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   Shore, another question...drug tests this time (Pain Management board)

25th February 2005
Just thought i would pop in as I have had one drug test done at my pain clinic.They can and do check for very specific types of meds.They hit on all the top opiates,oxycodone,hydro,.....and they also test for marijuana,cocaine and the rest of the most popular abused illegal drugs.My test was specific in that it stated I had a large amount of oxy which was normal as I take oxy based meds.But they are pretty much specific as to what they are looking for and how much you have in your system.i only have had to have the one test so far and it has been about a year now.i know when you first start with them, they do kind of a baseline test after a couple of weeks to make sure that you indeed are taking the Rxed meds and not diverting them.And of course to check for any drugs that you may be doing that you are not supposed to be doing.Hope this helped.Marcia
27th February 2005
This is what I have found.
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.
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Only when this test is done for exclusion of employment or termination of employment would a lab need to do the confirmation with GC-MS to prevent a law suit for wrongful terminination for not doing the confirmation with GC-MS


As long as you haven't diluted your urine beyond 300ng per ml of urine. "300 nanograms per ML" Which wouldn't be hard to do, People have been fooling UA's for years simply by flushing their system and guzzling water. IF the UA doesn't show oxy in your system in a case of patient compliance, then a GS-MS test needs to be preformed to confirm the presumptive UA. I would bet thousands of people have lost their jobs or been denied employment without confirming the presumptive test due to the cost of the GS-MS testing procedure.


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.


Continued on next post, Shore
PS. If you have to take a test be able to ask what version your having done and will it be confirmed with GC-MS whch I highly doubt your insurance is going to pay for forensic testing of urine via GC-MS to simply detect abuse or diversion.
27th February 2005
Hey Trow, Acurately detecting Oxy requires the right test, not just a standard 5 panel or 7 panel UA, A test that detetcts the metabolites from morphine, Heroin and codien won't neccesarrily detect Oxycodone, particularly at lower doses where paramter ranges haven't been met . The most acuarate will test down to 150ng per ml of urine but that still excludes lower dose patients.

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.

Explain you understand why he would want you 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.

I've seen a number of posts where oxyC patients claimed to have flase nagatives, this is very possible depending on te type of test wthey performed and the dose your presently taking. IF your dose doesn't meet the minimum range reqired for a positive you could get a false negative test.
I havn't had to deal with testing for drugs in my system. I doubt with the minimal amount of Intrathecal meds delivered I would produce positive opiate results on a standard UA. IT meds don't run through your body systemically and are delivered in such minute amounts untill I'm tested I wouldn't really know what they would find, But if I were a betting man I would assume they would find nothing at all, not even the morphine that can be confirmed by a printout from the pump itself. But if the Canadain health ministry and the US armed services are aware of a testing problem and a false ngative problem I would save these articles just in case you find yourself being told their was no Oxy in your system. Most docs don't know what test is being done or the labs capabilities to test, which one they use, what the paramaters are and what the possibility of a flase negative are.

Good luck, Dave
27th February 2005
Hey Trow, 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 all.
Take care, Dave
28th February 2005
I think I might have worded that wrong. People are more likely to have a false neagtive when actively lookng for oxycodone. False positive m,eans there other substances that resemble drugs looked for. When specfically looking for a drug, if the right test isn't done you can have a false negative which can end some relationships with the PM doc.

If they arew going to test, they hav to use the right test. if something as important as continued care sis at stake, then I would like to think that initial findings were confirmed, but the cost of running GC/MS on pee tests would be outragosus and I would bet it wouldn't be done. Why would your health insurance pay for an expensive forensic test? There were a couple tests that were able to detect Oxy but does the doc know which test is being used or the lab they send it too know the reliability of each test on specific drugs, or do you just get the version they happen to use.

Higher dose patients may not have problems meeting the parts per ml in urine to call it a positive but lower dose patients, whatever that dose is that's needed to create results in the 150ng to 300ng/ per ml, of oxy or it's metabolites.

There are alot of variables so a false negative from someone that's actually taking it is very possible and well recognized by the army and the canadian health ministry.

I would save that info or remeber it's here in case you take oxy and nhave to test for it.

I use roxicodone for BT pain and may go a day or 2 without or using only 15mgs. After a few good days I wouldn't test possitive for oxy on several comercial tests and may not test possitive on anything except GC/MS due to he amount in my system. I'm a little concerned , but with the pump it's kind of hard to divert meds. ;) So I hope the relationship I have with my docs would prevail over the need to show you have tested some of your patiets.

Absolutely PM docs and clinics are going to be more closely watched for compliance of patients and compliance of docs to have measures in place, like PM contracts and the "threat of UA's." I was tested before I was admitted to their program and have been at several other PM clinics and programs I attended, even the ones that didn't use opiates were looking to see if you were using something.
Take care, Dave
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