1. Drugs of Abuse Service: Urine and oral fluid testing Dr Paul Cawood Toxicology, Clinical Biochemistry, RIE GP-Laboratory Medicine Update Meeting 11 th February 2016

2. Drugs of Abuse

3. Mark Adley version 1.0 14/03/2014 mark@thedrugswheel.com The Drugs Wheel Training

4. Dihydrocodeine 301.4 Conjugates Heroin (Diacetyl Morphine + Acetyl Codeine) - metabolised too quickly to detect in urine 6-MonoAcetyl Morphine 327.4 Codeine 299.4 Morphine 285.3 Hydrocodone 299.4 Conjugates

5. Benzodiazepine metabolism Nordiazepam T½ 39-96h Chlordiazepoxide (librium) T½ 6-28 h Diazepam (valium) T½ 20-70 h Temazepam* T½ 8-20 h Oxazepam* T½ 5-15 h Conjugation Urinary Excretion Nitrazepam T½ 20-30 h Clonazepam T½ 18-50 h Flunitrazepam T½ 10-40 h 7-Amino metabolites Active drug

6. Urine Drugs of Abuse Move 2 years ago to specific drug analysis by Tandem MS to confirmation standard – Fully ISO accredited Currently 20 drugs: Morphine, codeine, 6MAM, DHC AMP, MDMA, MetAMP Cocaine metabolite EDDP, Methadone Diazepam, Nordiazepam, Temazepam, Oxazepam, Nitrazepam, 7-A-Clonazepam Gabapentin, Tramadol Buprenorphine, Norbuprenorphine

7. Spiked sample detection in urine Methadone strongly positive with undetected EDDP Diazepam strongly positive with undetected Nordiazepam Buprenorphine strongly positive with undetected nordiazepam Temazepam strongly positive Reported as “methadone strongly positive with undetectable EDDP is inconsistent with recent methadone consumption but is suggestive of methadone being added to (spiked into) the urine sample”

8. Liquid Chromatography - Tandem Mass Spectrometer Detector

10. Example of calibration – nordiazepam 7 point calibration curve 5-1000µg/L

11. Quantitative peak 468.3 > 55.0 Qualifying peak 468.3 > 101.0 Internal Standard 472.2 > 59.1 Drug identification: 1)Retention times match internal standard 2)Peaks are same shape 3)Ratio of quatifying:qualifying match standards

12. Requesting oral fluid Using Blood Science request form – indicating oral fluid as the sample type GP ICE – Oral fluid drugs of Abuse will be added to Common Tests screen 14 th Feb TRAK Collection devices available from Astley Ainslie Stores as a non-stock item “Sarstedt Salivette Blue: 51.1534.500” in boxes of 100.

13. Chew plug for 1 min Sample volume 50µl Clean analysis v urine Costs for urine and oral fluid are the same Can mix and match urine / Oral fluid as required Advantage of witnessed collection Mouth can be contaminated With prescribed drugs e.g. buprenorphine, diazepam Metabolites are not reliably present

15. DrugThreshold oral fluid Driving under influence of drugs European Workplace Drug TestingDRUIDEWDTS screenEWDTS confirmationRIE Morphine2040 20 Codeine2040 20 6MAM20444 DHC2040 20 AMP504030 Met AMP504030 MDMA504030 Cocaine103088 BEC103088 Methadone205020 EDDP 5020NA Diazepam510 1 Nordiazepam110 1 Temazepam110 5 Oxazepam110 5 Nitrazepam110 5 Clonazepam110 NA Gabapentin 40 Tramadol 40 Buprenorphine 5510 Norbuprenorphine 55NA

17. What is in oral fluid? SMD clients 116 samples Morphine 47% Codeine 36% 6MAM 48% DHC 7% Methadone 62% Cocaine 18% Diazepam 59% Nordiazepam 55% Buprenorphine 17% Gabapentin 10% Amphetamine 3% MDMA 1% Tramadol 3% Metamphetamine 0%

18. Reporting Oral Fluid drugs Report currently has same 5 core tests as urine Opiate group negative – no specific drugs reported Opiate group positive – Morphine, codeine, 6MAM and dihydrocodeine reported as positive/negative Amphetamine; Cocaine; Methadone always reported Benzodiazepine group reported as neg or pos Other drugs only reported when present: MDMA, metamphetamine, gabapentin, tramadol, buprenorphine Appear on TRAK, SCIStore, Clinical Portal and EDT reports. Printed reports have mainly been switched off May drop amphetamine and replace with buprenorphine

19. What next? Pregabalin? Ethylphenidate? Oxycodone? THC?