HELD ON 12 FEBRUARY 1999 AT THE LINNAEAN SOCIETY, PICCADILLY,LONDON
Original Document
Phenethylamines and the Misuse of Drugs Act. By Dr Les King, Forensic Science Service, London.
Dr Les King outlined the Misuse of Drugs Act and its application primarily to the phenethylamine group of compounds.
All Class A phenethylamines are ring substituted and are hallucinogenic. These are listed both specifically and generally under the Act. Other phenethylamines are found in Class B (amphetamine and methylamphetamine) and Class C (benzphetamine).
The book by Alex Shulgin PIHKAL (Phenethylamines I Have Known And Loved) contains 170 ring substituted compounds and these are covered under the Act as Class A drugs. Around 34 compounds listed in the book together with 4-methylthio-amphetamine (4MTA) were found to have escaped the general classification, but these are now to be covered by legislation under Statutory Instrument 1999.
A series of other drugs were described including the Class B N-hydroxy-amphetamine which when swallowed is converted into amphetamine – a form of covert production.
Other drugs that may soon appear are FLEA, BOB, and MDMP. It is thought that ‘ecstasy’ is currently MDMA, with MDEA and MDBD virtually having disappeared from the drugs of abuse scene.
PRESENT
K Clarke (Chairman)
P Minty (Vice Chairman)
J Seviour (Treasurer)
S George (Secretary)
B Smith
A Pierce
J Wicking
D Whittle
APOLOGIES
None
PREVIOUS MINUTES
Previous minutes were accepted.
TREASURER’S REPORT
The current balance of the Group £4,559.77, of which £3,894.52 is held in the current account and £575.25 is held in the deposit account. Corporate membership is still being reviewed. Currently there are 10 paid-up corporate members.
The balance sheet still needs to be audited and non-committee members are still being sought to perform this task.
The cost of the meetings is still increasing due to the growing number of members attending needing to be catered for. The average attendance of the meetings is 48 delegates. Owing to the current balance of the Group, it will be unnecessary to increase the membership subscriptions this year.
SECRETARY’S REPORT
The new Executive Committee and the membership list as of December 1998 was circulated with the last minutes. It should be remembered that the subscription for ordinary members runs from January to December, and so this will be the last minutes circulated to those who se subscriptions have lapsed – be warned.
The current membership lists 2 Honorary life members, 89 ordinary members and 10 corporate members. Applications for membership have been received from Stephanie Braines (MTU), Tony Dedman (Ealing Hospital NHS Trust), Prof. Bob Forrest (Forensic Pathology, Sheffield), Howard Mason (HSL), Hannah Morgan (SIMBEC Ltd), David Mortimer and Paul Whitaker (Leicester Royal Infirmary). These will be put to the Group this afternoon.
Today’s meeting has been sponsored by Cozart Bioscience Ltd. The meeting has again been granted 3 CME points and 0.5 CPD points. As stated previously, from April both the IBMS and the Royal College will be using CPD as the unit of continuing professional development for logbooks, but the requirements and allocation of units from the two sources will be at the current rate.
CHANGE OF ADDRESS
Kathy Clarke Forensic Coordinator,
Forensic Alliance Ltd.
F5 Culham Science Centre
Abingdon, Oxfordshire. OX14 3ED
Tel 01235 551804
Fax 01865 407431.
FUTURE MEETINGS
The next meeting is to take place on Friday 16th April. The October meeting is to be a full day joint meeting with the Belgian and Luxembourg Toxicologists held on the 15th of October at the Royal Entomological Society. Further details to follow. The Linnaean Society has confirmed the bookings for the rest of 1999 as follows: -
June 11th
December 10th
CHAIRMAN’s REPORT
There will be a summary of the meeting held by the advisory group for the Register of Forensic Scientists written and posted on the website – but not for open display. Both the Chairman and Brian Smith attended the meeting on behalf of the Group
The Group has been asked by Cozart to set up a user group for their kits. It was thought that a third party should be used to prevent the Group being seen as endorsing the products. One option would be to ask John Wilson to contact UKNEQAS members who use Cozart reagents to see if they require a subset for QC returns.
Workplace guidelines are to be discussed using the website due to the working party meeting schedule. The group has a recognised input with each member of the working party hosting a meeting and arranging an independent chair.
Due to the problems of getting speakers for the meetings, it was suggested that a questionnaire should be sent out to canvass members for their suggestions of topics to be covered and potential speakers.
The April meeting is likely to be based around controlled drugs and extraction techniques. A potential sponsor is High Standard Products who will be in attendance today as a guest to review the format of the meetings prior to applying to become a corporate member.
AOB
The post office regulations concerning transport of specimens are still under review. These issues need to be put to the Group to ensure appropriate distribution of the information.
Andy Marsh wishes to know what people consider to be a fatal methadone concentration – this will be put to the Group today for a consensus view.
The Group will be asked if anyone is able to analyse low level THC in plasma. Further information will be available from Brian Smith this afternoon.
THE NEXT MEETING OF THE EXECUTIVE COMMITTEE WILL BE HELD ON
FRIDAY 16 APRIL 1999, 10:30 AM AT THE LINNAEAN SOCIETY.
SUMMARIES OF TALKS PRESENTED: -
Salivary drug testing. By Dr Chris Hand, Cozart Bioscience Ltd, Abingdon.
Cozart considered different matrices for near patient and roadside testing. Each matrix was reviewed in terms of ease of specimen collection, non-invasive techniques of collection, privacy protection, and ease of adulteration. These criteria ruled out urine, blood, hair, and sweat, leaving saliva as the preferred matrix. With saliva there is no lag time, and so concentrations relate to actual impairment rather than past abuse. The window of detection depends largely on the dose of the drug taken, and the elimination profile of the drug.
Initial studies comparing saliva to urine analysis using the microplate method (ELISA) found good agreement for 124 specimens screened for opiates. Some differences were observed due to different cut-off limits. In addition, there were 12 refusals for urine specimens but no refusals for saliva specimen collection. Pilot studies were performed by the Strathclyde, Lancashire, Cleveland and Sussex police using 550 samples taken at the roadside. The feedback was positive from both the police and public.
The saliva is collected using a RapidScan collection device with an indicator window that turns blue when 1 mL of saliva is collected. This is then transferred to an immunoassay cartridge to mix with buffer (1:1 dilution). The cartridge is placed into an analytical device and after 5 minutes a result for amphetamines, benzodiazepines, cannabinoids, cocaine and opiates is given. The assay for methadone is under development. Some of the assay specifications are: -
| Target Group | Calibrator | Cutoff (ng/mL) | Cross-reactivity |
| Benzodiazepines | Temazepam | 1.0 | Benzodiazepine group |
| Cannabinoids | THC | 50.0 | THC (stays in the mouth after smoking) |
| Amphetamines | MDMA | 20.0 | MDEA, MDBD, methylamphetamine |
| Opiates | Morphine | 20.0 | Heroin, codeine, DHC, 6-MAM |
The cutoff concentration is that in saliva prior to the 1:1 dilution with buffer, indicating the sensitivity of the technique.
The device has the ability to test for multiple drugs, it is easy to use and gives rapid results, which are compiled electronically removing the subjectivity of the screening technique. The accuracy of the technique has been established against ELISA for opiates and HPLC for benzodiazepines.
The identification of 4-MTA by GC-MS and NMR, and seizure data. By Dr Chris Groombridge, Forensic Science Service, London.
18 months ago Thames Valley police found 4 packets of tablets labelled "S5 the one and only dominator". They were 14 x 4.7 mm in size, gave a negative result with the marquis (not ecstasy) and cobalt thiocyanate (not cocaine). Proton NMR with deuterium oxide extraction of the salt form gave a peak at 4.35 min (caffeine at 5.25 min and bupivicaine internal standard art 6.75 min.). GC-MS produced ions at 44,138,137,122,91,78,139 in order of decreasing abundance. The compound was not in the library and so was not controlled, but the NMR gave an amphetamine like result.
A base extraction into chloroform prior to NMR analysis gave a pattern that was similar to amphetamine, but with a substitution in the 1 or 4 positions, and a methyl group not attached to the N, O or ring. Therefore a methylthio group was probably involved. HFB derivatisation with GC-MS was used to determine the molecular ion. A 377 ion was found (less HFB gives 181), combined with the NMR results suggested a sulphur group. From the combined studies 4-methylthio-amphetamine was characterised.
The work described above was published in Microgram (Groombridge, 1998, 31, 150-158). Nichols (Eur. J. Pharmacol. 1992, 229, 31-38) described 4-MTA as a potent non-neurotoxic serotonin releasing agent. In 1998 a seizure of 25,000 tablets ecstasy style tablets 9.2 mm in diameter were all found to contain 100 mg of 4-MTA per tablet.
Measurement of 4-MTA in clinical and post-mortem specimens. By Simon Elliott, City Hospital NHS Trust, Birmingham.
The first reported case of 4-MTA in the UK was admitted to the Hospital 4/7/98 and was thought to have taken an ecstasy overdose. Kept under observation and seemed to be recovering but then collapsed and required intubation and ventilation, and survived. MDA and MDMA were found along with an unidentified compound.
The first reported death in the UK was from a subject at the Shepton Mallet rave. Specimens were received 26/7/98 again from a suspected ecstasy overdose victim. The mass spectral data was sent to Dr Les King, who confirmed the presence of 4-MTA. A tablet was then analysed in-house by GC, GC-MS and HPLC diode array and confirmed the findings of the first case admitted to the hospital in July.
The third case studied was from an 18-year-old subject thought to have taken an amphetamine or ecstasy overdose. The patient was admitted on 16/8/98 with convulsions and respiratory depression requiring intubation and ventilation. Amphetamine, pseudoephedrine and 4-MTA were detected.
The last case involved a patient admitted to the ITU on 28/9/98 convulsing and requiring ventilation. MDMA, MDA, amphetamine and 4-MTA were all detected in this patient.
The results of the HPLC diode array analyses are collated as follows: -
| Case | 4-MTA (mg/L) | Other drugs detected |
| 1 | 0.19 | MDMA, MDA |
| 2 | 4.20 peri-mortem 4.60 post mortem |
None |
| 3 | 0.13 | Amphetamine, pseudoephedrine |
| 4 | 0.76 | Amphetamine, MDMA, MDA |
From this data a proposed toxicity range has been suggested for 4-MTA in the absence of other drugs: -
| Moderate toxicity | 200 – 600 µg/L |
| Severe toxicity | above 600 µg/L |
| Fatality | above 1,500 µg/L |
Police investigations of the Shepton Mallet Rave. By DC Paul Thomas, National Crime Squad, Bristol.
Rene Saunders aged 22 from Shrewsbury died 26th July 1998. He had attended a rave organised by ESP Promotions held and the Bath and West Show site. There were 9,250 people who attended the rave, all were searched, amnesty bins were provided for the disposal of drugs, there was a security firm on site and police on the roadways outside the site.
He was found at the side of the road and sent to hospital but believed to be dead at the scene. Those with him had left the scene, and it was thought to be a drug-related death. It was discovered that he had taken "flatliners" (4-MTA) at the rave, and that he enjoyed taking them. SOCO were called and all at the scene (20-30 people) were arrested for drug searching.
Yeovil police found no drugs on the people searched, and amnesty was offered provided that full information was disclosed about the incident.
Some subjects related their experiences with flatliners; some had no pleasurable effects, some were sick instantly, some had stomach cramps and chronic headaches especially around the eye sockets. One subject claimed to have taken 1g of base amphetamine (uncut and relatively pure) at 7:00 p.m., 1 ecstasy tablet at 11:00 p.m., 1 flatliner at 12:30 p.m. and 1 flatliner at 01:30 a.m. He was incoherent and tried to break into a police car in the police station whilst under observation. He was shaking with his eyes rolled back so that only the whites of his eyes could be seen. He was still "bad" until 11:00 p.m. that night, but he stated that they had "all been like it before and that the police shouldn’t worry about it".
There were 31 witnesses but no one had seen Rene Saunders take anything, but no one said he would have taken them against his will.
The progression of the toxicity of the case was as follows (witness accounts): -
| 22:00 | OK |
| 22:30 | ?OK, stomach cramps, fairly sick |
| 01:00 | Cold, stomach cramps, fairly sick, shaking |
| 01:30 | Normal self |
| 02:00 | Legs shaking, seemed OK |
| 02:30 | Slumped on the ground, out of it, shaking |
| 03:00 | Flat out looking tired |
| 05:00 | Lying on the ground, off his face, heavily drugged |
| 06:15 | Shaking, sweating, not able to speak properly |
| 06:45 | On his back |
| 07:00 | Unable to stand, in a trance |
| One witness stated Going blue in the lips, very hot, shaking, moaning, eyes rolling back | |
| 10:00 | Trouble breathing, lips and face blue, sweating, foaming at the mouth, lost consciousness |
| 13:00 | Time of death |
Accidental death due to 4-MTA ingestion as verdict
At the rave all drugs including ecstasy and flatliners were £10 per tablet/dose
Typical rave costs are £150 to £200 per head to include ticket, travel, bottled water and drugs.
MINUTES OF THE LTG BUSINESS MEETING HELD ON
12 FEBRUARY 1999 AT THE LINNAEAN SOCIETY, PICCADILLY, LONDON
| PRESENT | APOLOGIES | |
| B Smith | D Whittle | L Gibbs |
| R Mayes | S Athwal | B Spragg |
| S George | J Wicking | M Ruprah |
| C Meadway | D Berry | T Simons |
| K Clarke | R Braithwaite | J Eastwood |
| T Richardson | D Robertshaw | D Martinez |
| P Astley | J Rees | M Butcher |
| A Pierce | D Wood | P Mace |
| J Seviour | A Markham | J Fry |
| J Fry | P Minty | I Watson |
| S Elliott | P Kindred | A Johnston |
| A Hiscutt | B Widdop | A Marsh |
| G Turner | R Flanagan | M Coakley |
| J Christofides | J Ramsey | J Morton |
| C Dawson | T Crane | |
| I Marsh | S Biddle | |
| S Lucas | A Clatworthy | |
| D Pearse | C Haycock | |
| C Hand | E Harvey | |
| F Quinlivan | A Newsam | |
| C Wilkinson |
| GUESTS | |
| F Burton | S Ciniawskyj |
| H Rea | S Braines |
| R Quaicoe | P Emcoda |
| D Gibson | L King |
| C Groombridge | P Thomas |
| H Morgan |
APPLICATIONS FOR MEMBERSHIP
Applications for membership were received from Stephanie Braines (MTU), Tony Dedman (Ealing Hospital NHS Trust), Prof. Bob Forrest (Forensic Pathology, Sheffield), Howard Mason (HSL), Hannah Morgan (SIMBEC Ltd), David Mortimer and Paul Whitaker (Leicester Royal Infirmary) were put to the Group and all were accepted.
FUTURE MEETINGS
The future meeting dates are confirmed as follows: -
| June 11th | Title and speaker to be arranged |
| October 15th | Full day meeting with the BLT - Title and speakers to be arranged |
| December 10th | AGM and members papers |
Business Meeting
The new post office regulations appear to be in disarray, with no one knowing whether or how they will apply to the transport of clinical material to laboratories for analysis. The current maximum transportable volume is only 50 mL. The application of this limit to 24 hour urine collections, and other large volume specimens would increase the profit margins of the Post Office at our expense – although discounts are available following the purchase of a Post Office License which promises the return of the postage if the specimens do not arrive!!! The DTI and working group on Pathology are against the new guidelines – discussions are ongoing.
Andy Marsh wishes to know what people consider to be a fatal methadone concentration following from the presentation given by Manjit in December where "an independent pathologist stated that concentrations greater than 5 mg/L are considered to be toxic". There will be therapeutic and toxic drug ranges given in the next edition of the TIAFT Bulletin.
There is an ongoing study into the therapeutic use of cannabis under the control of Tony Moffat from the Royal Pharmaceutical Society. This is a bioequivalence study for the treatment of multiple sclerosis and pain relief. The analytical phase requires THC and CBD and their metabolites to be determined down to 1 ng/mL in plasma. Anyone interested should contact Tony Moffat or Brian Smith for further information.
Dave Robertshaw requested any information regarding any published articles stating why drugs of abuse screening should be performed and clinical support for drug monitoring.
Following from a GHB (gamma-hydroxy butyrate) and amphetamine death there is a move to ban GHB. GBL (gamma-butyrolactone) sold as "Blue Nitro", is a precursor of GHB and converts to GHB when swallowed. GBL in basic conditions gives GHB which in acidic conditions is converted back to GBL. GBL is available from Sigma.
The UK Workplace Drug Testing Group had its first meeting to discuss specimen collection, the website will chart the progress of this group. The European Society for Workplace Drug Testing will publish its findings in the TIAFT Bulletin
The London Toxicology Group is a recognised member of the steering group of the Forensic Sciences Advisory Group overseeing the construction of the Register for forensic practitioners. The summaries of the meetings will be placed on the website, and the current plan is to finish the establishment of the register by June 1999.
DATE OF NEXT MEETING
16 APRIL 1999, MEETING ROOM, LINNAEAN SOCIETY,
BURLINGTON HOUSE, PICCADILLY, LONDON