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   False negative urine test (Pain Management board)

5th August 2005
Hi Ienigma, Testing for oxycodone and other keto synthetic opiates is far more difficult than testing for your standard opiates "morphine, heroin, and codeine," for 2 reasons.
1. your dose may not reach the required 150-300 ng per ml of urine to create a positive test.
2. Most tests aren't capable of detecting oxycodone and the docs and labs aren't even aware of the problem, but the US army, the Canadaian health ministry and the NIH have recognized the problem. As of the date of this original post only 3 comercially available tests could acurately detect oxy or they would have to run your urine through GC-MS "gas chromatographic-mass spectrometer," an extremely expensive testing method reserved for forensic testing.

Here is the link to the entire article to take to your doc and show him that false negatives are a common problem for detection of oxycodone use which falsely acuses patients of diversion.
[url]http://www.iatdmct.org/oxycodone.html[/url]
This is probaly going to exceed 10,000 characters because I copied 3 different articles that pretty much all said the same thing. Your doc and the lab may not even be aware of the problems involved in proper Oxycodone testing.


Summary:
Most laboratories use commercially available immunoassays to screen for opiates in urine. They do not normally confirm presumptive positive screening tests. These immunoassays were designed to detect use of the opiates - heroin, codeine and morphine but not other opiates such as hydromorphone, hydrocodone and oxycodone, etc. Clinicians and other users of laboratory services are often unaware that opiate screening methods are unable to reliably detect oxycodone use/abuse. Because of the potent analgesic effects of oxycodone, this drug is often used in pain clinics.

In 2001, medical directors of pain management centers in Canada were concerned about oxycodone diversion, i.e. selling on the street, by some of their patients. Because of these concerns, urine drug screens were ordered in several smaller centers. Since the test results might be "negative" for oxycodone screening., individual patients could be wrongfully identified as diverting their prescription drugs to others. To resolve these concerns, urine specimens must be analyzed specifically for oxycodone by GC/MS or another robust methods in order to obtain an accurate indication of oxycodone use by these patients. Further, clinical and forensic laboratories may be unaware that one cannot adequately screen for oxycodone use by commercially available opiate immunoassays. In areas where oxycodone abuse is known or suspected, laboratories providing blood and/or urine drug screening services should alert their users about the limitations of their ability to screen for oxycodone. Thus, the emergence of oxycodone as a popular drug of abuse highlights the importance of on-going communication between the laboratory and the end users. The laboratory should update the users on the advantages and limitations of blood or urine drug testing.
Oxycodone can be extracted from biological fluids by either liquid/liquid extraction or more recently, solid phase extraction techniques. Solid phase extraction techniques utilize C18, C8, or copolymeric columns. For greater sensitivity and detection, enzymatic hydrolysis with beta-glucuronidase can be used to increase the recovery of oxycodone from biological fluids.

Methods used for the detection of 6-keto-opioids, such as oxycodone, include commercial immunoassays, thin-layer chromatography (TLC), liquid chromatography (LC), automated liquid chromatography (REMEDi), liquid chromatography-mass spectrometry (LC/MS), gas chromatography (GC), and gas chromatography-mass spectrometry (GC/MS). Despite the numerous techniques, only gas or liquid chromatography coupled with mass spectrometry is the acceptable confirmation technique for quantification of opiates - morphine and codeine ( Note - oxycodone is not currently included as one of the SAMHSA analytes ) in urine according to the Department of Health and Human Services (DHHS) guidelines for drug testing of federal employees (12).

In general, immunoassays are not well suited for the detection of 6-keto-opioids, such as oxycodone, due to the low antibody cross-reactivity of the commercial opiate kits. Cone et al. showed that each of the 6-keto-opioid compounds had concentration-dependent cross-reactivities in commercial opiate immunoassays, and each had the potential to produce positive urine screening results (13). Furthermore, Smith et al. compared several commercial immunoassays to GC-MS and demonstrated that oxycodone present in urine was detected by TDx® opiates (TDx; Abbott Laboratories) and the EMIT® d.a.u. opiate assay (EMIT; Syva) for 6-24 hrs. However, the quantitative responses from these assays expressed as ng/ml of morphine equivalents were substantially lower than GC/MS determinations (8). As a result, immunoassays are not well suited for monitoring the therapeutic use, compliance, or abuse of oxycodone. Therefore, it might be advisable to confirm any immunoassay screening tests with increased urine opiate concentrations by using a suitable chromatographic method.

Toxi-Lab ATM thin-layer chromatography (TLC) drug detection system can also be used for the detection of oxycodone in urine specimens. However, therapeutic dosages of oxycodone might be below the detection limit of this system at 1.0 mg/L in 5ml aliquots. However, Gobar et al. demonstrated that oxycodone in urine samples of pain management patients was detected by TLC and then confirmed by GC/MS with cutoff limits of 300 ng/ml for both assays (15). Furthermore, the sensitivity and specificity for both assays were 72.7 and 84.2%, respectively.

Oxycodone can also be detected and/or quantitated in biological fluids by gas chromatography with FID or NPD detection. Confirmation by GC/MS in the full scan mode shows principle peaks at m/z 315, 230, 70, 258, and 140. GC/MS utilizing selective ion monitoring (SIM) of principle ions will increase assay sensitivity so that detection limits of 10 ng/ml can be achieved. At these detection limits, therapeutic use, compliance, and oxycodone abuse can be monitored.

In GC/MS, the choice of derivatization agents is one of the most important factors in the accuracy and precision of the method. Many derivatizing agents can be used including acetic anhydride (16), bis-trimethylsilytrifluoroacetamide/trimethylsilyl (BSTFA/1% TMS) (17), heptafluorobutyric anhydride (HFBA) (17), pentafluoropropionic anhydride (PFPA) (17), and MBTFA (18). Problems encountered with some GC/MS methods include instability of derivatives, poor chromatography, unsuitable ions and abundances, incomplete derivatization, derivatization side reactions, inadequate recovery, loss during hydrolysis, extended run times, and interference or coelution of other opiates (19).

Recently, an improved GC/MS method for the simultaneous identification and quantification of opiates in urine was reported (20). In this method, methoxyamine was used after enzymatic hydrolysis to form methoxime derivatives of the keto-opiates, which were extracted using solid-phase columns and derivatized with propionic anhydride/pyridine. This method demonstrated acceptable precision, the lack of cross-interference from other opioids, short analysis time of about 6.5 min, and a small sample volume of 2.0 ml urine.

Finally, LC/MS has been used to determine the concentration of oxycodone in plasma (21). This method was selective and rapid with a analysis time of 2 min. A small sample volume of 1 ml plasma was alkalinized and extracted with 2% isoamyl alcohol in n-butyl chloride. After evaporation and reconstitution in 15% methanol-85% water containing 0.1% acetic acid, the sample was analyzed by LC/MS. The limit of quantification was 1 ng/mL., and the limit of detection, 33 pg/ml. In addition, this method was linear from 1 to 100 ng/mL. In comparison, an automated LC - REMEDi is capable of screening with a sensitivity of 150 ng/mL. However, the major problem is that oxycodone is eliminated quickly from the blood as a result of its short half-life.

Overall, the analysis and quantification of oxycodone is increasingly important as its use and abuse becomes more widespread. In addition, pharmacogenetic typing of individuals taking oxycodone may be recommended, because oxycodone is metabolized to oxymorphone by cytochrome (CYP) 450 2D6. This enzyme is polymorphic with a prevalence of three mutations *3, *4, and *5 in about 10% of the general population (22). In fact, 95% of individuals classified as poor drug metabolizers have one or more of these mutations. They are more likely to experience severe toxicity or therapeutic failure. Thus, pharmacogenomics, in the near future, might become an integral part of pain management to individualize oxycodone and other drug therapy with minimized adverse reactions.

References
1. Baselt, R.C., Disposition of Toxic Drugs and Chemicals in Man, Fifth Edition, Chemical Toxicology Institute, Foster City, CA, 2000, pp. 644-645.
5th August 2005
Laboratory Methods
Laboratory detection of morphine and codeine is performed by immunoassay. Confirmation is by gas chromatography/mass spectrometry (GC/MS).

Cutoff and Detection Post Dose
The detection limit of the initial screen is 300 ng/ml, with a sensitivity of 20 ng/ml. This is sufficient to detect heroin use for approximately 24-48 hours post dose and codeine for somewhat longer. Positives are confirmed on GC/MS at a cutoff level of 300 ng/ml.

OXYCODONE
Classification: Opiate-narcotic analgesic

Background: The milky residue collected from the opium poppy plant (opium) is the natural material from which opiate compounds are extracted or synthesized. Oxycodone is a semi-synthetic opiates derived from opium. Oxycodone, like other opiates is characterized by its analgesic properties, and the tendency for users to form a physical dependency and develop tolerance with extended use. It is a commonly prescribed analgesic taken orally, frequently in combination with acetaminophen or aspirin. OxyContin, the time-release form of oxycodone, is supplied in 80 mg doses and is often called “hillbilly heroin”. When the pills are crushed, the contents can be snorted or dissolved in water and injected. Its use as a “Club Drug” is reported as on the increase.

Street Names: Oxy; OC; hillbilly heroin

Detection in Urine: 1-3 days

Physiological Effects: Analgesia (pain relief), respiratory depression, constipation. Long time use leads to dependence and tolerance so that a dramatic increase in dose is necessary for the same analgesic effect. Tolerance begins after the initial dose but is usually significant only after the second week of chronic use. A 35 fold increase in dose may be necessary for the same effect. Withdrawal symptoms may begin 6-8 hours after the last dose and reach a peak at 36–72 hours.

Toxicity: Respiratory depression/failure is the greatest risk associated with opiate abuse aside from the risk of infection associated with illicit intravenous drug use.

Psychological Effects: Sedation, euphoria, mental clouding

Cutoff Levels: ImmunoAssay screen test: 500 ng/mL
GCMS confirmation test:
300 ng/mL


Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology, Washington, DC 20306-6000.

Opiate testing for morphine and codeine is performed routinely in forensic urine drug-testing laboratories in an effort to identify illicit opiate abusers. In addition to heroin, the 6-keto-opioids, including hydromorphone, hydrocodone, oxymorphone, and oxycodone, have high abuse liability and are self-administered by opiate abusers, but only limited information is available on detection of these compounds by current immunoassay and gas chromatographic-mass spectrometric (GC-MS) methods. In this study, single doses of hydromorphone, hydrocodone, oxymorphone, and oxycodone were administered to human subjects, and urine samples were collected before and periodically after dosing. Opiate levels were determined in a quantitative mode with four commercial immunoassays, TDx opiates (TDx), Abuscreen radioimmunoassay (ABUS), Coat-A-Count morphine in urine (CAC), and EMIT d.a.u. opiate assay (EMIT), and by GC-MS. GC-MS assay results indicated that hydromorphone, hydrocodone, oxymorphone, and oxycodone administration resulted in rapid excretion of parent drug and O-demethylated metabolites in urine. Peak concentrations occurred within 8 h after drug administration and declined below 300 ng/mL within 24-48 h. Immunoassay testing indicated that hydromorphone, hydrocodone, and oxycodone, but not oxymorphone, were detectable in urine by TDx and EMIT (300-ng/mL cutoff) for 6-24 h. ABUS detected only hydrocodone, and CAC failed to detect any of the four 6-keto-opioid analgesics. Generally, immunoassays for opiates in urine displayed substantially lower sensitivities for 6-keto-opioids compared with GC-MS. Consequently, urine samples containing low to moderate concentrations of hydromorphone, hydrocodone, oxymorphone, and oxycodone will likely go undetected when tested by conventional immunoassays.

Take in these articles and Explain you are willing to switch to a drug thats easier to detect but it's a shame to give up a med that's effective just because we presently don't have an easy and inexpensive way to detect OxyCodone in Urine.

Here is the entire post by suzie where we discussed this last year some time, after she receved a false negative on an Oxy screen done by conventional UA's.

[url]http://www.healthboards.com/boards/showthread.php?t=161204&highlight=Testing+oxycodone[/url]

Good luck
Take care, Dave
2nd April 2010
How about this. I also have showed up negative in a screening test for Oxycodone/Oxymorphone. I came up with a great idea to show my doctor that I am taking my medication as prescribed. I got the Doctor to agree to allow me to come into his office in the morning and take my Oxycontin right in front of him. Then, that afternoon (over my lunch break) I took for breakthrough (I was having some breakthrough pain while at lunch) a percocet (when I was on them) right in front of him. After work, I went to his office and I went to the bathroom in one of those testing cups. One of those cups that tells instantly when you pull back the strip. . . And WOW! . . . If only you could have seen the look on my Doctors eyes when I showed negative for Oxycodone/Oxymorphone! He said, T***, this isn't possible. I have been practicing pain medicine for 22 years, I have never seen this in my field or heard of this ever. You are the first to have ever proven me wrong. I knew I would show negative. Basically, for me, it's a hit or a miss on what I will show. I would say I show positive about every 4th test. . . The rest, well, they are always negative. I have even had a blood test done that showed negative. So, I'm in the clear with my Doctor now, who still chooses to test me. . Because he wants to make sure nothing that's not supposed to shows up in there. So, this is 100% proof that those tests don't always work for everyone. As for what I took for the medication, I had taken an Oxycontin 20mg and a Percocet 10mg in front of him.

Tbreeze27!!
2nd June 2010
well; i was taking roxycodone and was urine tested in my pm office and it showed up no problem-perhaps the test kit was flawed?
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