(414 days)
The Psychemedics homogeneous enzyme immunoassay for cocaine in hair is an enzyme immunoassay for the preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair for the purpose of identifying cocaine use. This product is intended exclusively for in-house professional use and not for sale to anyone.
The Psychemedics EIA Cocaine Assay provides only a preliminary analytical test results, a more specific alternate chemical method (e.g. LC/MS/MS) must be used. Clinical consideration and professional judgement should be applied to the interpretation of any drug-of-abuse test result.
The homogeneous enzyme immunoassay (HEIA) test consists of two parts; a pre-analytical hair treatment procedure (to extract cocaine from the solid hair matrix to a measurable liquid matrix) and the screening assay, the Psychemedics Cocaine 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 Cocaine HEIA consists of reagents R1 (anti-cocaine monoclonal antibody with substrate) and R2 (cocaine labeled recombinant G6PDH).
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device Name: Psychemedics Homogeneous Enzyme Immunoassay for Cocaine in Hair
Indications for Use: Preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair, for identifying cocaine use. Intended for in-house professional use only. Positive results require confirmation with a more specific alternate chemical method (e.g., LC/MS/MS).
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" with specific pass/fail metrics in a table format. Instead, it details various performance studies and their results to demonstrate substantial equivalence to a predicate device. I've extracted the relevant performance metrics and will organize them as an "acceptance criteria" table for clarity, inferring the implied acceptance for each from the reported results ("all good", "no cross-reactivity", "remained positive/negative").
| Acceptance Criteria Category | Implicit Acceptance Criteria / Goal | Reported Device Performance |
|---|---|---|
| Precision (Intra-Assay) | Consistent classification (NEG/POS) at various concentrations around cutoff. | At -100%, -75%, -50%, -25% of cutoff, all 8 replicates were NEG. At +25%, +50%, +75%, +100% of cutoff, all 8 replicates were POS. |
| Precision (Inter-Assay) | Consistent classification (NEG/POS) at various concentrations around cutoff across multiple assays. | At -100%, -75%, -50%, -25% of cutoff, all 80 replicates were NEG. At +25%, +50%, +75%, +100% of cutoff, all 80 replicates were POS. |
| Cross-Reactivity (Related Compounds) | Low cross-reactivity for structurally related compounds and metabolites to minimize false positives. | Benzoylecgonine: 2.0% cross-reactivity (250 ng/10 mg hair equivalent). Norcocaine: 20% cross-reactivity (25 ng/10 mg hair equivalent). Cocaethylene: 55.5% cross-reactivity (9 ng/10 mg hair equivalent). Ecgonine, Ecgonine Methyl Ester, Anhydroecgonine Methyl Ester: <1% cross-reactivity (>500 ng/10 mg hair equivalent). (This indicates that significantly higher concentrations of these substances are required to elicit a positive result compared to cocaine, which is generally considered acceptable for preliminary screening). |
| Interference (Other Compounds) | No interference from common medications or other substances. | Listed a wide array of compounds (e.g., Lisinopril Dihydrate, Atropine, Bupropion, Cannabinol, common prescription drugs, other drug-of-abuse metabolites) that showed no cross-reactivity and no interference in the cocaine assay. (This implies that the assay is specific enough not to react with many other substances). |
| Sample Shipping Stability | Cocaine detection should remain stable after storage and shipping. | Five cocaine positive samples remained positive after approximately 6 months in storage and after shipping twice coast-to-coast. (Acceptable stability shown). |
| Recovery | Adequate recovery of cocaine during the hair extraction process. | Recovery of cocaine in the method shown on average to be at least 81% complete after 2 hours. (Acceptable recovery). |
| Cosmetic Treatments Effect | Cosmetic treatments should not alter detection accuracy for positive or negative samples. | Negative Samples: 10 cocaine-negative head hair samples treated with perm, dye, shampoo, and relaxer remained negative. Positive Samples: 7 cocaine-positive head hair samples treated with perm, dye, shampoo, and relaxer remained positive. (Acceptable, as cosmetic treatments did not affect results). |
| Clinical Performance (Study 1) | High concordance with LC/MS/MS with expected discordance attributable to washing for confirmation. | Total Samples Tested: 215 (123 negative, 92 positive by immunoassay).HEIA Positive / LC/MS/MS > 5 ng/10mg: 89 samples.HEIA Negative / LC/MS/MS < 2.5 ng/10mg: 119 samples.Discordant (HEIA POS / LC/MS/MS NEG (2.5-4.99)): 3 samples. The document explains these as anticipated due to washing before LC/MS/MS, which removes environmental/sweat-derived contaminants. |
| Clinical Performance (Study 2) | High concordance with LC/MS/MS (unwashed and washed), with expected discordance. | HEIA Positive / Unwashed LC/MS/MS > 5 ng/10mg: 39 samples.HEIA Negative / Unwashed LC/MS/MS < 2.5 ng/10mg: 44 samples.HEIA Positive / Washed LC/MS/MS > 5 ng/10mg: 39 samples.HEIA Negative / Washed LC/MS/MS < 2.5 ng/10mg: 48 samples.Discordant (HEIA POS / LC/MS/MS NEG (2.5-4.99)): - Unwashed LC/MS/MS: 2 samples. - Washed LC/MS/MS: 2 samples. These discordant samples confirmed within 15% of the cutoff unwashed, and showed decreased concentration after washing, supporting the explanation for discordance due to external contamination/sweat. |
2. Sample Size Used for the Test Set and Data Provenance
-
Sample Size for Test Set:
- Precision Studies: 8 replicates per concentration for Intra-Assay, 80 replicates per concentration for Inter-Assay.
- Cross-Reactivity/Interference: Not explicitly stated as a number of samples, but presumably multiple replicates for each compound tested.
- Cosmetic Treatments: 10 negative hair samples and 7 positive hair samples.
- Comparison Study 1: 215 individual hair samples (123 negative, 92 positive by immunoassay).
- Comparison Study 2: An "additional set of samples" (unspecified number) for which LC/MS/MS data is available for both unwashed and washed samples. The tables present data for a total of 41 positive samples and 51 negative samples relative to the cutoff (for unwashed LC/MS/MS comparison). The sample characteristics table shows 65 Head hair, 27 Body hair, 79 Male, 13 Female, 47 Brown, 39 Black, 6 Salt/Pepper hair for the combined comparison study. Based on table counts, there were 91 samples in Study 2 (41 positive, 50 negative across various LC/MS/MS comparisons).
-
Data Provenance:
- Comparison Study 1: Samples collected anonymously from a workplace setting.
- Comparison Study 2: Source of hair (head or body) and other demographics were documented.
- General indication that materials (drug stocks) are purchased from commercial vendors; calibrators and controls are made in-house.
The study appears to be retrospective, as "stored hair samples were then tested" and samples were "collected anonymously from a workplace setting" for Study 1, and "additional set of samples were identified using the Psychemedics cocaine microplate assay and the test device" for Study 2.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document refers to LC/MS/MS as the "more specific alternate chemical method" and "confirmatory assay" to establish the ground truth for cocaine presence and concentration. It does not mention human experts establishing the ground truth or their qualifications. The ground truth is analytical/laboratory-based.
4. Adjudication Method for the Test Set
There was no human expert adjudication method mentioned (e.g., 2+1, 3+1). The ground truth was established purely through analytical chemistry (LC/MS/MS testing).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an automated in vitro diagnostic (IVD) assay designed for preliminary detection of a substance. It does not involve human readers interpreting images or data, nor does it aim to show how much human readers improve with AI assistance. The comparison is between the new homogeneous immunoassay and a laboratory confirmation method (LC/MS/MS).
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies performed are essentially standalone performance evaluations of the device (the immunoassay) against the gold standard (LC/MS/MS). The device operates independently of human interpretation for its initial qualitative result. The "human-in-the-loop" aspect comes only after a positive preliminary result, where a professional judgment along with confirmation by LC/MS/MS is required.
7. The Type of Ground Truth Used
The ground truth used is analytical confirmation by LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). This is a highly specific and sensitive laboratory method for identifying and quantifying substances. For the training set, it is also supported by "certificate of analysis" for the drug stocks.
8. The Sample Size for the Training Set
The document does not explicitly state the sample size used for the training set. The performance studies described are for the validation of the device (effectively the test set). For the calibrators and control materials, it states "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." This implies that the initial "calibration" or establishment of the assay's operational parameters would have been done using these certified drug stocks, but a specific "training set" size for a machine learning model (which this device is not) is not applicable here.
9. How the Ground Truth for the Training Set Was Established
For the calibrators and control materials (which would serve a similar function to a training set in establishing the assay's performance characteristics), the ground truth was established by:
- Certificates of Analysis for drug stocks purchased from a commercial vendor.
- Confirmation by LC/MS/MS of the concentrations of the in-house prepared calibrators and controls.
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June 25, 2021
Psychemedics Corporation Neil Stowe Principal Scientist 5832 Uplander Way Culver City, California 90230
Re: K201228
Trade/Device Name: Psychemedics Homogeneous Enzyme Immunoassay for Cocaine in Hair Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and Cocaine Metabolite Test System Regulatory Class: Class II Product Code: JXO Dated: October 26, 2020 Received: October 27, 2020
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.
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
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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) K201228
Device Name
Psychemedics Homogeneous Enzyme Immunoassay for Cocaine in Hair
Indications for Use (Describe)
The Psychemedics homogeneous enzyme immunoassay for cocaine in hair is an enzyme immunoassay for the preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair for the purpose of identifying cocaine use. This product is intended exclusively for in-house professional use and not for sale to anyone.
The Psychemedics EIA Cocaine Assay provides only a preliminary analytical test results, a more specific alternate chemical method (e.g. LC/MS/MS) must be used. Clinical consideration and professional judgement should be applied to the interpretation of any drug-of-abuse test result.
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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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: | K201228 | ||
|---|---|---|---|
| Submitted By: | Psychemedics Corporation5832 Uplander WayCulver City, CA 90230TEL: 310 216 7776FAX: 310 216 6662 | ||
| Submission Contact: | Neil Stowe | ||
| Date Prepared: | 10-26-2020 | ||
| Device Trade Name: | Psychemedics Homogeneous Enzyme Immunoassay for Cocaine in Hair | ||
| Predicate Device: | Psychemedics Microplate EIA for Cocaine in Hair, K111925 | ||
| Product Code: | JXO | ||
| Device/Classification Name: | 21 CFR 862.3250 Cocaine and Cocaine Metabolite Test System, Classification II | ||
| Intended Use: | The Psychemedics homogeneous enzyme immunoassay for cocaine in hair is an enzyme immunoassay for the preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair for the purpose of identifying cocaine use. This product is intended exclusively for in-house professional use and is not for sale to anyone.The Psychemedics HEIA Cocaine Assay provides only a preliminary analytical test result. To confirm positive results, a more specific alternate chemical method (e.g. LC/MS/MS) must be used. Clinical consideration and professional judgement should be applied to the interpretation of any drug-of-abuse test result. | ||
| Device Description: | The homogeneous enzyme immunoassay (HEIA) test consists of two parts; a pre-analytical hair treatment procedure (to extract cocaine from the solid hair matrix to a measurable liquid matrix) and the screening assay, the Psychemedics Cocaine 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. |
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| The Psychemedics Cocaine HEIA consists of reagents R1 (anti-cocainemonoclonal antibody with substrate) and R2 (cocaine labeled recombinantG6PDH). |
|---|
| Sample Collection and Stability: A sample of hair should be cut as close as possible to the skin. The hair is placedin a V-shaped aluminum foil sample holder with the root end of the hairprotruding beyond the slanted edge of the foil. The aluminum foil is crimpedaround the sample, securing the hair specimen firmly into place within the foil.The hair sample, crimped within the foil, is placed in a sample acquisition cardenvelope and the envelope is sealed with a tamper-evident seal. Hair specimensare kept at ambient temperature in a secure location until they are shippedwithout refrigeration to the laboratory. Stability of cocaine in hair samplesstored at room temperature has been shown for approximately 6 months.Cocaine in samples shipped coast-to-coast twice was stable. |
| Materials Required: Hair sample collection kit, HEIA for Cocaine, automated clinical chemistryanalyzer, LC/MS/MS for confirmation. |
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Comparison with Predicate:
| Item | Proposed Device | Psychemedics Cocaine Assay,K111925 |
|---|---|---|
| Indications/Intended Use | The Psychemedics homogeneousenzyme immunoassay for cocainein hair is an enzyme immunoassayfor the preliminary qualitativedetection of cocaine in human headand body hair using a cocainecalibrator of 5 ng/10 mg hair for thepurpose of identifying cocaine use.This product is intendedexclusively for in-houseprofessional use and not for sale toanyone.The Psychemedics EIA CocaineAssay provides only a preliminaryanalytical test result. To confirmpositive results, a more specificalternate chemical method (e.g.LC/MS/MS) must be used. Clinicalconsideration and professionaljudgement should be applied to theinterpretation of any drug-of-abusetest result. | The Psychemedics Microplate EIAfor Cocaine is an enzymeimmunoassay (EIA) for thepreliminary qualitative detection ofcocaine in human head and bodyhair samples using a cocainecalibrator at 5 ng/10 mg hair cutofffor the purpose of identifyingcocaine use. This product isintended exclusively for in-houseprofessional use and not for sale toanyone. The test is not intended forover-the-counter sale to non-professionals.The Psychemedics EIA CocaineAssay provides only a preliminaryanalytical test result. To confirmpositive results, a more specificalternate chemical method (e.g.LC/MS/MS) must be used. Clinicalconsideration and professionaljudgement should be applied to theinterpretation of any drug-of-abusetest result. |
| Product Code | JXO | JXO |
| Measurand | Cocaine | Cocaine |
| Test System | Psychemedics HomogeneousEnzyme Immunoassay for Cocainein Hair | Psychemedics Microplate EIA forCocaine in Hair |
| Sample Matrix | Human Hair | Human Hair |
| Method of Measurement | Automated Clinical ChemistryAnalyzer at 340 nm | Microplate Reader at 450 nm |
| Type of Test | Enzyme Immunoassay | Enzyme Immunoassay |
| Extraction Method | Acidic aqueous buffer | Patented Digestion Method |
| Confirmation Method | LC/MS/MS | LC/MS/MS |
Performance Testing Summary: Precision studies were performed by spiking negative hair with previously LC/MS/MS validated calibrator and control solutions to achieve concentrations of negative, the cutoff calibrator of 5 ng cocaine/10 mg hair, and +/- 75%, +/-50% and +/-25% of the cutoff calibrator.
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| Summary Intra-Assay Precision | Summary Inter-Assay Precision | |||||
|---|---|---|---|---|---|---|
| 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 cocaine structural analogs was evaluated by determining the minimum concentration that would result approximately equivalent to the 5.0 ng cocaine/10 mg hair cutoff.
| Cross Reactivities of Structurally Related Compounds and Metabolites | ||
|---|---|---|
| Compound | % CrossReactivity | Concentration Equivalent to5.0 ng Cocaine/10 mg Hair |
| Benzoylecgonine | 2.0 | 250 |
| Norcocaine | 20 | 25 |
| Cocaethylene | 55.5 | 9 |
| Ecgonine | <1 | >500 |
| Ecgonine Methyl Ester | <1 | >500 |
| Anhydroecgonine Methyl Ester | <1 | >500 |
The following compounds were shown to have no cross reactivity in the Cocaine assay.
Lisinopril Dihydrate, Atropine, Bupropion, Cotinine, Cannabinol, Chlorpheniramine Maleate, O-Desmethylvenlafaxine, Desipiramine, Doxylamine Succinate, 1S, 2R-Ephedrine, Amitriptyline, Dextromethorphan, Lidocaine, Methocarbamol, Nordoxepin, Pentazocine, Phenylephrine, Triamterene, Naproxen, Nicotine, Nortriptyline, Propoxyphene, R,R-Pseudoepedrine, Thioridazine, Cis-Tramadol, Venlafaxine HCl, 8-(-)11-nor-9carboxy-delta 9 THC, 11-nor-9-carboxy-delta 9 THC, Amoxicillin, Propanolol, Promethazine, Phenmetrazine, Phendimetrazine, Benzocaine, Dimenhydrinate, Metanephrin, Carbamazepine, Diazepine, Nordiazepam, Oxazepam, Acetominophen, Caffeine, Dyphylline, Methaqualone, Theophylline, Amphetamine, Cetrizine DiHCl, Imipramine, Methamphetamine, Phencyclidine, Phenylpropanolamine, Amitryptiline, Bupivacaine HCl, Lidocaine, Methocarbamol, Nordoxepin, Pentazocine, Pheynylephrine, Triamterene, Ethosuximide, Alpha-methyl-alpha-propyl succinimide, Metharbital, Barbital, Mehsuximde, Phensuximide, N-Normethsuximide, Mephyton, Ethotoin, Mephobarbital, PEMA, Phenobarbital, Methyl PEMA, 10, 11-Dihydrocarbamazepine, Primidone, 5,5-Diphenylhydantoin, 4-Methylprimidone, Butabarbital, Amobarbital, Secobarbital, Hexobarbital, Azithromyocin 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,
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| Ephinephrine (+/-), Norephenephrine (+/-), Metanephrine (+/-),Normetanephrine (+/-), Vanilmandelic Acid (+/-), 5-Hydroxyindole-3-aceticacid, Homovanillic acid, Alprazolam, Cimetidine, Citalopram HBr,Clonazepam, Clopidogrel bisulfate, Fluconazole, hydrochlorothiazide,Lamotrigeine, L-Thyroxine, Methylphenidate HCl, Omeprazole, Levetiracetam,Sertaline HCl, Topiramate, Zolpidem Tartrate, Zonisamide, AmlopidineBesylate Atorvastatin Calcium Salt | |
|---|---|
| Interference: | The following compounds were shown to have no interference in the cocaineassay. |
| Atropine, Bupropion, Cotinine, Cannabinol, Chlorpheniramine maleate, O-Desmethylvenlafaxine, Desipiramine, Doxylamine Succinate, 1S, 2R Ephedrine,Anhydroecgonine methyl ester, Naproxen, Nicotine, Nortriptyline,Propoxyphen, R,mR-Pseudoephedrine, Thioridazine, Cis-Tramadol,Venlafaxine HCl, 8-(-)-11-nor-9-carboxy-delta-9 THC, 11-nor-9-carboxy-delta9 THC,Amoxicillin, Propanolol, Promethazine, Phenmetrazine,Phendimetrazine, Benzocaine, Ecgonine, Metanephrin, Glutethimide,Meprobamate, Methyprylon, Carbamazepine, Diazepam, Nordiazepam,Oxazapam, Acetominophen, Caffeine, Dyphylline, Methaqualone,Theophylline, Amitryptiline, Dextromethorphan, Lidocaine, Methocarbamol,Nordoxepin, Pentazocine, Phenylephrine, Triamterene, Ethosuximde, a-Methyl-a-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 (±) C8 Homologue, HU-211, JWH-200,JWH-250, Acetominophen, Caffeine, Chlorpheniramine, Ibuprogen, Naproxen,R,R-(-)-Pseudoepedrine, Epinephrine (±), Metanephrine (±), Normetanephrine(±), Alprazolam, Cimetidine, Citalopram HBr, Clonazepam, ClopidogrelBisulfate, Fluconazole, Hydorchlorothiazide, Lamotrigine, L-Thyroxine,Methylphenidate HCl, Omeprazole, Amlopidine Besylate, Atorvastatin CalciumSalt, Azithromycin Dihydrate, Bupivacaine HCl Monohydrate, Cetirizine Di-HCl, Dimenhydrinate, Lisinopril Dihydrate, Propanolol, Benzocaine,Metanephrin | |
| Calibrator: | Psychemedics prepares calibrators and control materials using drug stockspurchased from a commercial vendor. Each lot of drug is received with itsspecific certificate of analysis. The commercially obtained stock is made intocalibrators and controls to the desired concentrations. The concentrations areconfirmed by LC/MS/MS. |
| Sample Shipping StabilityDuring Storage: | Five cocaine positive samples remained positive after approximately 6 monthsin storage and after shipping twice coast-to-coast. |
| Recovery: | The hair sample preparation for the screening HEIA is a phosphate bufferextraction procedure. Recovery of cocaine in the method was shown on averageto be at least 81% complete after 2 hours. |
| Cosmetic Treatments: | Ten cocaine-negative head hair samples were treated with perm, dye, shampooand relaxer and the results compared to the same samples without treatments. Ineach case of the 10 samples treated with a type of cosmetic treatment, allsamples remained negative after the treatments.Seven cocaine-positive head hair samples were treated with perm, dye, shampooand relaxer and the results compared to the same samples without thetreatments. In each case, the samples remained positive after the treatments. |
| Comparison Studies: | Study 1:Samples positive or negative for cocaine were identified using the Psychemedicscocaine microplate assay (K111925), and then tested with the test device, thePsychemedics HEIA for cocaine in hair. The test device (assay) has beenvalidated using 215 individual hair samples collected anonymously from aworkplace setting. One hundred and twenty-three negative samples and 92positive samples were identified by the immunoassays.The stored hair samples were then tested using Psychemedics' LC/MS/MSconfirmatory assay, to compare the Psychemedics HEIA results with the washedLC/MS/MS results. The studies comparing the HEIA with washed LC/MS/MSdocumented the source of hair (head or body) and other demographics asavailable. The comparison of the Psychemedics Cocaine HEIA with washedLC/MS/MS is shown in the following tables. |
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| Table 1. Comparison of Cocaine HEIA Screening Results with LC/MS/MS of Washed Samples | ||||
|---|---|---|---|---|
| HEIA Result | LC/MS/MS Result, ng Cocaine/10 mg hair (% of cutoff calibrator) | |||
| < 2.50 (< 50% below cutoff) | 2.50 – 4.99 (≥ 50% below cutoff to cutoff) | 5.00 – 7.50 (cutoff to ≥ 50% above cutoff) | > 7.50 (> 50% above cutoff) | |
| Positive | 0 | 3 | 14 | 75 |
| Negative | 119 | 4 | 0 | 0 |
Discordant Results: Positive HEIA/Negative LC/MS/MS
Washing of hair before confirmation: exclusion of potential environmental contamination and/or sweat-derived drug from hair analysis results can result in APPARENT discordant results. Ingested drugs are present in perspiration, which settles on the hair and requires removal if the hair analysis result is to reflect amount of drug ingested rather than exposure to the sweat-derived drug. Drug could also be present as a result of environmental contamination (e.g., powder, smoke). Hair is not washed prior to screening, as it would not be reasonable to wash hundreds of negative hair samples; i.e., samples that are negative without washing. Thus, it is expected that the washing performed before LC/MS/MS confirmation of presumptive positives removes external drug and the confirmation results may then be lower than the screening may have predicted without the consideration of sweat-derived drug and/or drug from environmental contamination.
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| Table 2. Discordant Results Between HEIA and Washed LC/MS/MS | |||
|---|---|---|---|
| Sample | HEIA Result | LC/MS/MS Result (ng Cocaine/10 mg hair) | Comment |
| 1 | POS | 3.49 | Samples are screened by HEIA without hair washing.LC/MS/MS is performed only after washing once with isopropanol, 3 times 30 minutes with 0.01 M phosphate buffer and 2 times with 0.01 M phosphate buffer for 60 minutes. Thus, it is expected that some samples will be negative by LC/MS/MS after washing. |
| 2 | POS | 3.75 | |
| 3 | POS | 4.27 |
Study 2:
An additional set of samples were identified using the Psychemedics cocaine microplate assay and the test device. These samples were tested using Psychemedics' LC/MS/MS confirmatory assay both with and without prior washing of the samples, to compare the Psychemedics HEIA results with unwashed LC/MS/MS results and washed LC/MS/MS results. The studies comparing the HEIA with unwashed and washed LC/MS/MS documented the source of hair (head or body) and other demographics as available. The comparison of the Psychemedics Cocaine HEIA with unwashed and washed LC/MS/MS is shown in the following tables.
| Table 3. Comparison of Cocaine HEIA Screening Results with Unwashed Cocaine LC/MS/MS | ||||
|---|---|---|---|---|
| HEIA Result | LC/MS/MS Result, ng Cocaine/10 mg hair (% of cutoff calibrator) | |||
| < 2.50 (< 50% below cutoff) | 2.50 – 4.99 (≥ 50% below cutoff to cutoff) | 5.00 – 7.50 (cutoff to ≤ 50% above cutoff) | > 7.50 (> 50% above cutoff) | |
| Positive | 0 | 2 | 4 | 35 |
| Negative | 44 | 7 | 0 | 0 |
| Table 4. Comparison of Cocaine HEIA Screening Results with Washed Cocaine LC/MS/MS | ||||
|---|---|---|---|---|
| HEIA Result | LC/MS/MS Result, ng Cocaine/10 mg hair (% of cutoff calibrator) | |||
| < 2.50 (< 50% below cutoff) | 2.50 – 4.99 (≥ 50% below cutoff to cutoff) | 5.00 – 7.50 (cutoff to ≤ 50% above cutoff) | > 7.50 (> 50% above cutoff) | |
| Positive | 0 | 2 | 8 | 31 |
| Negative | 48 | 3 | 0 | 0 |
Discordant Results: Positive HEIA/Negative LC/MS/MS
Two samples in the second study were positive by HEIA and Negative by unwashed and washed LC/MS/MS. Both samples confirmed within 15% of the LC/MS/MS cutoff when unwashed. After washing, both samples decreased in cocaine concentration.
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| Table 5. Discordant Results Between HEIA and Unwashed LC/MS/MS | |||
|---|---|---|---|
| Sample | HEIA Result | LC/MS/MS Result (ng Cocaine/10 mg hair) | Comment |
| 1 | POS | 4.43 | Although samples 1 and 2 confirmed negative after screening positive, they confirmed within 15% of the 5 ng/10 mg cocaine LC/MS/MS cutoff. |
| 2 | POS | 4.96 |
| Sample | HEIA Result | LC/MS/MS Result (ng Cocaine/10 mg hair) | Comment |
|---|---|---|---|
| 1 | POS | 3.75 | Samples 1 and 2 confirmed negative after screening positive and washing before LC/MS/MS. Confirmation of these samples after washing found a decrease in cocaine concentration relative to the unwashed samples. |
| 2 | POS | 4.27 |
| Table 7. Comparison of Unwashed and Washed Samples | |||
|---|---|---|---|
| Sample # | Unwashed LC/MS/MS (ng Cocaine/10 mg hair) | Washed LC/MS/MS (ng Cocaine/10 mg hair) | Comment |
| 1 | 4.43 | 3.75 | |
| 2 | 4.96 | 4.27 | Both samples 1 and 2 had a decrease in cocaine concentration after washing. |
| Table 8. Unwashed and Washed Comparison Study Sample Characteristics | ||||||||
|---|---|---|---|---|---|---|---|---|
| Hair Source | Gender | Hair Color | ||||||
| Head | Body | Male | Female | Brown | Black | Salt/Pepper | ||
| # of Samples | 65 | 27 | 79 | 13 | 47 | 39 | 6 |
Conclusion:
The Psychemedics HEIA for cocaine in hair is substantially equivalent based on acceptable performance studies, including precision, specificity and interference (including cosmetic effects).
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).