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    Old 11-02-2005, 01:07 PM   #1
    kebba
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    Toxicology Negative...How?

    Hi,

    My primary doctor has prescribed 50 percocet per week for approximately two months due to lower abdomen pain. I am seeing an endo specialist on Nov 15th and he has been prescribing the meds until I find out what is happening with the specialist.

    This week I called a day early becasuse I was going to be going right by his office on my way to get my son. I told the nurse that as well. My doc ordered a toxicology urine test, and it came back negative. I had taken 2 percocets in the morning (around 7) and had the test at 3ish.

    He will not prescribe me any more because of this. I have an appointment with him tomorrow...can anyone PLEASE help me in what to say to him. I am taking what is prescribed (and sometimes not even as much as prescribed). However, I am not abusing the meds nor am I doing anything illegal with them. I am taking them myself and every 4-6 hours as prescribed. My pain is horrible and I really need them.

    Please help me....I would appreciate any feedback that would be helpful when I go see him tomorrow.

    thanks everyone!

     
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    Old 11-02-2005, 01:20 PM   #2
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    Re: Toxicology Negative...How?

    So he refused to prescribe meds because there was no trace of the meds in your urine? Does he think you are selling them or something?

     
    Old 11-02-2005, 01:22 PM   #3
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    Re: Toxicology Negative...How?

    I think he is thinking that I took too many of them all at once...?????

    I don't know, but whatever the case may be, I didn't do anything except what I was supposed to do.

     
    Old 11-02-2005, 01:39 PM   #4
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    Re: Toxicology Negative...How?

    That is really weird... Does he normally make you take a urine test when getting the prescription refilled? It seems really unusual to me that he would requested that you do the urine test in the first place?!?

    Well, the real problem for you is why did the urine test come back clean? You need to sit down with your doctor and speak to him face to face about this. Explain tht you DID take the meds that morning. Find out what would cause the test to oome up wrong etc... Good luck! I wish I had more advice to give you. This is a very strange situation!

     
    Old 11-02-2005, 01:43 PM   #5
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    Re: Toxicology Negative...How?

    Hey Kebba: Your doc must have been suspicious because you asked for your meds early. Some doctors don't care if it's a week or a day, early is early. He was suspecious enough to order a Tox Test and it came back negative. Although it obviously was an error by the lab of some kind, it's telling your doctor that you are not taking the medication. Usually in that case or situation, the doc think right away thinks that you are selling the meds. I had that happen to me once with Oxycontin. Fortunately I had known the doctor for many years and he was my Mom and Dad's doctor before they passed away, so I told him no way was I selling and he believed me. I had just built up a tolerance and got ahead in my schedule.

    I guess what I'm telling you, is you need to convince him of the terrible pain you are really are in and there's no way you could do that and not have any for yourself. Be up front and explain to him you just could not do that, and for that matter, you couldn't even afford to sell part of them. Hopefully he'll believe you and continue to write your scripts.

    Good luck and please let us know the outcome.

     
    Old 11-02-2005, 04:37 PM   #6
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    Re: Toxicology Negative...How?

    Hi Kebba, You are about the 5th person in the last 2 years to have this problem, this explains why. I have this saved as a doc to save time for everyone that's getting hammered by inacurate or the wrong test or they aren't taking enough to reach standard minimum requirements to call a test positive.
    If you follow the links you can print the articles by the US armed services, The Candaian health ministry and the NIH that all explain the problems in Oxy testing. There are a few tests capable of detecting oxy that can be used but you still have to reach minimal levels.

    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 Canadian 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.

    --------------------------------------------------------------------------------
    Last edited by Shoreline : 08-05-2005 at 01:41 PM.

    Last edited by Shoreline; 11-02-2005 at 04:50 PM.

     
    Old 11-02-2005, 04:40 PM   #7
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    Re: Toxicology Negative...How?

    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=Testin g+oxycodone[/url]

    Good luck
    Take care, Dave

     
    Old 11-02-2005, 04:53 PM   #8
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    Re: Toxicology Negative...How?

    Shore,
    I am printing and saving this - as I am positive that there WILL come a time in each of our lives that we will need this info to prove we are taking our meds as prescribed. It is scary that you know so much more than the labs, employers, doctors and evryone else! This goes in my "KEEP!" medical folder, Thank you!!!!

    -Michelle
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    Old 11-02-2005, 05:24 PM   #9
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    Re: Toxicology Negative...How?

    As Shoreline posted in much greater detail,

    oxycodone and hydrocodone (and other synthetic and semi-synthetics) do NOT show up on a standard NIDA 5-panel screen. They must each be tested for separately.

    Kebba, please tell us what happened. I hope you were not punished.

    Wren

    Last edited by Wren9; 11-02-2005 at 05:26 PM.

     
    Old 11-02-2005, 05:53 PM   #10
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    Re: Toxicology Negative...How?

    i am curious, waht was the dosage? was it hcl or was it with tylenol? this may help ur docs motive.

     
    Old 11-03-2005, 06:47 AM   #11
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    Re: Toxicology Negative...How?

    Thanks to everyone (Shoreline very very very much!).

    The dosage is 5/325. Could sometone tell me how many of those I would need to have in my system in order to show up?

    I called the doc's office and asked what type of test they took. I was a standard urine test, but he specified to look for oxycodone (since that is what he is prescribing).

    It took a little over a day to come back from the lab.

    Shoreline (Dave)...does this sound like the test that is often erroneous?

    I am armed with all of the info you all gave me and am going to see my doc at 3:15 est. I am very nervous even though I have done absolutely nothing wrong. My boyfriend is coming with me as well and will let the doc know that he handed me the medicine and saw me take the dose on the day I had the test.

    I don't know how much more "ammunition" I need...I am just so confused and upset to think that I am being doubted.

     
    Old 11-03-2005, 07:03 AM   #12
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    Re: Toxicology Negative...How?

    Good luck with your appointment! I will be here rooting for you. This whole thing is just so messed up! Hopefully your doctor will figure out there was a problem and aplogize to you!

     
    Old 11-03-2005, 07:05 AM   #13
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    Re: Toxicology Negative...How?

    kebba,

    Two things--1) percocet contains tylenol, which is very liver toxic. Any problems with the liver can cause abdominal pain, and until they've determined what is causing the lower abdominal pain, your doc is putting you at great risk by giving you anything with tylenol. Even at therapeutic doses, tylenol can severely damage your liver if you have any underlying liver disease. Your primary care physician is an idiot--the percocet could be itself causing abdominal pain or making it worse. I'd make an appt ASAP with another doc, explain the situation, and ask for labs to be done on your liver enzymes.

    The toxicity of tylenol is one of the reasons long-acting narcotic medicines were developed and used.

    2) The drug screening lab might be civilly liable for a screwed up or wrong assay performed that directly has a negative impact on your health care. You can always call them up and remind them of this. Do you have friends, family members that can verify that you are taking your medications?

    Frankly, I'd consult with another doc, preferably in pain management. This guy sounds like an idiot.

    If you do a google search on "percocet"+"liver damage" and "percocet"+"pain management" you'll find a ton of info why percocet shouldn't be used in pain management.

    Don't be passive on this-your doctor's ignorance could be putting your health at risk besides mis-managing your pain.

    Best of luck!

     
    Old 11-03-2005, 07:23 AM   #14
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    Re: Toxicology Negative...How?

    Hi,

    The doc did do enzyme tests before prescribibg the percocet.

    He knows that the pain is from endometriosis.

    I had a total hyst 2 years ago and started to suffer again from pain in my lower left abdomen. After much rresearch I found out that it is very common for the endo to have gone elsewhere before the hyst and still able to cause pain. That is why I am going back to the doc who did my hyst. He is also a specialist in endo.

    BUT...the percocet works for the pain. Any suggestions on what else I can take?
    (if he will even give it to me)

     
    Old 11-03-2005, 09:05 AM   #15
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    Re: Toxicology Negative...How?

    Kebba: You asked for a suggestion on what else you could take. If your doc wants to stay with short acting meds, ask about Oxycodone IR HCL. It's made by Roxanne and comes in 5,15, and 30 mgs. It's just the Oxy, with no Tylenol (apap), so you have no liver involvment. A lot of pharmacies don't stock the 15 and 30's, but they can get them for you, that's why I told you makes it. It would be just like taking Percosets only you wouldn't have any Tylenol to worry about.

     
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