(434 days)
The Psychemedics homogeneous enzyme immunoassay (HEIA) for opiates in hair is an enzyme immunoassay for the preliminary qualitative detection of opiates in human head and body hair using a morphine calibrator at 2 ng morphine/10 mg hair for the purpose of identifying opiate use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for opiates in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/ MS/MS) is the preferred confirmatory method.
The Psychemedics homogeneous enzyme immunoassay (HEIA) for oxycodone in hair is an enzyme immunoassay for the preliminary qualitative detection of oxycodone in human head and body hair using an oxycodone calibrator at 2 ng oxycodone/10 mg hair for the purpose of identifying opioid use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for oxycodone in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) is the preferred confirmatory method.
The homogeneous enzyme immunoassay (HEIA) test consists of two parts; a pre-analytical hair treatment procedure (to extract opioids from the solid hair matrix to form a measurable liquid matrix) and the screening assay, the Psychemedics Opiates HEIA and the Psychemedics Oxycodone HEIA. The screening portion of the test system is based on competition for antibody binding sites between drug in the measurable liquid matrix and drug-labeled recombinant glucose-6-phosphate dehydrogenase (G6PDH). As the antibody binds labeled G6PDH, enzyme activity decreases. In the presence of drug, enzyme activity increases in direct proportion to the drug concentration. Active enzyme reduces nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically.
The Psychemedics Opiates HEIA consists of reagents R1 (anti-opiates monoclonal antibody with substrate) and R2 (morphine labeled recombinant G6PDH). The Psychemedics Oxycodone HEIA consists of reagents R1 (anti-oxycodone monoclonal antibody with substrate) and R2 (oxycodone labeled recombinant G6PDH).
Below you will find the acceptance criteria and study details for the Psychemedics Homogeneous Enzyme Immunoassay (HEIA) for Opiates and Oxycodone in Hair:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly demonstrated by the performance studies showing the device's ability to accurately classify samples as positive or negative compared to LC/MS/MS confirmation, especially at and around the cut-off concentrations. The stated goal for both assays is to provide a "preliminary qualitative detection" of opiates or oxycodone.
The performance is reported in terms of precision (intra-assay and inter-assay), cross-reactivity, and comparison studies against LC/MS/MS.
General Acceptance Criteria (Implied by the study results presented):
- Precision: The assay should reliably produce consistent results for samples at various concentrations around the cutoff, indicating good repeatability and reproducibility. The reported data shows 100% agreement (either all negative or all positive) for samples at different concentrations relative to the cutoff for both intra-assay and inter-assay precision.
- Specificity (Cross-reactivity): The assay should primarily detect the target analytes (opiates or oxycodone) and have minimal cross-reactivity with other structurally similar compounds or common substances. The cross-reactivity tables indicate which compounds show cross-reactivity and at what concentrations. Compounds showing no cross-reactivity are also listed.
- Interference: The assay should not be significantly impacted by common interfering substances, including cosmetic treatments. The study reports no interference from numerous compounds, and also notes which compounds show interference (e.g., imipramine in the oxycodone assay). Cosmetic treatments also did not alter the results for both positive and negative samples.
- Agreement with Confirmatory Method (LC/MS/MS): The preliminary qualitative results should show reasonable agreement with the definitive LC/MS/MS confirmatory method, especially highlighting how the assay performs around the critical cutoff concentration.
| Acceptance Criteria (Implied) | Reported Device Performance (Psychemedics Opiates HEIA) | Reported Device Performance (Psychemedics Oxycodone HEIA) |
|---|---|---|
| Precision | Intra-Assay & Inter-Assay: | Intra-Assay & Inter-Assay: |
| - Reliability/Reproducibility | At concentrations: | At concentrations: |
| -100%, -75%, -50%, -25% of cutoff: All Negative (8/8 for intra-assay, 80/80 for inter-assay) | -100%, -75%, -50%, -25% of cutoff: All Negative (8/8 for intra-assay, 80/80 for inter-assay) | |
| +25%, +50%, +75%, +100% of cutoff: All Positive (8/8 for intra-assay, 80/80 for inter-assay) | +25%, +50%, +75%, +100% of cutoff: All Positive (8/8 for intra-assay, 80/80 for inter-assay) | |
| Specificity | Cross-Reactivity: Codeine (100%), 6-Acetylmorphine (80%), Hydrocodone (20%), Hydromorphone (13%), Buprenorphine (10%). Oxycodone, Oxymorphone (<2%). Numerous other compounds showed no cross-reactivity. | Cross-Reactivity: Hydrocodone (80%), Codeine (67%), 6-Acetylmorphine (27%), Morphine (27%), Buprenorphine (13%), Hydromorphone (10%), Oxymorphone (5%), Imipramine (2%). Numerous other compounds showed no cross-reactivity. |
| Interference | Chemical Interference: Numerous compounds shown to have no interference. Cosmetic Treatments: 15 opiate-negative and 10 opiate-positive head hair samples treated with perm, dye, shampoo, and relaxer remained negative/positive, respectively. | Chemical Interference: Numerous compounds shown to have no interference, exception: Imipramine (inhibitor at ≥ 100 ng imipramine/10 mg hair). Cosmetic Treatments: 15 opioid-negative and 10 opioid-positive head hair samples treated with perm, dye, shampoo, and relaxer remained negative/positive, respectively. |
| Agreement with LC/MS/MS | Opiates HEIA vs. LC/MS/MS (230 samples): | Oxycodone HEIA vs. LC/MS/MS (219 samples): |
| - Qualitative detection | HEIA Positive Samples: | HEIA Positive Samples: |
| - LC/MS/MS <1.0 ng/10mg: 43 samples (i.e., these were false positives by HEIA or cross-reactivity with other substances at sub-cutoff levels). The document states discordant results were due to codeine, 6-AM, and morphine detected by LC-MS/MS, even if below the specific threshold for confirmation, implying the HEIA is sensitive to these broader opiate markers. | - LC/MS/MS <1.0 ng/10mg: 48 samples (similar interpretation as opiates, with discordant results noted as hydrocodone detection by LC-MS/MS contributing to HEIA positive results). | |
| - LC/MS/MS 1.0-1.99 ng/10mg: 3 samples | - LC/MS/MS 1.0-1.99 ng/10mg: 8 samples | |
| - LC/MS/MS 2.0-3.0 ng/10mg: 14 samples | - LC/MS/MS 2.0-3.0 ng/10mg: 15 samples | |
| - LC/MS/MS >3.0 ng/10mg: 42 samples (strong agreement for high concentrations) | - LC/MS/MS >3.0 ng/10mg: 31 samples (strong agreement for high concentrations) | |
| HEIA Negative Samples: | HEIA Negative Samples: | |
| - LC/MS/MS <1.0 ng/10mg: 118 samples (strong agreement for true negatives) | - LC/MS/MS <1.0 ng/10mg: 103 samples (strong agreement for true negatives) | |
| - LC/MS/MS 1.0-1.99 ng/10mg: 10 samples (false negatives by HEIA when LC/MS/MS was near cutoff) | - LC/MS/MS 1.0-1.99 ng/10mg: 14 samples (false negatives by HEIA when LC/MS/MS was near cutoff) | |
| - LC/MS/MS 2.0-3.0 ng/10mg: 0 samples (no false negatives above cutoff) | - LC/MS/MS 2.0-3.0 ng/10mg: 0 samples (no false negatives above cutoff) | |
| - LC/MS/MS >3.0 ng/10mg: 0 samples (no false negatives at higher concentrations) | - LC/MS/MS >3.0 ng/10mg: 0 samples (no false negatives at higher concentrations) |
Since this is an in vitro diagnostic device for preliminary qualitative detection, the performance metrics (precision, cross-reactivity, and reasonable agreement with a confirmatory method) are the key indicators of acceptance. The device is not intended to be a standalone definitive diagnostic.
Study Details:
-
Sample sizes used for the test set and the data provenance:
- Psychemedics Opiates HEIA: 230 individual hair samples.
- Psychemedics Oxycodone HEIA: 219 individual hair samples.
- Data Provenance: Samples were "collected anonymously from a workplace setting." The document does not specify the country of origin, but given the FDA submission, it's likely primarily U.S. based. The data appears retrospective, as stated "The stored hair samples were then tested..."
- Precision Studies: Intra-assay precision involved 8 measurements per concentration level, and inter-assay precision involved 80 measurements per concentration level. These were achieved by spiking negative hair with validated calibrator and control solutions.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- No human experts were used for establishing ground truth. The devices being reviewed are in vitro diagnostic devices, which perform quantitative/qualitative analysis.
- The ground truth was established by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS), which is described as the "preferred confirmatory method" and is a highly sensitive and specific analytical technique for drug detection. This is a chemical/analytical ground truth, not an expert-driven one.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- No human adjudication method was used. The comparison was directly between the test device's preliminary result and the LC/MS/MS confirmatory result.
-
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:
- No MRMC or human-in-the-loop study was performed. This is an immunoassay, not an AI-assisted diagnostic. Its purpose is to provide a screening result, not to assist human interpretation of complex medical images or data.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies described are standalone performance evaluations of the immunoassay itself. The device is an automated chemical analyzer.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The type of ground truth used was analytical confirmation by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS). For in vitro diagnostic assays measuring chemical substances, this is the gold standard for ground truth.
-
The sample size for the training set:
- This document describes a 510(k) submission, which typically focuses on demonstrating substantial equivalence through performance testing, not on developing a machine learning model. Therefore, a separate "training set" in the context of AI/ML is not applicable here. The samples used for performance evaluation (230 for Opiates HEIA, 219 for Oxycodone HEIA) are test samples for validation, not a training set. The calibrators and control solutions used in precision studies would be analogous to internal "training" or calibration materials for the assay's function, but not in the sense of a dataset for model training.
-
How the ground truth for the training set was established:
- As noted above, there isn't a "training set" in the AI/ML context. For the assay's internal calibration and control (which could be considered analogous), the document states: "Psychemedics prepares calibrators and control materials using drug stocks purchased from a commercial vendor. Each lot of drug is received with its specific certificate of analysis. The commercially obtained stock is made into calibrators and controls to the desired concentrations. The concentrations are confirmed by LC/MS/MS." This indicates that the ground truth for the calibrators and controls is also established by LC/MS/MS.
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July 27, 2021
Psychemedics Corporation Neil Stowe Principal Scientist 5832 Uplander Way Culver City, California 90230
Re: K201326
Trade/Device Name: Psychemedics Homogeneous Enzyme Immunoassay for Opiates in Hair, Psychemedics Homogeneous Enzyme Immunoassay for Oxycodone in Hair Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: DJG Dated: January 5, 2021 Received: January 6, 2021
Dear Neil Stowe:
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.
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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) 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 (QS) 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 medical devices and radiation-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. 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) K201326
Device Name
Psychemedics Homogeneous Enzyme Immunoassay for Opiates in Hair Psychemedics Homogeneous Enzyme Immunoassay for Oxycodone in Hair
Indications for Use (Describe)
The Psychemedics homogeneous enzyme immunoassay (HEIA) for opiates in hair is an enzyme immunoassay for the preliminary qualitative detection of opiates in human head and body hair using a morphine calibrator at 2 ng morphine/10 mg hair for the purpose of identifying opiate use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for opiates in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/ MS/MS) is the preferred confirmatory method.
The Psychemedics homogeneous enzyme immunoassay (HEIA) for oxycodone in hair is an enzyme immunoassay for the preliminary qualitative detection of oxycodone in human head and body hair using an oxycodone calibrator at 2 ng oxycodone/10 mg hair for the purpose of identifying opioid use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for oxycodone in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) is the preferred confirmatory method.
| 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
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.
The assigned 510(k) number is: K201326
| Submitted By: | Psychemedics Corporation |
|---|---|
| 5832 Uplander Way | |
| Culver City, CA 90230 | |
| TEL: 310 216 7776 | |
| FAX: 310 216 6662 | |
| Submission Contact: | Neil Stowe |
| Date Prepared: | July 26, 2021 |
| Device Trade Name: | Psychemedics Homogeneous Enzyme Immunoassay for Opiates inHairPsychemedics Homogeneous Enzyme Immunoassay for Oxycodonein Hair |
| Predicate Device: | Psychemedics Microplate EIA for Opiates in Hair, K111926 andPsychemedics Microplate EIA for Oxycodone in Hair, K123799 |
| Product Code: | DJG |
| Device/ClassificationName: | 21 CFR 862.3650 Opiate Test System, Classification II |
| Intended Use: | The Psychemedics homogeneous enzyme immunoassay (HEIA) foropiates in hair is an enzyme immunoassay for the preliminaryqualitative detection of opiates in human head and body hair using amorphine calibrator at 2 ng morphine/10m mg hair for the purpose ofidentifying opiate use. This is an in vitro diagnostic device intendedexclusively for Psychemedics use only and is not intended for sale toanyone. The Psychemedics homogeneous enzyme immunoassayprovides only a preliminary analytical test result. A more specificalternative chemical method must be used in order to obtain aconfirmed analytical result. Liquid Chromatography/Mass |
| Spectrometry/Mass Spectrometry (LC/MS/MS) is the preferredconfirmatory method. | |
| The Psychemedics homogeneous enzyme immunoassay (HEIA) foroxycodone in hair is an enzyme immunoassay for the preliminaryqualitative detection of oxycodone in human head and body hairusing an oxycodone calibrator at 2 ng oxycodone/10 mg hair for thepurpose of identifying opioid use. This is an in vitro diagnosticdevice intended exclusively for Psychemedics use only and is notintended for sale to anyone. The Psychemedics homogeneousenzyme immunoassay provides only a preliminary analytical testresult. A more specific alternative chemical method must be used inorder to obtain a confirmed analytical result. LiquidChromatography/Mass Spectrometry/Mass Spectrometry(LC/MS/MS) is the preferred confirmatory method. | |
| Device Description: | The homogeneous enzyme immunoassay (HEIA) test consists oftwo parts; a pre-analytical hair treatment procedure (to extractopioids from the solid hair matrix to form a measurable liquidmatrix) and the screening assay, the Psychemedics Opiates HEIAand the Psychemedics Oxycodone HEIA. The screening portion ofthe test system is based on competition for antibody binding sitesbetween drug in the measurable liquid matrix and drug-labeledrecombinant glucose-6-phosphate dehydrogenase (G6PDH). As theantibody binds labeled G6PDH, enzyme activity decreases. In thepresence of drug, enzyme activity increases in direct proportion tothe drug concentration. Active enzyme reduces nicotinamideadenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measuredspectrophotometrically. |
| The Psychemedics Opiates HEIA consists of reagents R1 (anti-opiates monoclonal antibody with substrate) and R2 (morphinelabeled recombinant G6PDH). The Psychemedics OxycodoneHEIA consists of reagents R1 (anti-oxycodone monoclonalantibody with substrate) and R2 (oxycodone labeled recombinantG6PDH). | |
| Sample Collectionand Stability: | A sample of hair should be cut as close as possible to the skin. Thehair is placed in a V-shaped aluminum foil sample holder with theroot end of the hair protruding beyond the slanted edge of the foil. |
| The aluminum foil is crimped around the sample, securing the hairspecimen firmly into place within the foil. The hair sample, crimpedwithin the foil, is placed in a sample acquisition card envelope andthe envelope is sealed with a tamper-evident seal. Hair specimens arekept at ambient temperature in a secure location until they areshipped without refrigeration to the laboratory. Stability of opiates inhair samples stored at room temperature has been shown forapproximately 2 months. Opiates in samples shipped coast-to-coasttwice was stable. | |
| Materials Required: | Hair sample HEIA for Opiates, HEIA for Oxycodone, automatedclinical chemistry analyzer, LC/MS/MS for confirmation. |
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Comparison with Predicate:
| Device & PredicateDevice(s): | K201326 | K111926 |
|---|---|---|
| Device Trade Name | Psychemedics Homogeneous EnzymeImmunoassay for Opiates in Hair | Psychemedics MicroplateEIA for Opiates in Hair |
| General DeviceCharacteristicSimilarities | ||
| IntendedUse/Indications ForUse | The Psychemedics homogeneous enzymeimmunoassay (HEIA) for opiates is an enzymeimmunoassay for the preliminary qualitativedetection of opiates in human head and body hairusing a morphine calibrator at 2 ng morphine/10mg hair for the purpose of identifying opiate use.This is an in vitro diagnostic device intendedexclusively for Psychemedics use only and is notintended for sale to anyone. The Psychemedicshomogeneous enzyme immunoassay providesonly a preliminary analytical test result. A morespecific alternative chemical method must beused in order to obtain a confirmed analyticalresult. Liquid Chromatography/MassSpectrometry/Mass Spectrometry (LC/MS/MS) isthe preferred confirmatory method. | The Psychemedics MicroplateEIA for Opiates is an enzymeimmunoassay (EIA) for thepreliminary qualitativedetection of opiates in humanhead and body hair samplesusing a morphine calibrator at2 ng/10 mg hair cutoff for thepurpose of identifying opiateuse. |
| Sample Matrix | Human Hair | Same |
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| General DeviceCharacteristicDifferences | ||
|---|---|---|
| Method ofMeasurement | Automated Clinical ChemistryAnalyzer at 340 nm | Microplate Reader at 450 nm |
| Antibody | Mouse monoclonal | Rabbit polyclonal |
| Device & PredicateDevice(s): | K201326 | K123799 |
|---|---|---|
| Device Trade Name | Psychemedics Homogeneous EnzymeImmunoassay for Oxycodone in Hair | Psychemedics Microplate EIAfor Oxycodone in Hair |
| General DeviceCharacteristicSimilarities | ||
| IntendedUse/Indications ForUse | The Psychemedics homogeneous enzymeimmunoassay (HEIA) for oxycodone is anenzyme immunoassay for the preliminaryqualitative detection of oxycodone in humanhead and body hair using an oxycodonecalibrator at 2 ng oxycodone/10 mg hair for thepurpose of identifying opioid use. This is an invitro diagnostic device intended exclusively forPsychemedics use only and is not intended forsale to anyone. The Psychemedics homogeneousenzyme immunoassay provides only apreliminary analytical test result. A morespecific alternative chemical method must beused in order to obtain a confirmed analyticalresult. Liquid Chromatography/MassSpectrometry/Mass Spectrometry (LC/MS/MS)is the preferred confirmatory method. | The Psychemedics MicroplateEIA for Oxycodone is anenzyme immunoassay (EIA)for the preliminary qualitativedetection of oxycodone inhuman head and body hairsamples using an oxycodonecalibrator at 2 ng/10 mg haircutoff for the purpose ofidentifying oxycodone use. |
| Sample Matrix | Same | Human hair |
| General DeviceCharacteristicDifferences | ||
| Method ofMeasurement | Automated Clinical ChemistryAnalyzer at 340 nm | Microplate Reader at 450 nm |
| Antibody | Mouse monoclonal | Rabbit polyclonal |
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Performance Testing Summary:
Precision studies were performed by spiking negative hair with previously validated LC/MS/MS validated calibrator and control solutions to achieve concentrations of negative, the cutoff calibrator of 2 ng morphine/10 mg hair or 2 ng oxycodone/10 mg hair, and +/-75%, +/-50% and +/-25% of the cutoff calibrator. The results were identical for both immunoassays and are summarized below:
| Summary Intra-AssayPrecision | Summary Inter-AssayPrecision | ||||
|---|---|---|---|---|---|
| Level | NEG | POS | Level | NEG | POS |
| -100% | 8 | 0 | -100% | 80 | 0 |
| -75% | 8 | 0 | -75% | 80 | 0 |
| -50% | 8 | 0 | -50% | 80 | 0 |
| -25% | 8 | 0 | -25% | 80 | 0 |
| +25% | 0 | 8 | +25% | 0 | 80 |
| +50 | 0 | 8 | +50 | 0 | 80 |
| +75% | 0 | 8 | +75% | 0 | 80 |
| +100% | 0 | 8 | +100% | 0 | 80 |
Cross Reactivity
Summary:
The cross reactivity of the following metabolites and opiate structural analogs was evaluated by determining the minimum concentration that would result approximately equivalent to the 2.0 ng morphine/10 mg hair cutoff.
| Opiates HEIA: Cross Reactivities of Structurally RelatedCompounds and Metabolites | ||
|---|---|---|
| Compound | % CrossReactivity | ConcentrationEquivalent to2.0 ngMorphine/10 mg Hair |
| Codeine | 100 | 2.0 |
| 6-Acetylmorphine | 80 | 2.5 |
| Hydrocodone | 20 | 10 |
| Hydromorphone | 13 | 15 |
| Buprenorphine | 10 | 20 |
| Oxycodone | <2 | >100 |
| Oxymorphone | <2 | >100 |
The following compounds were shown to have no cross reactivity in the Opiates assay.
Lisinopril Dihydrate, Atropine, Bupropion, Cotinine, Cannabinol, Chlorpheniramine Maleate, O-Desmethylvenlafaxine, Desipramine, Doxylamine Succinate, 1S, 2R-Ephedrine, Amitriptyline, Dextromethorphan, Lidocaine, Methocarbamol, Nordoxepin,
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Pentazocine, Phenylephrine, Triamterene, Naproxen, Nicotine, Nortriptyline, Propoxyphene, R,R- Pseudoephedrine, Thioridazine, Cis-Tramadol, Venlafaxine HC1, 8-(-)11-nor-9- carboxy-delta 9 THC, 11-nor-9-carboxy-delta 9 THC, Amoxicillin, Propranolol, Promethazine, Phenmetrazine, Phendimetrazine, Benzocaine, Dimenhydrinate, Carbamazepine, Diazepine, Nordiazepam, Oxazepam, Acetaminophen, Caffeine, Dyphylline, Methaqualone, Theophylline, Amphetamine, Cetirizine DiHCl, Imipramine, Methamphetamine, Phencyclidine, Phenylpropanolamine, Amitriptyline, Bupivacaine HC1, Lidocaine, Methocarbamol, Nordoxepin, Pentazocine, Phenylephrine, Triamterene, Ethosuximide, Alpha-methyl-alpha-propyl succinimide, Metharbital, Barbital, Methsuximide, Phensuximide, N-Normethsuximide, Mephyton, Ethotoin, Mephobarbital, PEMA, Phenobarbital, Methyl PEMA, 10, 11- Dihydrocarbamazepine, Primidone, 5,5-Diphenylhydantoin, 4-Methylprimidone, Butabarbital, Amobarbital, Secobarbital, Hexobarbital, Azithromycin Dihydrate, Glutethimide, Methaqualone, Diazepam, Chlorpromazine, Flurazepam, AM-2201, JWH-019, JWH-081, JWH-122, CP47,497 (+/-), CP47, 497 (+/-), C8 Homologue, HU-211, JWH-200, JWH-250, Ibuprofen, Ephinephrine (+/-), Norephenephrine (+/-), Metanephrine (+/-), Normetanephrine (+/-), Vanilmandelic Acid (+/-), 5-Hydroxyindole-3-acetic acid, Homovanillic acid. Alprazolam. Cimetidine. Citalopram HBr, Clonazepam, Clopidogrel bisulfate, Fluconazole, Hydrochlorothiazide, Lamotrigine, L-Thyroxine, Methylphenidate HCl, Omeprazole, Levetiracetam, Sertraline HCl, Topiramate, Zolpidem Tartrate, Zonisamide, Amlodipine Besylate Atorvastatin Calcium Salt.
The cross reactivity of the following metabolites, opioid structural analogs and the tricyclic antidepressant imipramine was evaluated by determining the minimum concentration that would result approximately equivalent to the 2.0 ng oxycodone/10 mg hair cutoff.
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| Compounds and Metabolites | ||
|---|---|---|
| Compound | % CrossReactivity | Concentration Equivalentto 2.0 ng Oxycodone/10mg Hair |
| Hydrocodone | 80 | 2.5 |
| Codeine | 67 | 3.0 |
| 6-Acetylmorphine | 27 | 7.5 |
| Morphine | 27 | 7.5 |
| Buprenorphine | 13 | 15 |
| Hydromorphone | 10 | 20 |
| Oxymorphone | 5 | 40 |
| Imipramine | 2 | 100 |
| Oxycodone HEIA: Cross Reactivities of Structurally Related
The following compounds were shown to have no cross reactivity in the Oxycodone assay.
Lisinopril Dihydrate, Atropine, Bupropion, Cotinine, Cannabinol, Chlorpheniramine Maleate, O-Desmethylvenlafaxine, Desipramine, Doxylamine Succinate, 1S, 2R-Ephedrine, Amitriptyline, Dextromethorphan, Lidocaine, Methocarbamol, Nordoxepin, Pentazocine, Phenylephrine, Triamterene, Naproxen, Nicotine, Nortriptyline, Propoxyphene, R,R- Pseudoephedrine, Thioridazine, Cis-Tramadol, Venlafaxine HC1, 8-(-)11-nor-9- carboxy-delta 9 THC, 11-nor-9-carboxy-delta 9 THC, Amoxicillin, Propranolol, Promethazine, Phenmetrazine, Phendimetrazine, Benzocaine, Dimenhydrinate, Carbamazepine, Diazepine, Nordiazepam, Oxazepam, Acetaminophen, Caffeine, Dyphylline, Methaqualone, Theophylline, Amphetamine, Cetirizine DiHCl, Methamphetamine, Phencyclidine, Phenylpropanolamine, Amitriptyline, Bupivacaine HCl, Lidocaine, Methocarbamol, Nordoxepin, Pentazocine, Phenylephrine, Triamterene, Ethosuximide, Alpha-methyl-alphapropyl succinimide, Metharbital, Barbital, Methsuximide, Phensuximide, N-Normethsuximide, Mephenytoin, Ethotoin, Mephobarbital, PEMA, Phenobarbital, Methyl PEMA, 10, 11-Dihydrocarbamazepine, Primidone, 5,5-Diphenylhydantoin, 4-Methylprimidone, Butabarbital, Amobarbital, Secobarbital, Hexobarbital, Azithromycin Dihydrate, Glutethimide, Methaqualone, Diazepam, Chlorpromazine, Flurazepam, AM-2201, JWH-019, JWH-081, JWH-122, CP47,497 (+/-), CP47, 497 (+/-),
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| C8 Homologue, HU-211, JWH-200, JWH-250, Ibuprofen,Epinephrine (+/-), Norepinephrine (+/-), Metanephrine (+/-),Normetanephrine (+/-), Vanilmandelic Acid (+/-), 5-Hydroxyindole-3-acetic acid, Homovanillic acid, Alprazolam,Cimetidine, Citalopram HBr, Clonazepam, Clopidogrel bisulfate,Fluconazole, Hydrochlorothiazide, Lamotrigine, L-Thyroxine,Methylphenidate HCl, Omeprazole, Levetiracetam, Sertraline HCl,Topiramate, Zolpidem Tartrate, Zonisamide, Amlodipine Besylate,Atorvastatin Calcium Salt |
|---|
| Interference: The following compounds were shown to have no interference in theopiates and oxycodone assay with the exception of imipramine.Imipramine was shown to be an interferent in the oxycodone andhydrocodone assay at a concentration of $\ge$ 100 ng imipramine/10 mghair. |
| Atropine, Bupropion, Cotinine, Cannabinol, Chlorpheniraminemaleate, O- Desmethylvenlafaxine, Desipramine, DoxylamineSuccinate, 1S, 2R Ephedrine, Anhydroecgonine methyl ester,Naproxen, Nicotine, Nortriptyline, Propoxyphene, R,R-Pseudoephedrine, Thioridazine, Cis-Tramadol, Venlafaxine HCl, 8-(-)-11-nor-9-carboxy-delta-9 THC, 11-nor-9-carboxy-delta 9 THC,Amoxicillin, Propranolol, Promethazine, Phenmetrazine,Phendimetrazine, Benzocaine, Ecgonine, Glutethimide,Meprobamate, Methyprylon, Carbamazepine, Diazepam,Nordiazepam, Oxazepam, Acetaminophen, Caffeine, Dyphylline,Methaqualone, Theophylline, Amitriptyline, Dextromethorphan,Lidocaine, Methocarbamol, Nordoxepin, Pentazocine,Phenylephrine, Triamterene, Ethosuximde, α-Methyl- α-Propylsuccinimde, Metharbital, Barbital, Methsuximide,Phensuximide, N- Normethylsuximde, Mephenytoin, Ethotoin,Mephobarbital, PEMA, Phenobarbital, Methyl PEMA, 10, 11-Dihydrocarbamazepine, Primidone, Carbamazepine, 5,5-Diphenylhydantoin, 4-Methylprimidone, Glutethimide,Methaqualone, Chlorpromazine, Flurazepam, AM-2201, JWH-019,JWH-081, JWH-122, CP47, 497 (±), CP 47, 497 (±) C8Homologue, HU-211, JWH-200, JWH-250, Acetaminophen,Caffeine, Chlorpheniramine, Ibuprofen, Naproxen, R,R-(-)-Pseudoephedrine, Epinephrine (±), Metanephrine (±),Normetanephrine (±), Alprazolam, Cimetidine, Citalopram HBr |
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| Clonazepam, Clopidogrel Bisulfate, Fluconazole,Hydrochlorothiazide, Lamotrigine, L-Thyroxine, MethylphenidateHCl, Omeprazole, Amlodipine Besylate, Atorvastatin Calcium Salt,Azithromycin Dihydrate, Bupivacaine HCl Monohydrate, CetirizineDi- HCl, Dimenhydrinate, Lisinopril Dihydrate, Benzocaine. | |
|---|---|
| Calibrator: | Psychemedics prepares calibrators and control materials usingdrug stocks purchased from a commercial vendor. Each lot ofdrug is received with its specific certificate of analysis. Thecommercially obtained stock is made into calibrators andcontrols to the desired concentrations. The concentrations areconfirmed by LC/MS/MS. |
| Sample Shipping andStability DuringStorage: | Seven opiate positive samples remained positive after approximatelytwo months in storage and after shipping twice coast-to-coast in theopiates HEIA. Six opioid positive samples remained positive afterapproximately five months in storage and after shipping twice coast-to-coast in the oxycodone and hydrocodone HEIA. |
| Recovery: | The hair sample preparation for the screening HEIA is an acidicphosphate buffer extraction procedure. Recovery of opiates in theopiates HEIA was shown on average to be at least 94% completeafter 3 hours. Recovery of opioids in the oxycodone andhydrocodone HEIA was shown on average to be at least 85%complete after 3 hours. |
| Cosmetic Treatments: | Fifteen opiate-negative head hair samples were treated with perm,dye, shampoo and relaxer and the results compared to the samesamples without treatments. In each case of the fifteen samplestreated with a type of cosmetic treatment, all samples remainednegative in the opiates HEIA after the treatments. |
| Ten opiate-positive head hair samples were treated with perm, dye,shampoo and relaxer and the results compared to the same sampleswithout the treatments. In each case, the samples remained positivein the opiates HEIA after the treatments. | |
| Fifteen opioid-negative head hair samples were treated with perm,dye, shampoo and relaxer and the results compared to the samesamples without treatments. In each case of the 15 samples treatedwith a type of cosmetic treatment all samples remained negative in | |
| the oxycodone HEIA after the treatments. | |
| Ten opioid-positive head hair samples were treated with perm, dye, shampoo and relaxer and the results compared to the same samples without the treatments. In each case, the samples remained positive in the oxycodone HEIA after the treatments. | |
| Comparison Studies: | Samples positive or negative for opiates were identified using the Psychemedics opiates microplate assay (K111926), and then tested with the test device, the Psychemedics HEIA for opiates in hair. The test device (assay) has been validated using 230 individual hair samples collected anonymously from a workplace setting. |
| The stored hair samples were then tested using Psychemedics' LC/MS/MS confirmatory assay, to compare the Psychemedics HEIA results with the LC/MS/MS results. The studies comparing the HEIA with LC/MS/MS documented the source of hair (head or body) and other demographics as available. The comparison of the Psychemedics Opiates HEIA with LC/MS/MS is shown in the following tables. |
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| Opiates HEIAResult | Washed LC/MS/MS Result, ng Morphine/10 mg hair (% of cutoffcalibrator) | |||
|---|---|---|---|---|
| < 1.0 (< 50%below cutoff) | 1.0 – 1.99 (≥ 50%below cutoff tocutoff) | 2.0 – 3.0 (cutoffto ≤ 50% abovecutoff) | > 3.0 (> 50%above cutoff) | |
| Positive | 43 | 3 | 14 | 42 |
| Negative | 118 | 10 | 0 | 0 |
The presence of codeine, 6-AM, and morphine was detected by LC-MS/MS in the discordant results observed, and the presence of these analytes contributed to the positive results observed by the screening assay.
Samples positive or negative for opioids were identified using the Psychemedics oxycodone microplate assay (K123799) or opiates microplate assay (K111926), and then tested with the test device, the Psychemedics HEIA for oxycodone in hair. The test device (assay) has been validated using 219 individual hair samples collected anonymously from a workplace setting.
The stored hair samples were then tested using Psychemedics' LC/MS/MS confirmatory assay, to compare the Psychemedics HEIA results with the LC/MS/MS results. The studies comparing
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the HEIA with LC/MS/MS documented the source of hair (head or body) and other demographics as available. The comparison of the Psychemedics Oxycodone HEIA with LC/MS/MS is shown in the following tables.
| OxycodoneHEIA Result | < 1.0 (< 50%below cutoff) | 1.0 – 1.99 (≥ 50%below cutoff tocutoff) | 2.0 – 3.0 (cutoffto≤ 50% abovecutoff) | > 3.0 (> 50%above cutoff) |
|---|---|---|---|---|
| Positive | 48 | 8 | 15 | 31 |
| Negative | 103 | 14 | 0 | 0 |
The presence of hydrocodone was detected by LC-MS/MS in the discordant results observed, and the presence of this analyte contributed to the positive results observed by the screening assay.
The Psychemedics HEIA for opiates in hair is substantially Conclusion: equivalent to the predicate based on performance studies, including precision, specificity and interference (including cosmetic effects).
The Psychemedics HEIA for oxycodone in hair is substantially equivalent to the predicate based on performance studies, including precision, specificity and interference (including cosmetic effects).
§ 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).