How to use?

Package insert for testing of any combination of the following drugs: Methamphetamine, Amphetamine, Cocaine, Morphine, Ecstasy, Barbiturates, Buprenorphine, Methadone, Marijuana and Benzodiazepines.

A rapid, one step screening test for the simultaneous, qualitative detection of Methamphetamine, Amphetamine, Cocaine, Morphine, Ecstasy, Barbiturates, Buprenorphine, Methadone, Marijuana, Benzodiazepines and the metabolites in human urine.

For in vitro diagnostic use only.

INTENDED USE

Urine based Drug tests for multiple drugs of abuse range from simple immunoassay tests to complex analytical procedures. The speed and sensitivity of immunoassays have made them the most widely accepted method to screen urine for multiple drugs of abuse.

The One Step Multi-Drug Screen Test Dip Card (Urine) is a lateral flow chromatographic immunoassay for the qualitative detection of multiple drugs, drug metabolites at the following cut-off concentrations in urine:1

This test will detect other related compounds, please refer to the Analytical Specificity table in this package insert.

This assay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

SUMMARY

METHAMPHETAMINE (MET, mAMP)

Methamphetamine is an addictive stimulant drug that strongly activates certain systems in the brain. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of Methamphetamine are greater. Methamphetamine is made in illegal laboratories and has a high potential for abuse and dependence. The drug can be taken orally, injected, or inhaled. Acute higher doses lead to enhanced stimulaDtion of the central nervous system and induce euphoria, alertness, reduced appetite, and a sense of increased energy and power. Cardiovascular responses to Methamphetamine include increased blood pressure and cardiac arrhythmias. More acute responses produce anxiety, paranoia, hallucinations, psychotic behavior, and eventually, depression and exhaustion. The effects of Methamphetamine generally last 2-4 hours and the drug has a half-life of 9-24 hours in the body. Methamphetamine is excreted in the urine as amphetamine and oxidized and delaminated derivatives. However, 10-20% of Methamphetamine is excreted unchanged. Thus, the presence of the parent compound in the urine indicates Methamphetamine use.

COCAINE (COC)

Cocaine is a potent central nervous system (CNS) stimulant and a local anesthetic. Initially, it brings about extreme energy and restlessness while gradually resulting in tremors, over-sensitivity and spasms. In large amounts, cocaine causes fever, unresponsiveness, difficulty in breathing and unconsciousness.

Cocaine is often self-administered by nasal inhalation, intravenous injection and free-base smoking. It is excreted in the urine in a short time primarily as Benzoylecgonine.1.2 Benzoylecgonine, a major metabolite of cocaine, has a longer biological half-life (5-8 hours) than cocaine (0.5-1.5 hours), and can generally be detected for 24-48 hours after cocaine exposure.2

MORPHINE (MOP)

Opiate refers to any drug that is derived from the opium poppy, including the natural products, morphine and codeine, and the semi-synthetic drugs such as heroin. Opioid is more general, referring to any drug that acts on the opioid receptor. Opioid analgesics comprise a large group of substances which control pain by depressing the central nervous system. Large doses of morphine can produce higher tolerance levels, physiological dependency in users, and may lead to substance abuse. Morphine is excreted unmetabolized, and is also the major metabolic product of codeine and heroin. Morphine is detectable in the urine for several days after an opiate dose.4

MARIJUANA (THC)

THC (D9-tetrahydrocannabinol) is the primary active ingredient in cannabinoids (marijuana). When smoked or orally administered, it produces euphoric effects. Users have impaired short term memory and slowed learning. They may also experience transient episodes of confusion and anxiety. Long term relatively heavy use may be associated with behavioral disorders. The peak effect of smoking marijuana occurs in 20-30 minutes and the duration is 90-120 minutes after one cigarette. Elevated levels of urinary metabolites are found within hours of exposure and remain detectable for 3-10 days after smoking. The main metabolite excreted in the urine is 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid (D9-THC-COOH).

BENZODIAZEPINES (BZO)

Benzodiazepines are medications that are frequently prescribed for the symptomatic treatment of anxiety and sleep disorders. They produce their effects via specific receptors involving a neurochemical called gamma aminobutyric acid (GABA). Because they are safer and more effective, Benzodiazepines have replaced barbiturates in the treatment of both anxiety and insomnia. Benzodiazepines are also used as sedatives before some surgical and medical procedures, and for the treatment of seizure disorders and alcohol withdrawal. Risk of physical dependence increases if Benzodiazepines are taken regularly (e.g., daily) for more than a few months, especially at higher than normal doses. Stopping abruptly can bring on such symptoms as trouble sleeping, gastrointestinal upset, feeling unwell, loss of appetite, sweating, trembling, weakness, anxiety and changes in perception. Only trace amounts (less than 1%) of most Benzodiazepines are excreted unaltered in the urine; most of the concentration in urine is conjugated drug. The detection period for the Benzodiazepines in the urine is 3-7 days.

AMPHETAMINE (AMP)

Amphetamine is a Schedule II controlled substance available by prescription (Dexedrine®) and is also available on the illicit market. Amphetamines are a class of potent sympathomimetic agents with therapeutic applications. They are chemically related to the human body’s natural catecholamines: epinephrine and norepinephrine. Acute higher doses lead to enhanced stimulation of the central nervous system and induce euphoria, alertness, reduced appetite, and a sense of increased energy and power. Cardiovascular responses to Amphetamines include increased blood pressure and cardiac arrhythmias. More acute responses produce anxiety, paranoia, hallucinations, and psychotic behavior. The effects of Amphetamines generally last 2-4 hours following use, and the drug has a half-life of 4-24 hours in the body. About 30% of Amphetamines are excreted in the urine in unchanged form, with the remainder as hydroxylated and deaminated derivatives.

BARBITURATES (BAR)

Barbiturates are central nervous system depressants. They are used therapeutically as sedatives, hypnotics, and anticonvulsants. Barbiturates are almost always taken orally as capsules or tablets. The effects resemble those of intoxication with alcohol. Chronic use of barbiturates leads to tolerance and physical dependence. Short acting Barbiturates taken at 400 mg/day for 2-3 months can produce a clinically significant degree of physical dependence. Withdrawal symptoms experienced during periods of drug abstinence can be severe enough to cause death. Only a small amount (less than 5%) of most Barbiturates are excreted unaltered in the urine.

The approximate detection time limits for Barbiturates are:

Short acting (e.g. Secobarbital) 100 mg PO (oral) 4.5 days

Long acting (e.g. Phenobarbital) 400 mg PO (oral) 7 days.

METHADONE (MTD)

Methadone is a narcotic analgesic prescribed for the management of moderate to severe pain and for the treatment of Morphine dependence (heroin, Vicodin, Percocet, Morphine). The pharmacology of Oral Methadone is very different from IV Methadone. Oral Methadone is partially stored in the liver for later use. IV Methadone acts more like heroin. In most states you must go to a pain clinic or a Methadone maintenance clinic to be prescribed Methadone. Methadone is a long acting pain reliever producing effects that last from twelve to forty-eight hours. Ideally, Methadone frees the client from the pressures of obtaining illegal heroin, from the dangers of injection, and from the emotional roller coaster that most opiates produce. Methadone, if taken for long periods and at large doses, can lead to a very long withdrawal period. The withdrawals from Methadone are more prolonged and troublesome than those provoked by heroin cessation, yet the substitution and phased removal of methadone is an acceptable method of detoxification for patients and therapists.

MDMA (ECSTASY)

Methylenedioxymethamphetamine (ecstasy) is a designer drug first synthesized in 1914 by a German drug company for the treatment of obesity. Those who take the drug frequently report adverse effects, such as increased muscle tension and sweating. MDMA is not clearly a stimulant, although it has, in common with amphetamine drugs, a capacity to increase blood pressure and heart rate. MDMA does produce some perceptual changes in the form of increased sensitivity to light, difficulty in focusing, and blurred vision in some users. Its mechanism of action is thought to be via release of the neurotransmitter serotonin. MDMA may also release dopamine, although the general opinion is that this is a secondary effect of the drug (Nichols and Oberlender, 1990). The most pervasive effect of MDMA, occurring in virtually all people who took a reasonable dose of the drug, was to produce a clenching of the jaws.

BUPRENORPHINE (BUP)

Buprenorphine is a semisynthetic opioid analgesic derived from thebain, a component of opium. It has a longer duration of action than morphine when indicated for the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence. Low doses buprenorphine produces sufficient agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists because of the “ceiling effect”, which means no longer continue to increase with further increases in dose when reaching a plateau at moderate doses. However, it has also been shown that Buprenorphine has abuse potential and may itself cause dependency. Subutex®, and a Buprenorphine/Naloxone combination product, Suboxone®, are the only two forms of Buprenorphine that have been approved by FDA in 2002 for use in opioid addiction treatment. Buprenorphine was rescheduled from Schedule V to Schedule III drug just before FDA approval of Suboxone and Subutex.

PRINCIPLE

The One Step Multi-Drug Screen Test Dip Card (Urine) is an immunoassay based on the principle of competitive binding. Drugs which may be present in the urine specimen compete against their respective drug conjugate for binding sites on their specific antibody.

During testing, a urine specimen migrates upward by capillary action. A drug, if present in the urine specimen below its cut-off concentration, will not saturate the binding sites of its specific antibody coated on the particles. The antibody coated particles will then be captured by the immobilized drug conjugate and a visible colored line will show up in the test line region of the specific drug strip. The colored line will not form in the test line region if the drug level is above its cut-off concentration because it will saturate all the binding sites of the antibody coated on the particles.

A drug-positive urine specimen will not generate a colored line in the specific test line region of the strip because of drug competition, while a drug-negative urine specimen or a specimen containing a drug concentration less than the cut-off will generate a line in the test line region. To serve as a procedural control, a colored line will always appear at the control line region indicating that proper volume of specimen has been added and membrane wicking has occurred.

REAGENTS

Each test line in the test panel contains mouse monoclonal antibody-coupled particles and corresponding drug-protein conjugates. A goat antibody is employed in each control line.

PRECAUTIONS

· For in vitro diagnostic use only.

· Do not use after the expiration date.

· The Test Dip Card should remain in the sealed pouch until use.

· All specimens should be considered potentially hazardous and handled in the same manner as an infectious agent.

· The used Test Dip Card should be discarded according to local regulations.

STORAGE AND STABILITY

Store as packaged in the sealed pouch either at room temperature or refrigerated (2-30°C). The Test Dip Card is stable through the expiration date printed on the sealed pouch. The Test Dip Card must remain in the sealed pouch until use. Keep away from direct sunlight, moisture and heat. DO NOT FREEZE. Do not use beyond the expiration date.

SPECIMEN COLLECTION AND PREPARATION

WHEN TO COLLECT URINE FOR THE TEST?

The minimum detection time is 2-7 hours, so you may collect urine samples 2-7 hours after suspected drug use.

HOW TO COLLECT URINE?

1. Urinate directly into the provided urine cup.

2. Open the Labeled Vial and carefully pour the urine specimens from the urine cup into the Labeled Vial. Fill the vial to about two thirds (2/3) full and tightly close the cap. This Labeled Vial urine sample is for shipping to the laboratory for confirmation testing. Make sure that the number on the Labeled Vial matches your personal Identification Number.

3. The residual urine sample in the urine cup is for your self-testing.

Specimen Storage

Urine specimens may be stored at 2-8°C for up to 48 hours prior to testing. For prolonged storage, specimens may be frozen and stored below -20°C. Frozen specimens should be thawed and mixed well before testing.

MATERIALS

Materials Provided

• 25 Test dip cards •25 Desiccant • 1 Package Insert

Materials Required But Not Provided

• Timer

DIRECTIONS FOR USE

Allow the test dip card, and urine specimen to come to room temperature [15-30°C (59-86°F)] prior to testing.

1) Remove the test dip card from the foil pouch.

2) Remove the cap from the test dip card. Label the dip card with patient or control identifications.

3) Immerse the absorbent tip into the urine sample for 10-15 seconds. Urine sample should not touch the plastic dip card.

4) Replace the cap over the absorbent tip and lay the dip card flatly on a non-absorptive clean surface.

5) Read the drug strip results at 5 minutes.

DO NOT INTERPRET RESULT AFTER 10 MINUTES.

INTERPRETATION OF RESULTS

(Please refer to the illustration above)

NEGATIVE:* Two lines appear. One red line should be in the control region (C), and another apparent red or pink line adjacent should be in the test region (Drug/T). This negative result indicates that the drug concentration is below the detectable level.

*NOTE: The shade of red in the test line region (Drug/T) will vary, but it should be considered negative whenever there is even a faint pink line.

POSITIVE: One red line appears in the control region (C). No line appears in the test region (Drug/T). This positive result indicates that the drug concentration is above the detectable level.

INVALID: Control line fails to appear. Insufficient specimen volume or incorrect procedural techniques are the most likely reasons for control line failure. Review the procedure and repeat the test using a new test panel. If the problem persists, discontinue using the lot immediately and contact your manufacturer.

Note: There is no meaning attributed to line color intensity or width.

A preliminary positive test result does not always mean a person took illegal drugs and a negative test result does not always mean a person did not take illegal drugs. There are a number of factors that influence the reliability of drug tests. Certain drugs of abuse tests are more accurate than others.

IMPORTANT: The result you obtained is called preliminary for a reason. The sample must be tested by laboratory in order to determine if a drug of abuse is actually present. Send any sample which does not give a negative result to a laboratory for further testing.

What Is A False Positive Test?

The definition of a false positive test would be an instance where a substance is identified incorrectly by One Step Multi-Drug Screen Dip Card Urine. The most common causes of a false positive test are cross reactants. Certain foods and medicines, diet plan drugs and nutritional supplements may cause a false positive test result with this product.

What Is A False Negative Test?

The definition of a false negative test is that the initial substance is present but isn’t detected by One Step Multi-Drug Screen Dip Card Urine. If the sample is diluted, or the sample is adulterated that may cause false negative result.

QUALITY CONTROL

A procedural control is included in the test. A colored line appearing in the control line region (C) is considered an internal procedural control. It confirms sufficient specimen volume, adequate membrane wicking and correct procedural technique.

LIMITATIONS

1. The One Step Multi-Drug Screen Test Dip Card (Urine) provides only a qualitative, preliminary analytical result. A secondary analytical method must be used to obtain a confirmed result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method.

2. There is a possibility that technical or procedural errors, as well as other interfering substances in the urine specimen may cause erroneous results.

3. Adulterants, such as bleach and/or alum, in urine specimens may produce erroneous results regardless of the analytical method used. If adulteration is suspected, the test should be repeated with another urine specimen.

4. A positive result does not indicate level or intoxication, administration route or concentration in urine.

5. A negative result may not necessarily indicate drug-free urine. Negative results can be obtained when drug is present but below the cut-off level of the test.

6. The test does not distinguish between drugs of abuse and certain medications.

7. A positive result might be obtained from certain foods or food supplements.

PERFORMANCE CHARACTERISTICS

Accuracy

80 clinical urine specimens were analyzed by GC-MS and by the One Step Multi-Drug Screen Test Dip Card (Urine). Each test was performed by three operators. Samples were divided by concentration into five categories: drug-free, less than half the cutoff, near cutoff negative, near cutoff positive, and high positive. Results were as follows:

A

nalytical Sensitivity

Total 150 samples equally distributed at concentrations of -50% Cut-Off; -25% Cut-Off; Cut-Off; +25% Cut-Off; +50% Cut-Off were tested using three different lots of each dip card by three different operators. Results were all positive at and above +25% Cut-off and all negative at and below -25% Cut-off for Methamphetamine, Amphetamine, Cocaine, Morphine, Ecstasy, Barbiturates, Buprenorphine, Methadone, Marijuana and Benzodiazepines. The cut-off value for the dip card is verified.

Analytical Specificity

The following table lists compounds that are positively detected in urine by the One Step Multi-Drug Screen Test Dip Card (Urine) at 5 minutes.

Precision

This study is performed 2 runs/day and lasts 25 days for each format with three lots. Three operators who don’t know the sample number system participate in the study. Each of the 3 operators tests 2 aliquots at each concentration for each lot per day (2 runs/day). A total of 50 determinations by each operator, at each concentration, were made. The results are given below:

Effect of Urinary Specific Gravity

Urine samples of normal, high, and low specific gravity from 1.000 to 1.035 were spiked with drugs at 25% below and 25% above cut-off levels respectively. The One Step Multi-Drug Screen Test Dip Card (Urine) was tested in duplicate using drug-free urine and spiked urine samples. The results demonstrate that varying ranges of urinary specific gravity do not affect the test results.

Effect of Urinary pH

The pH of an aliquot of negative urine pool is adjusted in the range of 4.00 to 9.00 in 1 pH unit increment and spiked with the target drug at 25% below and 25% above Cutoff levels. The spiked, pH-adjusted urine was tested with The One Step Multi-Drug Screen Test Dip Card (Urine). The results demonstrate that varying ranges of pH do not interfere with the performance of the test.

Cross-Reactivity

A study was conducted to determine the cross-reactivity of the test with compounds in either drug-free urine or Methamphetamine, Amphetamine, Cocaine, Morphine, Ecstasy, Barbiturates, Buprenorphine, Methadone, Marijuana and Benzodiazepines positive urine. The following compounds show no cross-reactivity when tested with the One Step Multi-Drug Screen Test Dip Card (Urine) at a concentration of 100 mg/mL.

Non Cross-Reacting Compounds

BIBLIOGRAPHY

1. Stewart DJ, Inaba T, Lucassen M, Kalow W. Clin. Pharmacol. Ther. April 1979; 25 ed: 464, 264-8.

2. Ambre J. J. Anal. Toxicol. 1985; 9:241.

3. Hawks RL, CN Chiang. Urine Testing for Drugs of Abuse. National Institute for Drug Abuse (NIDA), Research Monograph 73, 1986.

4. Tietz NW. Textbook of Clinical Chemistry. W.B. Saunders Company. 1986; 1735.

5. FDA Guidance Document: Guidance for Premarket Submission for Kits for Screening Drugs of Abuse to be Used by the Consumer, 1997.

INDEX OF SYMB