Evidence MultiSTAT DOA Urine MultiPlex, Evidence MultiSTAT
Device Facts
| Record ID | K220451 |
|---|---|
| Device Name | Evidence MultiSTAT DOA Urine MultiPlex, Evidence MultiSTAT |
| Applicant | Randox Laboratories Limited |
| Product Code | DJG · Clinical Toxicology |
| Decision Date | Oct 5, 2023 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3650 |
| Device Class | Class 2 |
Indications for Use
The Evidence MultiSTAT DOA Urine MultiPlex is intended for use with the Evidence MultiSTAT. The Evidence MultiSTAT is an analyzer intended for the qualitative determination of parent drug molecule and metabolites of drugs in human urine at the associated cutoffs. The Evidence MultiSTAT DOA Urine MultiPlex detects the following drugs at the following cut-offs: Benzodiazepines I (Oxazepam, 200 ng/mL), Methamphetamine (S-(+)-Methamphetamine, 500 ng/mL), Noroxycodone (Noroxycodone, 100 ng/mL), Methadone ((±)-Methadone, 300 ng/mL). The Evidence MultiSTAT DOA Urine MultiPlex provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and/or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained. For in vitro diagnostic use only.
Device Story
Evidence MultiSTAT is a benchtop, fully automated biochip array system for clinical toxicology. Input: human urine sample. Process: sample processed in self-contained, sealed biochip cartridge containing immobilized antibodies; competitive chemiluminescent immunoassay performed; drug in specimen competes with HRP-labeled drug for antibody binding sites; increased drug concentration reduces chemiluminescence. Output: light signal detected by internal CCD camera; analyzer software quantifies light output to determine qualitative drug presence based on pre-set cutoffs. Used in clinical settings by trained personnel. Output assists clinicians in preliminary drug screening; requires confirmation via GC/MS or LC/MS/MS. Benefits: simultaneous multi-analyte detection from single sample; automated workflow reduces manual handling.
Clinical Evidence
No clinical trials performed. Evidence consists of analytical performance studies: precision/reproducibility (40 replicates per analyte), interference testing (endogenous/exogenous compounds), and method comparison against LC/MS/MS using clinical urine samples (n=137 for Methamphetamine, n=80 for Noroxycodone, n=133 for Benzodiazepines, n=287 for Methadone).
Technological Characteristics
Benchtop automated analyzer; Biochip Array System; competitive chemiluminescent immunoassay; CCD camera for signal detection. Reagents: HRP-labeled drug derivatives, biochip with immobilized antibodies. Single-use sealed cartridges. Standards: IEC 60601-1-2 (safety/EMC), CLSI EP12-A2 (qualitative performance).
Indications for Use
Indicated for qualitative detection of drugs of abuse (Benzodiazepines, Methamphetamine, Noroxycodone, Methadone) in human urine samples. Intended for prescription use.
Regulatory Classification
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.
Special Controls
*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).
Predicate Devices
- PROFILE®-V MEDTOXScan® Drugs of Abuse Test System (K091454)
Related Devices
- K221550 — Evidence MultiSTAT DOA Urine MultiPlex · Randox Laboratories Limited · Oct 5, 2023
- K250741 — Evidence MultiSTAT DOA Urine MultiPlex · Randox Laboratories Limited · Jan 23, 2026
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT
## I Background Information:
A 510(k) Number
K220451
B Applicant
Randox Laboratories Limited
C Proprietary and Established Names
Evidence MultiSTAT DOA Urine MultiPlex, Evidence MultiSTAT
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 21 CFR 862.3650 – Opiate Test System | TX - Clinical Toxicology |
| DJR | Class II | 21 CFR 862.3620 – Methadone test system | TX - Clinical Toxicology |
| JXM | Class II | 21 CFR 862.3170 – Benzodiazepine Test System | TX - Clinical Toxicology |
| DJC | Class II | 21 CFR 862.3610 – Methamphetamine Test System | TX - Clinical Toxicology |
| JJE | Class I | 21 CFR 862.2160 – Discrete photometric chemistry analyzer for clinical use | CH – Clinical |
## II Submission/Device Overview:
A Purpose for Submission:
New device
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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K220451 - Page 2 of 22
B Measurand:
Methamphetamine, Noroxycodone, Benzodiazepines, and Methadone
C Type of Test:
Chemiluminescent immunoassay
III Intended Use/Indications for Use:
A Intended Use(s):
See Indications for Use below.
B Indication(s) for Use:
The Evidence MultiSTAT DOA Urine MultiPlex is intended for use with the Evidence MultiSTAT. The Evidence MultiSTAT is an analyzer intended for the qualitative determination of parent drug molecule and metabolites of drugs in human urine at the associated cutoffs.
The Evidence MultiSTAT DOA Urine MultiPlex detects the following drugs at the following cut-offs:
| Analyte | Analyte in Cut Off Material | Cut-Off |
| --- | --- | --- |
| Benzodiazepines I | Oxazepam | 200 ng/mL |
| Methamphetamine | S-(+)-Methamphetamine | 500 ng/mL |
| Noroxycodone | Noroxycodone | 100 ng/mL |
| Methadone | (±)-Methadone | 300 ng/mL |
The Evidence MultiSTAT DOA Urine MultiPlex provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and/or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.
For in vitro diagnostic use only.
C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
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D Special Instrument Requirements:
Evidence MultiSTAT
IV Device/System Characteristics:
A Device Description:
The Evidence MultiSTAT is a benchtop fully automated Biochip Array System analyzer. The Evidence MultiSTAT DOA Urine MultiPlex test kit components include a sealed urine test cartridge which contains materials for the determination of the claimed analytes at the associated cut-off.
This submission (k220451) contains the review for the Evidence MultiSTAT and following Randox Evidence MultiSTAT DOA Urine MultiPlex claimed analytes at the associated cut off concentrations: Methamphetamine at 500 ng/ml, Noroxycodone at 100 ng/ml, Oxazepam at 200 ng/ml, and Methadone at 300 ng/ml.
Submission k221550 includes the following claimed analytes and associated cut off concentrations; Phenobarbital at 200 ng/ml, Tramadol at 200 ng/ml, Phencyclidine at 25 ng/ml, Buprenorphine at 5 ng/ml, 6-Acetylmorphine at 10 ng/ml.
The Randox Evidence MultiSTAT DOA Urine MultiPlex test kit is comprised of:
- 12 x Urine Test Cartridges
- 6 x 1mL Urine Cut Off Material (lyophilized)
- 4 x 1mL Urine Positive Control Material (lyophilized)
- 2 x 10mL Reconstitution Buffer
- 1 x USB which contains batch specific update and Instructions for Use (IFU)
- 1 x Batch Barcodes
Each kit is supplied with the Evidence MultiSTAT Accessory Kit which contains:
- 12 x MultiSTAT Tip Cartridges
- 1 x Tip/Waste Cartridge
- 6 x 1000 μl Pipette Tip
- 1 x Liquid Absorber
The Reagent Composition of the test kit is comprised of:
- MultiSTAT DOA Urine MultiPlex Assay Diluent - 20 mM phosphate buffer, pH 7.2 containing protein, detergents, and preservatives. This is contained within the cartridge.
- MultiSTAT DOA Urine MultiPlex Conjugate - 20 mM Tris based buffer, pH 7.0 containing protein, preservatives, and horseradish peroxidase - labelled drug derivatives. This is contained within the cartridge.
K220451 - Page 3 of 22
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- MultiSTAT DOA Urine MultiPlex Biochip - Solid substrate containing immobilized antibody discrete test regions. This is contained within the cartridge.
- MultiSTAT DOA Urine MultiPlex Wash Buffer - 20 mM Tris buffered saline, pH 7.4, containing surfactant and preservatives. This is contained within the cartridge.
- LUM-EV934/PX - Luminol-EV934 and Peroxide are contained within the cartridge and are mixed in a ratio of 1:1 by the analyser to give the working signal reagent
- MultiSTAT DOA Urine MultiPlex Cut Off - Lyophilised, 20 mM phosphate buffer, pH 7.2 containing stabilizers, preservatives and drug concentrations at the assay cut off values.
- MultiSTAT DOA Urine MultiPlex Positive Control - Lyophilised, 20 mM phosphate buffer, pH 7.2 containing stabilizers, preservatives, and drug concentrations at 50% higher than the cut-off values.
- MultiSTAT Reconstitution Buffer – A solution at a neutral pH containing preservatives.
## B Principle of Operation:
The candidate device performs simultaneous detection of multiple analytes from a single sample. The core technology is the Randox Biochip, a solid-state device containing an array of discrete test regions containing immobilized antibodies specific to different Drugs of Abuse (DOA) compound classes. A competitive chemiluminescent immunoassay is used for the DOA assays with the drug in the specimen and drug labelled with horseradish peroxidase (HRP) being in direct competition for the antibody binding sites. Increased levels of drug in a specimen will lead to reduced binding of drug labelled with HRP and thus a reduction in chemiluminescence being emitted. The light signal generated from each of the test regions on the biochip is detected by a Charge Coupled Device (CCD) camera in the Evidence MultiSTAT analyzer which, together with the analyzer software, is used to quantify the light output and produce results. The tests employ a qualitative reporting method. Each test sample is assayed against the provided Cut Off material of known concentration, which is used to determine the classification of the samples based on the comparison of the signal output.
The immunoassay processes are performed automatically in a self-contained and sealed biochip cartridge, which holds the biochips, the reagents, wash buffer and other fluids required for the test to be conducted.
## C Instrument Description Information:
1. Instrument Name:
Evidence MultiSTAT
2. Specimen Identification:
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Specimens are identified by means of a barcode which is read by the analyzer. Specimen identification can also be entered manually through the touchscreen.
3. Specimen Sampling and Handling:
Controls, cutoff calibrators, and patient samples must be manually pipetted into specific sample wells on the cartridge, which is then inserted manually into the analyzer.
4. Calibration:
The MultiSTAT assays employ a qualitative reporting method. Each test sample is assayed against a single Cut Off material of known concentration ('single point calibrant') which is used to determine the classification of the samples based on the comparison of the signal output between the Cut Off material and the test sample.
5. Quality Control:
A positive control is included with each MultiSTAT cartridge and users are instructed to analyze the controls with each run.
V Substantial Equivalence Information:
A Predicate Device Name(s):
PROFILE®-V MEDTOXScan® Drugs of Abuse Test System
B Predicate 510(k) Number(s):
K091454
C Comparison with Predicate(s):
| Device & Predicate Device(s): | Candidate Device K220451 | K091454 |
| --- | --- | --- |
| Device Trade Name | Evidence MultiSTAT Urine DOA MultiPlex, Evidence MultiSTAT | PROFILE®-V MEDTOXScan® Drugs of Abuse Test System |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Same | For the qualitative determination of drugs of abuse in human urine |
| Assay Type | Same | Competitive Immunoassay |
| Sample Matrix | Same | Urine |
| General Device Characteristic Differences | | |
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| Specific Analytes | Methamphetamine, Noroxycodone, Benzodiazepines, and Methadone. | Amphetamines, Barbiturates, Benzodiazepines, Cocaine, Methadone, Methamphetamine, Opiates, Phencyclidine, THC, Oxycodone, Tricyclic Antidepressants, and Propoxyphene. |
| --- | --- | --- |
VI Standards/Guidance Documents Referenced:
IEC 60601-1-2, Edition 4.0, 2014, Medical electrical equipment - Part 1-2: General requirements for basic safety and essential perform
CLSI EP12-A2, Edition 2. 2008. User Protocol for Evaluation of Qualitative Test Performance Approved Guideline
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
A precision study was conducted using drug free negative urine that was spiked with the appropriate analyte at -100%, -75%, -50%, -25%, +25%, +50%, +75%, +100%, of the cut off as well as at the cut off. The test was performed by at least two (2) operators on 4 instruments, with 40 replicates per lot. Representative data for each analyte is represented below.
Methadone
| Concentration (ng/ml) | % of Cut Off | Number of determinations | Results | | % Agreement |
| --- | --- | --- | --- | --- | --- |
| | | | Negative | Positive | |
| 0 | -100% | 40 | 40 | 0 | 100 |
| 75 | -75% | 40 | 40 | 0 | 100 |
| 150 | -50% | 40 | 40 | 0 | 100 |
| 225 | -25% | 40 | 40 | 0 | 100 |
| 300 | Cut Off | 40 | 1 | 39 | n/a |
| 375 | + 25% | 40 | 0 | 40 | 100 |
| 450 | +50% | 40 | 0 | 40 | 100 |
| 525 | +75% | 40 | 0 | 40 | 100 |
| 600 | +100% | 40 | 0 | 40 | 100 |
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Benzodiazepines I
| Concentration (ng/ml) | % of Cut Off | Number of determinations | Results | | % Agreement |
| --- | --- | --- | --- | --- | --- |
| | | | Negative | Positive | |
| 0 | -100% | 40 | 40 | 0 | 100 |
| 50 | -75% | 40 | 40 | 0 | 100 |
| 100 | -50% | 40 | 40 | 0 | 100 |
| 150 | -25% | 40 | 40 | 0 | 100 |
| 200 | Cut Off | 40 | 20 | 20 | n/a |
| 250 | + 25% | 40 | 2 | 38 | 95 |
| 300 | +50% | 40 | 0 | 40 | 100 |
| 350 | +75% | 40 | 0 | 40 | 100 |
| 400 | +100% | 40 | 0 | 40 | 100 |
Methamphetamine
| Concentration (ng/ml) | % of Cut Off | Number of determinations | Results | | % Agreement |
| --- | --- | --- | --- | --- | --- |
| | | | Negative | Positive | |
| 0 | -100% | 40 | 40 | 0 | 100 |
| 125 | -75% | 40 | 40 | 0 | 100 |
| 250 | -50% | 40 | 40 | 0 | 100 |
| 375 | -25% | 40 | 38 | 2 | 95 |
| 500 | Cut Off | 40 | 2 | 38 | n/a |
| 625 | + 25% | 40 | 0 | 40 | 100 |
| 750 | +50% | 40 | 0 | 40 | 100 |
| 875 | +75% | 40 | 0 | 40 | 100 |
| 1000 | +100% | 40 | 0 | 40 | 100 |
Noroxycodone
| Concentration (ng/ml) | % of Cut Off | Number of determinations | Results | | % Agreement |
| --- | --- | --- | --- | --- | --- |
| | | | Negative | Positive | |
| 0 | -100% | 40 | 40 | 0 | 100 |
| 25 | -75% | 40 | 40 | 0 | 100 |
| 50 | -50% | 40 | 40 | 0 | 100 |
| 75 | -25% | 40 | 40 | 0 | 100 |
| 100 | Cut Off | 40 | 0 | 40 | n/a |
| 125 | + 25% | 40 | 0 | 40 | 100 |
| 150 | +50% | 40 | 0 | 40 | 100 |
| 175 | +75% | 40 | 0 | 40 | 100 |
| 200 | +100% | 40 | 0 | 40 | 100 |
2. Linearity:
Not applicable. These devices are intended for qualitative use only.
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3. Analytical Specificity/Interference:
The sponsor performed a study to evaluate potential interference from various endogenous and exogenous compounds.
Using drug free negative urine two spiked samples were prepared, one at -50% of the Cut Off and one at +50% of the Cut Off. These samples were then divided into two portions where half was spiked with the interferent (test) and the other half was spiked with the same volume of matrix as a control. For each interferent there were four samples:
- Cut Off -50% spiked with Blank (Control)
- Cut Off -50% spiked with Interferent (TEST)
- Cut Off +50% spiked with Blank (Control)
- Cut Off +50% spiked with Interferent (TEST)
Results were as follows:
Methamphetamine
| Compound | Test Concentration |
| --- | --- |
| Acetone | 1000 mg/dL |
| Ethanol | 1000 mg/dL |
| Glucose | 3000 mg/dL |
| Oxalic Acid | 100 mg/dL |
| Sodium Chloride | 6000 mg/dL |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dL |
| Galactose | 10 mg/dL |
| Hemoglobin | 300 mg/dL |
| Riboflavin | 7.5 mg/dL |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dL |
| Human Serum Albumin | 500 mg/dL |
| Urea | 3500 mg/dL |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Promethazine HCl | 500,000 ng/mL |
| Phenothiazine | 50,000 ng/mL |
| Atomoxetine HCl | 500,000 ng/mL |
| (±)-Propranolol hydrochloride | 100,000 ng/mL |
| Trifluoperazine diHCl | 125,000 ng/mL |
| Dopamine HCl | 500,000 ng/mL |
| Bupropion HCl | 500,000 ng/mL |
| Oxazepam | 500,000 ng/mL |
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| Compound | Test Concentration |
| --- | --- |
| Valproic acid sodium salt | 500,000 ng/mL |
| Phenobarbital | 500,000 ng/mL |
| (±)-Methadone HCl | 500,000 ng/mL |
| Codeine Monohydrate | 500,000 ng/mL |
| Sertraline HCl | 125,000 ng/mL |
| Chlorpromazine HCl | 500,000 ng/mL |
| Doxepin Hydrochloride | 200,000 ng/mL |
| Benzoylecgonine Tetrahydrate | 500,000 ng/mL |
| Morphine Sulfate Salt Pentahydrate | 500,000 ng/mL |
| Trazodone HCl | 500,000 ng/mL |
| Dextromethorphan hydrobromide monohydrate | 500,000 ng/mL |
| Scopolamine Hydrobromide | 250,000 ng/mL |
| Thioridazine | 250,000 ng/mL |
| Brompheniramine Maleate | 250,000 ng/mL |
| Chlorpheniramine | 500,000 ng/mL |
| Methapyrilene | 100,0000 ng/mL |
| Pethidine HCl (Meperidine Hydrochloride) | 500,000 ng/mL |
| Dextropropoxyphene | 500,000 ng/mL |
| Procainamide HCl | 100,000 ng/mL |
| Buspirone HCl | 125,000 ng/mL |
| Triflupromazine HCl | 125,000 ng/mL |
| Secobarbital | 100,000 ng/mL |
| Methaqualone | 500,000 ng/mL |
| Phencyclidine | 500,000 ng/mL |
| Amobarbital | 500,000 ng/mL |
| Lorazepam | 50,000 ng/mL |
| Fentanyl | 50,000 ng/mL |
| Noroxycodone | 50,000 ng/mL |
| Tramadol | 50,000 ng/mL |
| Norbuprenorphine | 50,000 ng/mL |
| 6-Acetylmorphine | 50,000 ng/mL |
| (-)-11-nor-9-Carboxy-Δ9-THC | 50,000 ng/mL |
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Noroxycodone
| Compound | Test Concentration |
| --- | --- |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Promethazine HCl | 500,000 ng/ml |
| (-) Nicotine | 500,000 ng/ml |
| (±)-Propranolol hydrochloride | 250,000 ng/ml |
| Bupropion HCl | 500,000 ng/ml |
| (1S,2R)-(+)-Ephedrine | 500,000 ng/ml |
| Valproic acid sodium salt | 500,000 ng/ml |
| (+)-Methadone Hydrochloride | 500,000 ng/ml |
| Tyramine | 500,000 ng/ml |
| Chlorpromazine HCl | 500,000 ng/ml |
| Benzoylecgonine Tetrahydrate | 500,000 ng/ml |
| Trazodone HCl | 500,000 ng/ml |
| Brompheniramine Maleate | 250,000 ng/ml |
| Chlorpheniramine | 500,000 ng/ml |
| (+)-Norpropoxyphene | 100,000 ng/ml |
| Ecgonine Methyl Ester | 500,000 ng/ml |
| Pethidine HCl (Meperidine HCl) | 500,000 ng/ml |
| Phenylpropanolamine | 250,000 ng/mL |
| Phencyclidine | 500,000 ng/ml |
| Secobarbital | 100,000 ng/ml |
| Amobarbital | 100,000 ng/ml |
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Benzodiazepines I
| Compound | Test Concentration |
| --- | --- |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.9 mg/ml |
| Sodium Fluoride | 10 g/l |
| Procaine HCl | 100,000 ng/ml |
| Furosemide | 100,000 ng/ml |
| Sodium Azide | 10 mg/ml |
| Boric Acid | 10 mg/ml |
| (1S,2R)-(+)-Ephedrine | 500,000 ng/ml |
| (1R,2R)-(-)-Pseudoephedrine | 100,000 ng/ml |
| (1S, 2S)-(+)-Pseudoephedrine | 100,000 ng/ml |
| (-)-alpha-Acetylmethadol HCl | 100,000 ng/ml |
| Chloramphenicol | 100,000 ng/ml |
| Labetalol HCl | 100,000 ng/ml |
| Atropine Sulfate | 100,000 ng/ml |
| (±)-Methadone Hydrochloride | 500,000 ng/ml |
| (+) - Methamphetamine Hydrochloride | 500,000 ng/ml |
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| Bilirubin | 0.15 mg/ml |
| --- | --- |
| Codeine Monohydrate | 500,000 ng/ml |
| MDEA HCl | 500,000 ng/ml |
| Quinidine | 100,000 ng/ml |
| (-)-isoproterenol HCl | 100,000 ng/ml |
| (-)-Cotinine | 100,000 ng/ml |
| Cocaine Hydrochloride | 500,000 ng/ml |
| Benzoylecgonine Tetrahydrate | 500,000 ng/ml |
| Morphine Sulfate Salt Pentahydrate | 500,000 ng/ml |
| (-)-11-Nor-Δ9-THC Carboxylic Acid | 500,000 ng/ml |
| Aspartame | 100,000 ng/ml |
| Benzilic Acid | 100,000 ng/ml |
| Estrone | 100,000 ng/ml |
| Chlorpheniramine | 500,000 ng/ml |
| EDDP Perchlorate | 100,000 ng/ml |
| Loperamide Hydrochloride | 100,000 ng/ml |
| Pentobarbital | 500,000 ng/ml |
| Oxycodone Hydrochloride | 100,000 ng/ml |
| Heroin | 100,000 ng/ml |
| Chloroquine | 100,000 ng/ml |
| Ecgonine Methyl Ester | 500,000 ng/ml |
| Ketamine HCl | 100,000 ng/ml |
| (-) 11-Hydroxy-delta9-THC | 100,000 ng/ml |
| (±)-MDMA | 100,000 ng/ml |
| PCP | 100,000 ng/ml |
| 6MAM | 100,000 ng/ml |
| (±)-MDA | 100,000 ng/ml |
| Amitriptyline HCl | 125,000 ng/ml |
| (±) MBDB | 100,000 ng/ml |
| Cannabidiol | 100,000 ng/ml |
| EMDP | 100,000 ng/ml |
| Secobarbital | 100,000 ng/ml |
| d,l-Amphetamine-D5 HCl | 100,000 ng/ml |
| Amobarbital | 100,000 ng/ml |
| (-)-Δ9-THC | 100,000 ng/ml |
| Dihydrocodeine | 100,000 ng/ml |
| Cocaethylene (Benzoylecgonine ethyl ester) | 100,000 ng/ml |
| Perphenazine | 100,000 ng/ml |
| Phenethylamine | 100,000 ng/ml |
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Methadone
| Compound | Test Concentration |
| --- | --- |
| Acetone | 1000 mg/dl |
| Ethanol | 1000 mg/dl |
| Glucose | 3000 mg/dl |
| Oxalic Acid | 100 mg/dl |
| Sodium Chloride | 6000 mg/dl |
| Caffeine | 1 mg/ml |
| Ascorbic Acid | 1500 mg/dl |
| Galactose | 10 mg/dl |
| Hemoglobin | 300 mg/dl |
| Riboflavin | 7.5 mg/dl |
| Acetaminophen | 1 mg/ml |
| Ibuprofen | 1 mg/ml |
| Creatinine | 5 mg/ml |
| Gamma Globulin | 500 mg/dl |
| Human Serum Albumin | 500 mg/dl |
| Urea | 3500 mg/dl |
| Acetylsalicylic Acid | 1 mg/ml |
| Ranitidine | 0.1 mg/ml |
| Salbutamol | 100,000 ng/ml |
| Sodium Fluoride | 10 g/l |
| (±) Metoprolol (+)Tartrate | 100,000 ng/ml |
| Lisinopril | 100,000 ng/ml |
| Imipramine HCl | 100,000 ng/ml |
| (-) Nicotine | 500,000 ng/ml |
| Quetiapine Fumarate | 100,000 ng/ml |
| (S)- Duloxetine HCl | 100,000 ng/ml |
| Omeprazole | 100,000 ng/ml |
| Loratadine | 100,000 ng/ml |
| Carbamazepine | 100,000 ng/ml |
| Fluoxetine HCl | 100,000 ng/ml |
| Metformin hydrochloride | 100,000 ng/ml |
| Nortriptyline HCl | 100,000 ng/ml |
| Sodium Azide | 10 mg/ml |
| Boric Acid | 10 mg/ml |
| Bupropion HCl | 500,000 ng/ml |
| Diphenhydramine | 50,000 ng/ml |
| Oxazepam | 500,000 ng/ml |
| Tramadol HCl | 100,000 ng/ml |
| (1S, 2S)-(+)- | 100,000 ng/ml |
| Gabapentin | 100,000 ng/ml |
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| Phenobarbital | 500,000 ng/ml |
| --- | --- |
| Cetirizine Dihychloride | 100,000 ng/ml |
| (+) - Methamphetamine | 500,000 ng/ml |
| Zolpidem | 100,000 ng/ml |
| Citric Acid | 8 mg/ml |
| Potassium Chloride | 60 mg/ml |
| Bilirubin | 0.15 mg/ml |
| Codeine Monohydrate | 100,000 ng/ml |
| MDEA HCl | 500,000 ng/ml |
| Hydromorphone HCl | 100,000 ng/ml |
| Sertraline HCl | 125,000 ng/ml |
| L-Thyroxine | 100,000 ng/ml |
| Chlorpromazine HCl | 100,000 ng/ml |
| Clomipromine | 50,000 ng/ml |
| Desipramine | 100,000 ng/ml |
| Benzoylecgonine | 500,000 ng/ml |
| Morphine Sulfate Salt | 500,000 ng/ml |
| Pentahydrate | |
| Hydrocodone | 50,000 ng/ml |
| (-)-11-Nor-Δ9-THC | 500,000 ng/ml |
| Carboxylic Acid | |
| Amlodipine besylate | 100,000 ng/ml |
| Amoxicillin Trihydrate | 500,000 ng/ml |
| Atorvastatin Calcium Salt | 100,000 ng/ml |
| Compound Losartan | 100,000 ng/ml |
| Chlorpheniramine | 50,000 ng/ml |
| D-(+)-Amphetamine | 500,000 ng/ml |
| Buprenorphine | 500,000 ng/ml |
| Oxycodone Hydrochloride | 100,000 ng/ml |
| Fluphenazine | 100,000 ng/ml |
| Calcium Chloride | 3 mg/ml |
| Sodium Phosphate | 3 mg/ml |
| DL β-Hydroxybutyric | 1 mg/ml |
| Uric Acid | 100,000 ng/ml |
| Fentanyl | 100,000 ng/ml |
| Pethidine HCl
(Meperidine Hydrochloride) | 25,000 ng/ml |
| Oxymorphone | 100,000 ng/ml |
| (±)-MDMA | 100,000 ng/ml |
| 6MAM | 100,000 ng/ml |
| (±)-MDA | 100,000 ng/ml |
| Amitriptyline HCl | 25,000 ng/ml |
{14}
No interference was seen for any of the assays except for Ranitidine with the methadone assay. The sponsor repeated the study with lower amounts of ranitidine and found that the highest concentration that did not interfere with the methadone assay was 0.1 mg/mL.
The sponsor performed a study to determine if the specific gravity of the samples interfered with the results. The Specific Gravity of drug free negative urine aliquots was adjusted to a range from 1.000 to 1.030. For each Specific Gravity (sG) level two spiked samples were prepared, one at -50% of the Cut Off and one at +50% of the Cut Off. No positive or negative interference was seen with any of the assays at the specific gravities tested.
The sponsor also performed a study to determine if the pH of the samples interfered with the results. The pH of drug free negative urine aliquots was adjusted to a pH range of 3 to 11. For each pH level two spiked samples were prepared, one at -50% of the Cut Off and one at +50% of the Cut Off. No positive or negative interference was seen with any of the assays at the pH levels tested.
The sponsor also performed a study to determine the cross-reactivity from structurally related compounds by identifying the concentration of a compound prepared in drug free negative urine that would produce a positive response for each assay when analysed against the cut off material. The results are summarized below.
Methadone
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| (±)-Methadone | 300 | 100.0 |
| EDDP Perchlorate | Negative at 30,000 ng/ml | Not Detected |
| EMDP | Negative at 100,000 ng/ml | Not Detected |
| (-)-alpha-Acetylmethadol HCl (LAAM HCl) | Negative at 500,000 ng/mL | Not Detected |
| α-Noracetylmethadol (Nor-LAAM) | 500,000 ng/mL | 0.6 |
| α-Methadol | 30,000 ng/mL | 1.0 |
| Isomethadone | 50,000 ng/mL | 0.6 |
K220451 - Page 15 of 22
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Benzodiazepines 1
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| Oxazepam | 200 | 100.0 |
| Alprazolam | 35 | 571.4 |
| Flubromazolam | 50 | 400.0 |
| Flualprazolam | 60 | 333.3 |
| Nordiazepam | 110 | 181.8 |
| Diazepam | 150 | 133.3 |
| Midazolam | 190 | 105.3 |
| Desalkylflurazepam | 200 | 100.0 |
| Flubromazepam | 200 | 100.0 |
| Clobazam | 300 | 66.7 |
| Pyrazolam | 300 | 66.7 |
| Bromazepam | 360 | 55.6 |
| α-OH-Alprazolam | 400 | 50.0 |
| Chlordiazepoxide | 400 | 50.0 |
| Temazepam | 400 | 50.0 |
| Delorazepam | 900 | 22.2 |
| Nitrazepam | 900 | 22.2 |
| α-OH-Flualprazolam | 1,000 | 20.0 |
| Flunitrazolam | 1,000 | 20.0 |
| Phenazepam | 1,200 | 16.7 |
| Lorazepam | 1,250 | 16.0 |
| Prazepam | 22,000 | 0.9 |
| Meclonazepam | 2,750 | 7.3 |
| Medazepam | 3,000 | 6.7 |
| Flunitrazepam | 3,200 | 6.3 |
| Diclazepam | 4,000 | 5.0 |
| Lormetazepam | 6,000 | 3.3 |
| Clonazepam | 8,000 | 2.5 |
K220451 - Page 16 of 22
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Methamphetamine
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| S-(+)- Methamphetamine | 500 | 100.0 |
| PMMA HCl | 400 | 125.0 |
| (±)-MDMA | 1,000 | 50.0 |
| (±)- Methamphetamine | 1,000 | 50.0 |
| (±)-MBDB | 15,000 | 3.3 |
| (±)-MDEA | 30,000 | 1.7 |
| BDB | 40,000 | 1.25 |
| DL-Fenfluramine | 75,000 | 0.7 |
| (1S,2S)-(+)- Pseudoephedrine | 120,000 | 0.4 |
| Mephedrone HCl | 125,000 | 0.4 |
| Flephedrone | 400,000 | 0.13 |
| Mephentermine HCl | 1,000,000 | 0.05 |
| (±)-Amphetamine | Negative at 50,000ng/ml | Not Detected |
| R-(-)-Amphetamine | Negative at 50,000ng/ml | Not Detected |
| S-(+)-Amphetamine | Negative at 50,000ng/ml | Not Detected |
| (±)-MDA | Negative at 50,000ng/ml | Not Detected |
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K220451 - Page 18 of 22
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| R-(-)-Methamphetamine | Negative at 100,000ng/ml | Not Detected |
| Phentermine | Negative at 50,000ng/ml | Not Detected |
| PMA HCl | Negative at 50,000ng/ml | Not Detected |
| Diphenhydramine | Negative at 100,000ng/ml | Not Detected |
| (1R,2R)-(-)-Pseudoephedrine | Negative at 500,000ng/ml | Not Detected |
| (1S,2R)-(+)-Ephedrine HCl | Negative at 500,000ng/ml | Not Detected |
| Phenylephrine | Negative at 300,000ng/ml | Not Detected |
| Tyramine | Negative at 400,000ng/ml | Not Detected |
| Atomoxetine HCl | Negative at 500,000ng/ml | Not Detected |
| 4-Methyl-2- Hexylamine HCl (DMAA HCl) | Negative at 500,000ng/ml | Not Detected |
| Dopamine HCl | Negative at 500,000ng/ml | Not Detected |
| Isoxsuprine HCl | Negative at 500,000ng/ml | Not Detected |
| Phenmetrazine HCl | Negative at 100,000ng/ml | Not Detected |
| Tranylcypromine HCl | Negative at 50,000ng/ml | Not Detected |
| Phenethylamine | Negative at 100,000ng/ml | Not Detected |
| Benzphetamine | Negative at 500,000ng/ml | Not Detected |
| Phenylpropanolamine | Negative at 100,000ng/ml | Not Detected |
Noroxycodone
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| Noroxycodone | 100 | 100.0 |
| Noroxymorphone | 1000 | 11.96 |
| Dextromethorphan | Negative at 1,000,000 ng/mL | Not Detected |
| Hydrocodone | 40 | 250.0 |
| Oxycodone | 70 | 142.9 |
| Norhydrocodone | 100 | 100.0 |
| Norcodeine | 20,000 | 0.5 |
{18}
| Compound | Approximate Concentration to Read Positive (ng/ml) | Approximate % Cross Reactivity |
| --- | --- | --- |
| Naloxone | 50,000 | 0.2 |
| 6-Acetylcodeine | Negative at 10,000 ng/ml | Not Detected |
| 6-Acetylmorphine | Negative at 50,000 ng/ml | Not Detected |
| Codeine | 15,000 | 0.67 |
| Codeine glucuronide | Negative at 100,000 ng/ml | Not detected |
| Desomorphine | Negative at 10,000 ng/ml | Not Detected |
| Dihydrocodeine | Negative at 10,000 ng/ml | Not Detected |
| Ethyl Morphine | Negative at 10,000 ng/ml | Not Detected |
| Heroin | Negative at 10,000 ng/ml | Not Detected |
| Hydromorphone | Negative at 15,000 ng/ml | Not Detected |
| Levorphanol Tartrate | Negative at 10,000 ng/ml | Not Detected |
| Morphine | Negative at 50,000 ng/ml | Not Detected |
| Morphine-3βD-Glucuronide | Negative at 10,000 ng/ml | Not Detected |
| Morphine-6βD-Glucuronide | Negative at 10,000 ng/ml | Not Detected |
| Normorphine | Negative at 10,000 ng/ml | Not Detected |
| Oxymorphone | Negative at 30,000 ng/ml | Not Detected |
| Norbuprenorphine | Negative at 100.000 ng/mL | Not Detected |
| Oxymorphone Glucuronide | Negative at 30,000 ng/ml | Not Detected |
| Thebaine | Negative at 10,000 ng/ml | Not Detected |
4. Assay Reportable Range:
Not applicable. The assays are qualitative and reported as positive or negative.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
K220451 - Page 19 of 22
{19}
The assays are traceable to commercially available standards.
6. Detection Limit:
Not applicable. The assays are qualitative and reported as positive or negative.
7. Assay Cut-Off:
See section VII.A.1 above for a description of how the device performs around the cutoffs.
8. Accuracy (Instrument):
Not applicable
9. Carry-Over:
All components of the assay that contact the urine sample are single use and disposable. Therefore, carryover from one sample to another is not applicable.
B Comparison Studies:
1. Method Comparison with Predicate Device:
A method comparison study was conducted using clinical samples tested on the Randox Evidence MultiSTAT DOA Urine Multi-Plex and compared to results from a chemically specific quantitative comparator method. Results are summarized below.
Methamphetamine (n=137)
| | LC/MS/MS | | | |
| --- | --- | --- | --- | --- |
| MultiSTAT Result c/o = 500 ng/ml | Low Negative Less than 50% below the c/o (<250 ng/ml) | Near Cut Off Negative Between 50% below the c/o and the c/o (250 – 500 ng/ml) | Near Cut Off Positive Between 50% above the c/o and the c/o (500 – 750 ng/ml) | High Positive Greater than 50% above the c/o (>750 ng/ml) |
| Positive | 2* | 3 | 4 | 57 |
| Negative | 65 | 6 | 0 | 0 |
*these samples contained one or more of the following cross-reactants that contributed to the positive result: Pseudoephedrine and MDMA.
K220451 - Page 20 of 22
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Noroxycodone (n=80)
| | LC/MS/MS | | | |
| --- | --- | --- | --- | --- |
| MultiSTAT Result c/o = 100 ng/ml | Low Negative
Less than 50% below the c/o (<50 ng/ml) | Near Cut Off Negative
Between 50% below the c/o and the c/o (50 – 100 ng/ml) | Near Cut Off Positive
Between 50% above the c/o and the c/o (100 – 150 ng/ml) | High Positive
Greater than 50% above the c/o (>150 ng/ml) |
| Positive | 11* | 5* | 4 | 36 |
| Negative | 21 | 3 | 0 | 0 |
*these samples contained one or more of the following cross-reactants that contributed to the positive result: Codeine, Hydrocodone, Norhydrocodone, and Oxycodone.
Benzodiazepines 1 (n=133)
| | LC/MS/MS | | | |
| --- | --- | --- | --- | --- |
| MultiSTAT Result c/o = 200 ng/ml | Low Negative
Less than 50% below the c/o (<100 ng/ml) | Near Cut Off Negative
Between 50% below the c/o and the c/o (100 – 200 ng/mL) | Near Cut Off Positive
Between 50% above the c/o and the c/o (200 – 300 ng/ml) | High Positive
Greater than 50% above the c/o (>300 ng/ml) |
| Positive | 0 | 5* | 11 | 34 |
| Negative | 72 | 10 | 1 | 0 |
*these samples contained one or more of the following cross-reactants that contributed to the positive result: alpha-OH- Alprazolam and Temazepam.
Methadone (n=287)
| | LC/MS/MS | | | |
| --- | --- | --- | --- | --- |
| MultiSTAT Result c/o = 300 ng/ml | Low Negative
Less than 50% below the c/o (<150 ng/ml) | Near Cut Off Negative
Between 50% below the c/o and the c/o (150 – 300 ng/ml) | Near Cut Off Positive
Between 50% above the c/o and the c/o (300 – 450 ng/ml) | High Positive
Greater than 50% above the c/o (>450 ng/ml) |
| Positive | 0 | 2 | 4 | 40 |
| Negative | 229 | 12 | 0 | 0 |
K220451 - Page 21 of 22
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2. **Matrix Comparison:**
Not applicable. Only urine samples may be used with the candidate device.
**C Clinical Studies:**
1. **Clinical Sensitivity:**
Not applicable.
2. **Clinical Specificity:**
Not applicable.
3. **Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):**
Not applicable.
**D Clinical Cut-Off:**
Not applicable.
**E Expected Values/Reference Range:**
Not applicable.
**F Other Supportive Instrument Performance Characteristics Data:**
Not applicable.
**VIII Proposed Labeling:**
The labeling supports the finding of substantial equivalence for this device.
**IX Conclusion:**
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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