Frequently Asked Questions: Opiate Dependency and Methadone Maintenance Treatment program follow-up

Transcription

1 Frequently Asked Questions: Opiate Dependency and Methadone Maintenance Treatment program follow-up Dr. Bhushan M. Kapur Associate Professor Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON CPSO 15nov13 Tables Table 1: Impact of half-life Amount of drug left in the body Amount of drug eliminated Start 100% 0% End of 1 st half-life End of 2 nd half-life End of 3 rd half-life End of 4 th half-life End of 5 th half-life End of 6 th half-life End of 7 th half-life 50.0% 25.0% 12.5% 6.25% 3.125% 1.56% 0.78% 50.0% 75.0% 87.5% 93.75% 96.87% 98.44% 99.22% Caution: Half-life can often be misleading. The duration of detection is dependent on amount taken larger the amount taken longer is the detection period going to be. Sensitivity of the analytical method more sensitive the method the longer is the detection period. Table 2: Poppy seed Bagel and Immunoassay Seven volunteers ate poppy seed covered bagel (one each). Urine was collected and tested for opiates by using immunoassay (CEDIA) method on a Hitachi 717 analyser followed by Remedi-HS HPLC. Male, 30, 140lbs M, 40, 200lbs M, 50, 160 lbs. M, 40, 165 lbs. F, 40, 125 lbs. F, 25, 105 lbs. F, 35, 135 lbs. Before bagel hours post > h post Bedtime 12h post NA NA First morning void Na h post Following morning 48 h post * ng/ml. Positive >300 ng/ml. Three of the highest concentrations were subjected to HPLC screen and were negative for any opioids Bhushan Kapur All rights reserved 1

2 Table 3: Descriptive Statistics for reference ranges 1. n mean min max Std dev 95% reference range ph Cr mmol/l >2 Na Cl Bhushan Kapur et al.: Urine Fingerprinting - Detection of Sample Tampering in an Opiate Dependency Program, Ther Drug Mon, 21: , (1999). Table 4: Effects on EIA including CEDIA procedures. Summary of adulteration studies in Literature and our Lab. Amp Barb Benz Coc Opi PCP THC Marker Bicarbonate ph, Na Bleach 1% Na, Cl, Bleach 10% smell Detergent ph Drano 0.1% ph Drano 20% Golden seal tea dark color Lemon Juice ph Salt Vinegar ph Visine ? Water loading* (in-vivo) Liquid soap Na, Cl, SpGr ± ± ± ± ± ± ± Cr, SpGr cloudy ++ = strong interference; + = weak interference; - = no interference Although these interferences have been reported in literature, they are dependent on the amount added to the urine. *Water loading or in-vivo dilution is the most common form of adulteration Bhushan Kapur All rights reserved 2

3 Table 5: Drug half-lives and approximate urine detection periods Methamphetamine 12 to 34 hours 2-3 days 1) If Enzyme Immunoassay (EIA) is positive, confirmation by chromatography is required because of high incidence of false positives; Amphetamine (metabolite of methamphetamine) Methyenedioxymethamphe tamine (MDMA) (aka Ecstasy) 7-34 hours 2) EIA cross-reacts with phenylpropanolamine, ephedrine, pseudoephedrine, bromphenriamine, bupropion, tradazone, chlorpromazine, promethazine, ranitidine etc.; (see tables 6 & 6a) 7.6 hours 2 to 3 days 3) MDMA, MDA will be positive with the new generation Ecstasy EIA assay but will also cross-react with amphetamine derivatives as in (2). 4) Chromatography required in differentiating amphetamine derivatives such as MDA and MDMA. Opiates *** 1.3 to 6.7 hours Opiates positive for 2-4 days (EIA)*** 1) EIA does not differentiate between opiates, and has a poor sensitivity for oxycodone, meperidine Morphine (morphine) 2) Chromatography required in identifying specific opiates (codeine, oxycodone, hydrocodone etc (metabolite of Heroin, Codeine, Hydromorphone, hydrocodone) 3) Hydromorphone requires sample extraction modification. 4) Even one poppy seed bagel will be detected on EIA ( see table 5 below). 5) a small amount of morphine is biotransformed into hydromorphone but not to Oxymorphone About 10% of codeine is transferred to morphine in normal metobolizers. False positive reported in literature: quinolones Bhushan Kapur All rights reserved 3

4 Oxycodone 4 to 6 hours Not detected by opiate immunoassay specific assay required (now available) Fentanyl IV=2.5min, Intranasal=6.5min Transdermal 7h (3-12h) Not detected by opiate immunoassay. Specific immunoassay recently introduced 1) 33-66% of single dose eliminated in 24 hours. 2) Chromatography will identify Oxycodone and or its metabolites Large amount will give positive on some opiate immunoassays. Immunoassay recently introduced Chromatography will identify both fentanyl and nor-fentanyl Fentanyl is 80% to 85% protein bound Heroin 60 to 90 minutes minutes Not detected in urine. Positive for opiate (morphine) is indicative of probable Heroin use. 6-Mono-acetyl-morphine (MAM) 30 minutes few hours MAM: Detected by chromatography Specific immunoassay is available Phencyclidine (PCP) 7 to16 hours 2 to 3 days Positive incidences are very rare. Cocaine 0.5 to 1.5 hours few hours Cocaine not detected by EIA detected by chromatography Benzoylecgonine detected by EIA, chromatography. Benzoylecgonine (metabolite of cocaine) 5 to 7 hours 3 to 5 days δ 9 -Tetrahydrocannabinol (THC) δ 9 -Tetrahydrocannabinoic acid (marijuana metabolite in urine) 14 to 38 hours 90% fall in 1 hour (blood) much longer (60h) in chronic heavy users Few days to many weeks depending on chronicity of use i) Benzodiazepines few hours to days days -weeks (depending on half-life) Diazepam 15 to 40 hours 2 weeks or more after last chronic use of diazepam Parent drug not detected in urine Detected as Cannabinoids by EIA. False positive reported NAIDS naproxen and ibuprofen i) EIA does not differentiate between different benzodiazepines. Some short acting agents have poor sensitivity. - Oxaprozin (Daypro) can cause a false positive. - Gravol can cause false positive - sertraline can cause false positive Bhushan Kapur All rights reserved 4

5 ii) Clonazepam 19 to 60 hours Poor to not detected ii)extensive bio transformed, less than 0.5% excreted in urine over 24 hours sometime visible on hydrolysis and GCMS if chronic dosing is involved iii) Flunitrazepam (date rape drug Rohypnol)**** 9 to 25 hours Not differentiated by immunoassay iii) Need to test for the amino derivative of Flunitrazepam by chromatography. iv) Extensive metabolized. 2% excreted unchanged in urine iv) Bromazepam v) Lorazepam hours 9-16 hours Poor 122% cross reactivity but dosage very low Methadone 15 to 40 hours. (Lit) 1 to 4 days. In chronic users urine should always be positive EDDP (Methadone metabolite) In chronic users halflife 27+8h (BK studies) Half-life similar to methadone Barbiturate (Phenobarbital) 35 to120 hours 1 to 2 weeks after last use (Phenobarbital) Alcohol (Ethanol) Blood levels fall by an average of 3.2 to 3.9 mmol/l/hour Or 15 to18 mg/100 ml/hour in social drinkers. Can be much higher in heavy drinkers. Can be 30mg/100mL/hr (BK data) 1.5 > 12 hours depending on the peak blood level. Urine typically positive for 1 to 2 hours after BAC is zero. v) hydrolyzed urine: GCMS can differentiate between diazepam, nordiazepam, oxazepam and lorazepam At alkaline ph methadone is reabsorbed in the kidney. Chromatography or specific EIA required to distinguish methadone from its metabolite EDDP False positive reported: Diphenhydramine, Phenylpropanolamine, clomipramine, chlorpromazine, quetiapine and thioridazine, verapamil EDDP not affected by urine ph (better marker for compliance monitoring) Chromatography required to differentiate between various barbiturates False positive reported NAIDS naproxen and ibuprofen 1. During absorption phase urine level lags behind blood level i.e. BAC is higher than UAlc. 2. During elimination phase blood levels lags behind urine level i.e. UAlc is higher than BAC Bhushan Kapur All rights reserved 5

6 # Ethyl Glucuronide 2 to 3 hours Depends on use. Lit. reports up to 120h if LCMSMS (0.1mg/L) is used h (by EIA - BK data) Gamma-Hydroxybutyrate (GHB) (date rape drug) 0.02% of ethanol is excreted as ETG. 0.3 to 1.0 hour Less than 12 hours Chromatography required. Detected as GHB lactone EIA Enzyme immunoassay * R.C. Baselt: Disposition of Toxic Drugs and Chemicals in Man, Fifth Edition 2000 ** The detection period is very much dose and half-life dependent. The larger the dose, the longer the period the drug/metabolite can be detected in the urine. *** Opiates may be positive for up to 2 weeks after last use with slow release opiates. **** Flunitrazepam (Rohypnol) is usually not detected with the generic EIA benzodiazepine procedure. Use chromatography to detect Amino-Flunitrazepam Bhushan Kapur All rights reserved 6

7 Figure 6: Specific Gravity - Ur Creatinine Figure 7: Urine Temperature Kapur Seconds Temperature Regression Bhushan Kapur All rights reserved 7