gas or liquidchromatography and massspectrometry) must be used to obtain aconfirmed analytical result (1, 2).Clinical consideration and professionaljudgment should be exercised with anydrug of abuse test result, particularlywhen the preliminary test result ispositive. | LZI Oxycodone Enzyme ImmunoassayThe Lin-Zhi International, Inc. (LZI)Oxycodone Enzyme Immunoassay isintended for the qualitative and semi-quantitative determination of oxycodonein human urine, at cutoff values of 100ng/mL and 300 ng/mL. The assay isdesigned for prescription use with anumber of automated clinical chemistryanalyzers.The assay provides only a preliminaryanalytical result. A more specificalternative analytical chemistry methodmust be used in order to obtain aconfirmed analytical result. Gas orLiquid Chromatography/MassSpectrometry (GC/MS or LC/MS) arethe preferred confirmatory methods.Clinical consideration and professionaljudgment should be exercised with anydrug of abuse test result, particularlywhen the preliminary test result ispositive. |
| Target Analyte | oxycodone | oxycodone |
| Cutoff | 100 ng/ and 300 ng/mL | 100 and 300 ng/mL |
| Matrix | Urine | Urine |
| Calibrator Levels | 100 ng/mL Cutoff: 5 Levels0, 50, 100, 150, and 300 ng/mL300 ng/mL Cutoff: 5 Levels0, 150, 300, 500, and 800 ng/mL | 0, 50, 100, 300, 500, and800 ng/mL |
The following table compares LZI Oxycodone III Enzyme Immunoassay with the predicate device.
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| DeviceCharacteristics | Subject Device | Predicate Device (K120763) |
|---|---|---|
| Control Levels | LZI Oxycodone III Enzyme Immunoassay | LZI Oxycodone Enzyme Immunoassay |
| 100 ng/mL Cutoff: 2 Levels75 and 125 ng/mL | 100 ng/mL Cutoff: 2 Levels75 and 125 ng/mL | |
| 300 ng/mL Cutoff: 2 Levels225 and 375 ng/mL | 300 ng/mL Cutoff: 2 Levels225 and 375 ng/mL | |
| Storage | 2-8 °C until expiration date |
Performance Characteristics Summary:
All validation studies below were conducted on the Beckman Coulter® AU480 Analyzer
Precision: 100 ng/mL Cutoff
The assay was tested in qualitative and semi-quantitative mode by spiking oxycodone into pooled negative urine at concentrations ±25 %, ±50 %, ±75 %, and ±100 % of the cutoff concentration.
Results shown below were obtained by testing all samples in replicate of two runs a day for 22 days on one Beckman Coulter AU480 automatic clinical analyzer for a total of 88 runs.
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| Oxycodone | % of Cutoff | Number of | Immunoassay | Number of | Immunoassay |
| Concentration | Determinations | Result | Determinations | Result | |
| 0 ng/mL | 0 % | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 25 % | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | 50 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 75 % | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100 % | 22 | 5 Neg / 17 Pos | 88 | 26 Neg / 62 Pos |
| 125 ng/mL | 125 % | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | 150 % | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | 175 % | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | 200 % | 22 | 22 Positive | 88 | 88 Positive |
Semi-Quantitative Positive/Negative Results:
Qualitative Positive/Negative Results:
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| Oxycodone | % of Cutoff | Number of | Immunoassay | Number of | Immunoassay |
| Concentration | Determinations | Result | Determinations | Result | |
| 0 ng/mL | 0 % | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 25 % | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | 50 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 75 % | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100 % | 22 | 9 Neg / 13 Pos | 88 | 33 Neg / 55 Pos |
| 125 ng/mL | 125 % | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | 150 % | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | 175 % | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | 200 % | 22 | 22 Positive | 88 | 88 Positive |
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Analytical Recovery: 100 ng/mL Cutoff
To demonstrate recovery of the entire assay range, a drug free-urine pool spiked with oxycodone at 300 ng/mL was serially diluted. Each sample was run in 10 replicates and the average was used to determine percent recovery compared to the expected target value. Results are summarized below:
| TargetConcentration(ng/mL) | DeterminedConcentration Range(ng/mL) | DeterminedConcentration Average(ng/mL) | Average% Recovery |
|---|---|---|---|
| 300 | 299.7 - 304.7 | 302.1 | 100.7 % |
| 270 | 277.5 - 287.4 | 282.7 | 104.7 % |
| 240 | 253.3 - 264.3 | 260.4 | 108.5 % |
| 210 | 219.8 - 241.2 | 231.0 | 110.0 % |
| 180 | 193.3 - 201.8 | 197.0 | 109.5 % |
| 150 | 149.1 - 158.7 | 153.6 | 102.4 % |
| 120 | 118.6 - 124.2 | 121.4 | 101.2 % |
| 90 | 86.3 - 90.7 | 88.8 | 98.6 % |
| 60 | 54.5 - 59.4 | 56.9 | 94.8 % |
| 30 | 25.7 - 29.5 | 27.1 | 90.3 % |
| 0 | -0.7 - 1.7 | 0.7 | N/A |
Method Comparison - Clinical Samples: 100 ng/mL Cutoff
A total of eighty-two (82) unaltered clinical samples were tested with the LZI Oxycodone III Enzyme Immunoassay on the Beckman Coulter AU480 automated clinical analyzer. All samples were tested in singlet.
Semi-Quantitative Results:
| OxycodoneResults100 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby LC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50% above thecutoffconcentration) | High Positive(Greater than50 % abovethe cutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 2* | 12 | 25 | 90.2 % |
| Negative | 20 | 9 | 10 | 4** | 0 | 95.1 % |
Discordant samples determined when comparing LC/MS oxycodone and oxymorphone results with EIA results on the Beckman Coulter AU480 automated clinical analyser are shown in the table below.
| Sample# | LC/MSOxycodone(ng/mL) | LC/MSOxymorphone(ng/mL) | TotalOxycodone +OxymorphoneLC/MS(ng/mL) |
|---|---|---|---|
| 37* | 35.5 | 54.4 | 89.9 |
| 38* | 46.4 | 44.6 | 91.0 |
| 42** | 0.0 | 102.7 | 102.7 |
| 43** | 2.2 | 104.8 | 107.0 |
{8}------------------------------------------------
| Sample# | LC/MSOxycodone(ng/mL) | LC/MSOxymorphone(ng/mL) | TotalOxycodone +OxymorphoneLC/MS(ng/mL) |
|---|---|---|---|
| 50** | 12.6 | 118.5 | 131.1 |
| 52** | 36.9 | 101.8 | 138.7 |
- Discordant between 50 % below cutoff and cutoff concentration (50 - 99.9 ng/mL)
** Discordant between cutoff and 50 % above cutoff concentration (100 - 149.9 ng/mL)
Qualitative Accuracy Study:
| OxycodoneResults100 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby LC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50% above thecutoffconcentration) | High Positive(Greater than50 % abovethe cutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 2* | 12 | 25 | 90.2 % |
| Negative | 20 | 9 | 10 | 4** | 0 | 95.1 % |
Discordant samples determined when comparing LC/MS oxycodone and oxymorphone results with EIA results on the Beckman Coulter AU480 automated clinical analyser are shown in the table below.
| Sample# | LC/MSOxycodone(ng/mL) | LC/MSOxymorphone(ng/mL) | TotalOxycodone +OxymorphoneLC/MS(ng/mL) |
|---|---|---|---|
| 37* | 35.5 | 54.4 | 89.9 |
| 38* | 46.4 | 44.6 | 91.0 |
| 42* | 0.0 | 102.7 | 102.7 |
| 43* | 2.2 | 104.8 | 107.0 |
| 50* | 12.6 | 118.5 | 131.1 |
| 52* | 36.9 | 101.8 | 138.7 |
- Discordant between 50% below cutoff and cutoff concentration (50 - 99.9 ng/mL) ** Discordant between cutoff and 50% above cutoff concentration (100 - 149.9 ng/mL)
Cross-reactivity: 100 ng/mL Cutoff
The cross-reactivity of various potentially interfering drugs were tested by spiking various concentrations of each substance into a pool of negative human urine and then evaluated against the assay's calibration curve in both qualitative and semi-quantitative modes. All samples were tested in duplicates.
The table below lists the concentration of each test compound that gave a response approximately equivalent to that of the cutoff calibrator (as positive) or the maximal concentration of the compound tested that gave a response below the response of the cutoff calibrator (as negative). Compounds tested at high concentration (100,000 ng/mL) with results below the cutoff value were listed as Not Detected (ND). Compounds tested below the high concentration (100,000 ng/mL) that gave a result below the cutoff value were given a "< %" value.
{9}------------------------------------------------
Oxycodone and Major Metabolites:
| Compound | TestConcentration(ng/mL) | % Cross-reactivity |
|---|---|---|
| Oxycodone | 100 | 100.00 % |
| Oxymorphone | 100 | 100.00 % |
| Noroxycodone | 25,000 | 0.40 % |
| Noroxymorphone | 60,000 | 0.17 % |
Structurally Related Compounds:
| Compound | TestConcentration(ng/mL) | % Cross-reactivity |
|---|---|---|
| 6-Acetylmorphine | 100,000 | ND |
| Buprenorphine | 100,000 | ND |
| Codeine | 100,000 | ND |
| Codeine-6ß-D-Glucuronide | 100,000 | ND |
| Dextromethorphan | 100,000 | ND |
| Dihydrocodeine | 100,000 | ND |
| Hydrocodone | 25,000 | 0.40 % |
| Hydromorphone | 25,000 | 0.40 % |
| Levorphanol | 100,000 | ND |
| Morphine | 100,000 | ND |
| Morphine-3ß-D-Glucuronide | 100,000 | ND |
| Morphine-6ß-D-Glucuronide | 100,000 | ND |
| Naloxone | 100,000 | ND |
| Naloxone-3B-D-Glucuronide | 100,000 | ND |
| Norbuprenorphine | 100,000 | ND |
| Norcodeine | 100,000 | ND |
| Norhydrocodone | 100,000 | ND |
| Oxymorphone-3B-D-Glucuronide | 230 | 43.48 % |
Structurally unrelated compounds were additionally spiked into pooled negative human urine to desired concentrations (as described below). These solutions were then split into three portions; one without oxycodone, and the remaining two that were further spiked with oxycodone standards to a final oxycodone concentration of 75 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively). Samples were then evaluated against the cutoff calibrator in qualitative mode or the assay's calibration curve in semi-quantitative mode. All samples were tested in duplicates. Compounds tested at high concentration (100,000 ng/mL) with results below the cutoff value were listed as Not Detected (ND). Compounds tested below the high concentration (100,000 ng/mL) that gave a result below the cutoff value were given a "< %" value.
{10}------------------------------------------------
| Compound | TestConcentration(ng/mL) | -25 % Oxycodone Cutoff(75 ng/mL)Result | +25 % Oxycodone Cutoff(125 ng/mL)Result |
|---|---|---|---|
| Acetaminophen | 100,000 | Neg | Pos |
| Acetylsalicylic Acid | 100,000 | Neg | Pos |
| Amitriptyline | 100,000 | Neg | Pos |
| Amlodipine Besylate | 100,000 | Neg | Pos |
| Amoxicillin | 100,000 | Neg | Pos |
| d-Amphetamine | 100,000 | Neg | Pos |
| Atorvastatin | 20,000 | Neg | Pos |
| Benzoylecgonine | 100,000 | Neg | Pos |
| Bupropion | 100,000 | Neg | Pos |
| Caffeine | 100,000 | Neg | Pos |
| Carbamazepine | 100,000 | Neg | Pos |
| Cetirizine | 100,000 | Neg | Pos |
| Chlorpheniramine | 100,000 | Neg | Pos |
| Chlorpromazine | 100,000 | Neg | Pos |
| Clomipramine | 100,000 | Neg | Pos |
| Desipramine | 100,000 | Neg | Pos |
| Diphenhydramine | 100,000 | Neg | Pos |
| Duloxetine | 100,000 | Neg | Pos |
| Fentanyl | 100,000 | Neg | Pos |
| Fluoxetine | 100,000 | Neg | Pos |
| Fluphenazine | 100,000 | Neg | Pos |
| Gabapentin | 100,000 | Neg | Pos |
| Ibuprofen | 100,000 | Neg | Pos |
| Imipramine | 100,000 | Neg | Pos |
| Lisinopril | 100,000 | Neg | Pos |
| Losartan | 10,000 | Neg | Pos |
| Loratadine | 100,000 | Neg | Pos |
| MDA (3,4-methylenedioxyamphetamine) | 100,000 | Neg | Pos |
| MDEA | 100,000 | Neg | Pos |
| MDMA (3,4-methylenedioxymethamphetamine) | 100,000 | Neg | Pos |
| Meperidine | 100,000 | Neg | Pos |
| Metformin | 100,000 | Neg | Pos |
| Metoprolol | 100,000 | Neg | Pos |
| Methadone | 100,000 | Neg | Pos |
| d-Methamphetamine | 100,000 | Neg | Pos |
| Nicotine | 100,000 | Neg | Pos |
| Nortriptyline | 100,000 | Neg | Pos |
| Omeprazole | 100,000 | Neg | Pos |
| Oxazepam | 100,000 | Neg | Pos |
| Phenobarbital | 100,000 | Neg | Pos |
| (1S,2S)-(+)Pseudoephedrine | 100,000 | Neg | Pos |
| Compound | TestConcentration(ng/mL) | -25 % Oxycodone Cutoff(75 ng/mL)Result | +25 % Oxycodone Cutoff(125 ng/mL)Result |
| Ranitidine | 100,000 | Neg | Pos |
| Salbutamol (Albuterol) | 100,000 | Neg | Pos |
| Sertraline | 100,000 | Neg | Pos |
| THC-COOH(11-Nor-Delta-9-THC-9-carboxylic acid) | 1000 | Neg | Pos |
| l -Thyroxine | 10,000 | Neg | Pos |
| Tramadol | 100,000 | Neg | Pos |
| Zolpidem | 10,000 | Neg | Pos |
Structurally Unrelated Pharmacological Compounds: 100 ng/mL Cutoff
{11}------------------------------------------------
Endogenous and Preservative Compound Interference: 100 ng/mL Cutoff
Endogenous and Preservative compounds were spiked into pooled negative human urine to desired concentrations. These solutions were then split into three portions; one without oxycodone, and the remaining two that were further spiked with oxycodone standards to a final oxycodone concentration of 75 ng/mL or 125 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively). Samples were then evaluated against the cutoff calibrator in qualitative mode and the assay's calibration curve in semi-quantitative mode. All samples were tested in duplicates.
| Interfering Substance | Concentrationof Compound(mg/dL) | -25 % Oxycodone Cutoff(75 ng/mL) | +25 % Oxycodone Cutoff(125 ng/mL) |
|---|---|---|---|
| Acetone | 1000 | Neg | Pos |
| Ascorbic Acid | 1500 | Neg | Pos |
| Bilirubin | 2 | Neg | Pos |
| Boric Acid | 1000 | Neg | Neg |
| Calcium Chloride (CaCl2) | 300 | Neg | Pos |
| Citric Acid (pH 3) | 800 | Neg | Pos |
| Creatinine | 500 | Neg | Pos |
| Ethanol | 1000 | Neg | Pos |
| Galactose | 10 | Neg | Pos |
| y-Globulin | 500 | Neg | Pos |
| Glucose | 3000 | Neg | Pos |
| Hemoglobin | 300 | Neg | Pos |
| β-hydroxybutyric Acid | 100 | Neg | Pos |
| Human Serum Albumin | 500 | Neg | Pos |
| Oxalic Acid | 100 | Neg | Pos |
| Potassium Chloride | 6000 | Neg | Pos |
| Riboflavin | 7.5 | Neg | Pos |
| Urea | 6000 | Neg | Pos |
| Uric Acid | 10 | Neg | Pos |
| Sodium Azide | 1000 | Neg | Pos |
| Sodium Chloride | 6000 | Neg | Pos |
| Sodium Fluoride | 1000 | Neg | Pos |
| Sodium Phosphate | 300 | Neg | Pos |
{12}------------------------------------------------
The following endogenous and preservative compounds which showed interference at ±25 % of the cutoff concentration were then spiked into negative urine and at ±50 % of the cutoff concentration (50 ng/mL and 150 ng/mL) for the assay.
Interference was observed with Boric Acid at 1 % w/v. No other significant undesired crossreactants or endogenous/preservative substance interference were observed.
| Interfering Substance | Concentrationof Compound(mg/dL) | -50 % Oxycodone Cutoff(50 ng/mL) | +50 % Oxycodone Cutoff(150 ng/mL) |
|---|---|---|---|
| Boric Acid | 1000 | Neg | Neg |
Specific Gravity Interference: 100 ng/mL Cutoff
Samples ranging in specific gravity from 1.000 to 1.030 were spiked to a final oxycodone concentration of either 75 ng/mL or 125 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration. respectively). These samples were then evaluated in both semi-quantitative and qualitative modes. There were no deviations from the expected positive or negative results.
pH Interference: 100 ng/mL Cutoff
Negative urine and urine spiked with oxycodone to a final oxycodone concentration of either 75 ng/mL or 125 ng/mL (as negative or positive controls. ±25 % of the cutoff concentration. respectively) were adjusted to pH levels from 3 to 11 and tested by the assay. The pH adjusted solutions were evaluated in both qualitative and semi-quantitative modes and there were no deviations from the expected results.
Precision: 300 ng/mL Cutoff
The assay was tested in qualitative and semi-quantitative mode by spiking oxycodone into pooled negative urine at concentrations ±25 %, ±50 %, ±75 %, and ±100 % of the cutoff concentration.
Results shown below were obtained by testing all samples in replicate of two runs a day for 22 days on one Beckman Coulter AU480 automatic clinical analyzer for a total of 88 runs.
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| OxycodoneConcentration | % of Cutoff | Number ofDetermination | ImmunoassayResult | Number ofDetermination | ImmunoassayResult |
| 0 ng/mL | 0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 25 % | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | 50 % | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | 75 % | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100 % | 22 | 6 Neg/16 Pos | 88 | 27 Neg/61 Pos |
| 375 ng/mL | 125 % | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | 150 % | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | 175 % | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | 200 % | 22 | 22 Positive | 88 | 88 Positive |
Semi-Ouantitative Positive/Negative Results:
Qualitative Positive/Negative Results:
{13}------------------------------------------------
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| OxycodoneConcentration | % of Cutoff | Number ofDeterminations | ImmunoassayResult | Number ofDeterminations | ImmunoassayResult |
| 0 ng/mL | 0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 25 % | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | 50 % | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | 75 % | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100 % | 22 | 10 Neg / 12 Pos | 88 | 40 Neg / 48 Pos |
| 375 ng/mL | 125 % | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | 150 % | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | 175 % | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | 200 % | 22 | 22 Positive | 88 | 88 Positive |
Analytical Recovery: 300 ng/mL Cutoff
To demonstrate recovery of the entire assay range, a drug free-urine pool spiked with oxycodone at 800 ng/mL was serially diluted. Each sample was run in 10 replicates and the average was used to determine percent recovery compared to the expected target value. Results are summarized below.
| TargetConcentration(ng/mL) | DeterminedConcentration Range(ng/mL) | DeterminedConcentration Average(ng/mL) | Average% Recovery |
|---|---|---|---|
| 800 | 829.6 - 859.3 | 843.5 | 105.4 % |
| 720 | 769.7 - 794.1 | 784.2 | 108.9 % |
| 640 | 689.6 - 731.2 | 712.8 | 111.4 % |
| 560 | 603.8 - 640.0 | 624.3 | 111.5 % |
| 480 | 497.8 - 525.2 | 514.2 | 107.1 % |
| 400 | 427.2 - 451.5 | 436.8 | 109.2 % |
| 320 | 327.6 - 359.1 | 345.0 | 107.8 % |
| 240 | 242.9 - 260.8 | 250.8 | 104.5 % |
| 160 | 168.3 - 183.4 | 173.9 | 108.7 % |
| 80 | 82.9 - 95.0 | 89.0 | 111.2 % |
| 0 | -5.2 - 5.9 | 0.3 | N/A |
Method Comparison - Clinical Samples: 300 ng/mL Cutoff
A total of ninety (90) unaltered clinical samples were tested with the LZI Oxycodone III Enzyme Immunoassay on the Beckman Coulter AU480 automated clinical analyzer. All samples were tested in singlet.
All samples were confirmed with LC/MS for oxycodone and oxymorphone concentrations.
{14}------------------------------------------------
Semi-Quantitative Results:
| OxycodoneResults300 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby LC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50% above thecutoffconcentration) | High Positive(Greater than50 % abovethe cutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 2* | 11 | 33 | 97.8 % |
| Negative | 20 | 6 | 17 | 1** | 0 | 95.6 % |
Discordant samples determined when comparing LC/MS oxycodone and oxymorphone results with EIA results on the Beckman Coulter AU480 automated clinical analyser are shown in the table below.
| Sample# | LC/MSOxycodone(ng/mL) | LC/MSOxymorphone(ng/mL) | TotalOxycodone +OxymorphoneLC/MS(ng/mL) |
|---|---|---|---|
| 42* | 200.2 | 49.5 | 249.7 |
| 43* | 53.0 | 203.5 | 256.5 |
| 55** | 46.7 | 367.3 | 414.0 |
- Discordant between 50 % below cutoff and cutoff concentration (150 - 299.9 ng/mL)
** Discordant between cutoff and 50 % above cutoff concentration (300 - 449.9 ng/mL)
Qualitative Accuracy Study:
| OxycodoneResults300 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby LC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50% above thecutoffconcentration) | High Positive(Greater than50 % abovethe cutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 2* | 10 | 33 | 95.6 % |
| Negative | 20 | 6 | 17 | 2** | 0 | 95.6 % |
Discordant samples determined when comparing LC/MS oxycodone and oxymorphone results with EIA results on the Beckman Coulter AU480 automated clinical analyser are shown in the table below.
| Sample# | LC/MSOxycodone(ng/mL) | LC/MSOxymorphone(ng/mL) | TotalOxycodone +OxymorphoneLC/MS(ng/mL) |
|---|---|---|---|
| 42* | 200.2 | 49.5 | 249.7 |
| 43* | 53.0 | 203.5 | 256.5 |
| 50** | 177.2 | 212.1 | 389.3 |
| 55** | 46.7 | 367.3 | 414.0 |
- Discordant between 50% below cutoff and cutoff concentration (150 - 299.9 ng/mL)
** Discordant between cutoff and 50% above cutoff concentration (300 - 449.9 ng/mL)
{15}------------------------------------------------
Cross-reactivity: 300 ng/mL Cutoff
The cross-reactivity of various potentially interfering drugs were tested by spiking various concentrations of each substance into a pool of negative human urine and then evaluated against the assay's calibration curve in both qualitative and semi-quantitative modes. All samples were tested in duplicates.
The table below lists the concentration of each test compound that gave a response approximately equivalent to that of the cutoff calibrator (as positive) or the maximal concentration of the compound tested that gave a response below the response of the cutoff calibrator (as negative). Compounds tested at high concentration (100,000 ng/mL) with results below the cutoff value were listed as Not Detected (ND). Compounds tested below the high concentration (100,000 ng/mL) that gave a result below the cutoff value were given a "< %" value.
Oxycodone and Major Metabolites:
| Compound | TestConcentration(ng/mL) | % Cross-reactivity |
|---|---|---|
| Oxycodone | 300 | 100.00 % |
| Oxymorphone | 300 | 100.00 % |
| Noroxycodone | 75,000 | 0.40 % |
| Noroxymorphone | 100,000 | ND |
Structurally Related Compounds:
| Compound | TestConcentration(ng/mL) | % Cross-reactivity |
|---|---|---|
| 6-Acetylmorphine | 100,000 | ND |
| Buprenorphine | 100,000 | ND |
| Codeine | 100,000 | ND |
| Codeine-6β-D-Glucuronide | 100,000 | ND |
| Dextromethorphan | 100,000 | ND |
| Dihydrocodeine | 100,000 | ND |
| Hydrocodone | 75,000 | 0.40 % |
| Hydromorphone | 75,000 | 0.40 % |
| Levorphanol | 100,000 | ND |
| Morphine | 100,000 | ND |
| Morphine-3β-D-Glucuronide | 100,000 | ND |
| Morphine-6β-D-Glucuronide | 100,000 | ND |
| Naloxone | 100,000 | ND |
| Naloxone-3β-D-Glucuronide | 100,000 | ND |
| Norbuprenorphine | 100,000 | ND |
| Norcodeine | 100,000 | ND |
| Norhydrocodone | 100,000 | ND |
| Oxymorphone-3β-D-Glucuronide | 700 | 42.86 % |
{16}------------------------------------------------
Structurally unrelated compounds were additionally spiked into pooled negative human urine to desired concentrations (as described below). These solutions were then split into three portions; one without oxycodone, and the remaining two that were further spiked with oxycodone standards to a final oxycodone concentration of 225 ng/mL or 375 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively). Samples were then evaluated against the cutoff calibrator in qualitative mode and against the assay's calibration curve in semiquantitative mode. All samples were tested in duplicates. Compounds tested at high concentration (100,000 ng/mL) with results below the cutoff value were listed as Not Detected (ND). Compounds tested below the high concentration (100,000 ng/mL) that gave a result below the cutoff value were given a "< %" value.
| Compound | TestConcentration(ng/mL) | -25 % Oxycodone Cutoff(225 ng/mL)Result | +25 % Oxycodone Cutoff(375 ng/mL)Result |
|---|---|---|---|
| Acetaminophen | 100,000 | Neg | Pos |
| Acetylsalicylic Acid | 100,000 | Neg | Pos |
| Amitriptyline | 100,000 | Neg | Pos |
| Amlodipine Besylate | 100,000 | Neg | Pos |
| Amoxicillin | 100,000 | Neg | Pos |
| d-Amphetamine | 100,000 | Neg | Pos |
| Atorvastatin | 20,000 | Neg | Pos |
| Benzoylecgonine | 100,000 | Neg | Pos |
| Bupropion | 100,000 | Neg | Pos |
| Caffeine | 100,000 | Neg | Pos |
| Carbamazepine | 100,000 | Neg | Pos |
| Cetirizine | 100,000 | Neg | Pos |
| Chlorpheniramine | 100,000 | Neg | Pos |
| Chlorpromazine | 100,000 | Neg | Pos |
| Clomipramine | 100,000 | Neg | Pos |
| Desipramine | 100,000 | Neg | Pos |
| Diphenhydramine | 100,000 | Neg | Pos |
| Duloxetine | 100,000 | Neg | Pos |
| Fentanyl | 100,000 | Neg | Pos |
| Fluoxetine | 100,000 | Neg | Pos |
| Fluphenazine | 100,000 | Neg | Pos |
| Gabapentin | 100,000 | Neg | Pos |
| Ibuprofen | 100,000 | Neg | Pos |
| Imipramine | 100,000 | Neg | Pos |
| Lisinopril | 100,000 | Neg | Pos |
| Losartan | 10,000 | Neg | Pos |
| Loratadine | 100,000 | Neg | Pos |
| MDA (3,4-methylenedioxyamphetamine) | 100,000 | Neg | Pos |
| MDEA | 100,000 | Neg | Pos |
| MDMA (3,4-methylenedioxymethamphetamine) | 100,000 | Neg | Pos |
| Meperidine | 100,000 | Neg | Pos |
Structurally Unrelated Pharmacological Compounds: 300 ng/mL Cutoff
{17}------------------------------------------------
| Compound | TestConcentration(ng/mL) | -25 % Oxycodone Cutoff(225 ng/mL)Result | +25 % Oxycodone Cutoff(375 ng/mL)Result |
|---|---|---|---|
| Metformin | 100,000 | Neg | Pos |
| Metoprolol | 100,000 | Neg | Pos |
| Methadone | 100,000 | Neg | Pos |
| d-Methamphetamine | 100,000 | Neg | Pos |
| Nicotine | 100,000 | Neg | Pos |
| Nortriptyline | 100,000 | Neg | Pos |
| Omeprazole | 100,000 | Neg | Pos |
| Oxazepam | 100,000 | Neg | Pos |
| Phenobarbital | 100,000 | Neg | Pos |
| (1S,2S)-(+)Pseudoephedrine | 100,000 | Neg | Pos |
| Quetiapine | 100,000 | Neg | Pos |
| Ranitidine | 100,000 | Neg | Pos |
| Salbutamol (Albuterol) | 100,000 | Neg | Pos |
| Sertraline | 100,000 | Neg | Pos |
| THC-COOH(11-Nor-Delta-9-THC-9-carboxylic acid) | 1000 | Neg | Pos |
| l-Thyroxine | 10,000 | Neg | Pos |
| Tramadol | 100,000 | Neg | Pos |
| Zolpidem | 10,000 | Neg | Pos |
Endogenous and Preservative Compound Interference: 300 ng/mL Cutoff
Endogenous and Preservative compounds were spiked into pooled negative human urine to desired concentrations. These solutions were then split into three portions; one without ox ycodone, and the remaining two that were further spiked with oxycodone standards to a final oxycodone concentration of 225 ng/mL or 375 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively). Samples were then evaluated against the cutoff calibration in qualitative mode and against the assay's calibration curve in semi-quantitative mode. All samples were tested in duplicates.
| Interfering Substance | Concentrationof Compound(mg/dL) | -25 % Oxycodone Cutoff(225 ng/mL) | +25 % Oxycodone Cutoff(375 ng/mL) |
|---|---|---|---|
| Acetone | 1000 | Neg | Pos |
| Ascorbic Acid | 1500 | Neg | Pos |
| Bilirubin | 2 | Neg | Pos |
| Boric Acid | 1000 | Neg | Neg |
| Calcium Chloride (CaCl2) | 300 | Neg | Pos |
| Citric Acid (pH 3) | 800 | Neg | Pos |
| Creatinine | 500 | Neg | Pos |
| Ethanol | 1000 | Neg | Pos |
| Galactose | 10 | Neg | Pos |
| y-Globulin | 500 | Neg | Pos |
| Glucose | 3000 | Neg | Pos |
| Hemoglobin | 300 | Neg | Pos |
| β-hydroxybutyric Acid | 100 | Neg | Pos |
{18}------------------------------------------------
| Interfering Substance | Concentrationof Compound(mg/dL) | -25 % Oxycodone Cutoff(225 ng/mL) | +25 % Oxycodone Cutoff(375 ng/mL) |
|---|---|---|---|
| Human Serum Albumin | 500 | Neg | Pos |
| Oxalic Acid | 100 | Neg | Pos |
| Potassium Chloride | 6000 | Neg | Pos |
| Riboflavin | 7.5 | Neg | Pos |
| Urea | 6000 | Neg | Pos |
| Uric Acid | 10 | Neg | Pos |
| Sodium Azide | 1000 | Neg | Pos |
| Sodium Chloride | 6000 | Neg | Pos |
| Sodium Fluoride | 1000 | Neg | Pos |
| Sodium Phosphate | 300 | Neg | Pos |
The following endogenous and preservative compounds which showed interference at ±25 % of the cutoff concentrations were then spiked into negative urine and at ±50 % of the cutoff concentration (150 ng/mL and 450 ng/mL) for the assay.
No other significant undesired cross-reactants or endogenous/preservative substance interference were observed.
| Interfering Substance | Concentrationof Compound(mg/dL) | -50 % Oxycodone Cutoff(150 ng/mL) | +50 % Oxycodone Cutoff(450 ng/mL) |
|---|---|---|---|
| Boric Acid | 1000 | Neg | Pos |
Specific Gravity Interference: 300 ng/mL Cutoff
Samples ranging in specific gravity from 1.000 to 1.030 were spiked to a final oxycodone concentration of either 225 ng/mL or 375 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively). These samples were then evaluated in both semi-quantitative and qualitative modes. There were no deviations from the expected positive or negative results.
pH Interference: 300 ng/mL Cutoff
Negative urine and urine spiked with oxycodone to a final oxycodone concentration of either 225 ng/mL or 375 ng/mL (as negative or positive controls, ±25 % of the cutoff concentration, respectively) were adjusted to pH levels from 3 to 11 levels and tested by the assay. The pH adjusted solutions were evaluated in both qualitative and semi-quantitative modes and there were no deviations from the expected results.
Conclusions:
The information provided in this pre-market notification demonstrates that the LZI Oxycodone III Enzyme Immunoassay is substantially equivalent to the legally marketed predicate device for its intended use, as demonstrated through comparison of intended use and performance characteristics.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).