Felgate P.P.. Sims D.N., Kirkbride K.P., Felgate H.E., James R.A., Vozzo P.C., Kostakis C.
Forensic Science SA, 21 Divett Place, Adelaide, South Australia 5000, Australia
Paramethoxyamphetamine (PMA) is a ring substituted phenethylamine derivative which has been used illi-citly in Australia since late 1994. Initially PMA had been sold under the «ecstasy» name normally asso-ciated with methylenedioxy- methylamphetamine (MDMA) but is now knowingly sought out as a party drug; colloquially known as «death». Our studies have indicated that PMA has been synthesized using the Leuckardt reaction and the manufacture of PMA is by design rather than accident. It would appear that South Australia is the source of PMA in Australia. The first Australian example of illicit preparations containing PMA was found in South Australia, and throughout the period 1995-2001 this state has recor-ded many more seizures of PMA than the rest of Australia. Although the appearance of tablets and cap-sules has varied over the years since 1995, the level of drug present has generally remained in the range between 50 and 70mg.
Routine analysis of illicit seizures since 1995 has never revealed the presence of other amphetamine-type stimulants such as MDMA or paramethoxy methylamphetamine (PMMA) in PMA preparations, unlike North America and Europe where mixtures with PMMA have been reported.
During the period September 1995 to October 2001 eleven PMA related deaths have occurred in South Australia. In these cases femoral blood PMA levels ranged from 0.24 to 23 mg/L, mean 3.9, median 1.7.
Significantly all the PMA deaths were thought to involve oral administration. Other members of the amphetamine drug type were found in nine of the eleven cases. Other States of Australia have recorded five PMA related deaths. Blood MA levels in three non-fatal cases and three cases where death was due to other causes have also been measured.
The number of PMA related deaths in South Australia are double those due to other amphetamines while at the same time seizures of PMA doses have remained at less than 5 % of the total number of ampheta-mine type drug seizures. This highlights the apparent greater toxicity of PMA.
PMA is now available in many parts of the world and would appear to be more toxic than MDMA. When used orally, hallucinogenic blood PMA levels range up to about 0.4 mg/l. Recent reports from North America and Europe have strengthened the view that levels above 0.5 mg/L appear likely to be associated with toxic effects and may be lethal especially in combination with other amphetamines.
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Identification of 11 opiates in urine with high performance liquid chromatography
Havard L„ Dupeyron J.R, Vautier S., Sandouk P., Chast F.Laboratoire de Toxicologie and Urgences Médico-Judiciaires, Hôtel-Dieu, 1 place du Parvis Notre-Dame, Paris, France
In forensic médecine, presence of opiates in urine has to be established with a reference method.
Furthermore, opiate compounds are often very close and difficult to differentiate though immunoassays (as morphine, codeine and monoacetylmorphine). From a toxicokinetic point of view, some substances with short elimination half life, cannot be found more than 24 h after absorption (morphine). Screening and confirmation have to be performed in less than 96 h, which represents the maximal duration of police cus-tody.
We use high performance liquid chromatography (HPLC) coupled to diode array detection drived by Millenium software (Waters®) for identification of illicit opiates in individual urine. Urine samples (30 mL) came from "Forensic Emergency Department". They are screened with EMIT® d.a.u.® reagents with a Cobas® Mira + autoanalyser. Urines positive for "opiates" are studied with HPLC: hydrolysis with P-glucuronidase at 40° C during 12 hours at pH=5.0. Extraction on Isolute HCX® column with fixation step at pH=4.0 and therefore elution at pH=8.0, with ammonium acetate buffer. Evaporation to dryness and dis-solution in 0,1 mL of mobile phase and injection of 50 uL Chromatographic device (Waters®) include a 4 lines HPLC pump, an automatic sampler, a Symmetry Cs column and detection monitoring at 220 nm.
Elution is performed by gradient during 20 min. Taking into account retention time and absorption, all the products are separated and identified as shown in the next table. The detection limit is estimated to 100 ng/mL. Time of analysis in our conditions is 48 h.
RT (min) A max
Pholcodine 4,9 210
Normorphine 5,2 210
Morphine 6,2 210
Norcodeine 10,7 212
Codeine 11,0 212
6-MAM 11,4 205
Codethyline 11,9 212
Hydrocodone 12,8 210
Norbuprenorphine 13,9 212
Buprenorphine 16,2 212
Methadone 17,0 195
This method allows separation with reasonable resolution of 11 opiates in a 20 minutes runtime; applied to 750 urine samples we confirm about 90% of them for opiates compounds.
Annales de Toxicologie Analytique, vol. XIV, n° 3, 2002
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Toxicoepidemiology among opiates users during police detention
Havard L.<'>. Dupeyron J.P.(I), Fleury F.t !\ Batista R.(1), Gamier M.<2), Chast F.(1>
(1) Laboratoire de Toxicologie,
(2) Urgences Médico-Judiciaires, Hôtel-Dieu, 1 place du Parvis Notre-Dame, Paris, France
The aim of this study was to establish the prevalence of isolate or associate opiate use in individuals admit-ted in the clinical forensic department (Urgences Médico-Judiciaires).
In order to check illicit opiates use, urinary samples are screened using immunochemical method (EMIT ® d.a.u.®). In case of positive immunochemical assay for opiates, a second analytical step includes identification with high performance liquid chromatography (HPLC) and diode array detection (DAD).
Morphine is the main substance identified (64.4 % of urine samples), alone (26 % of morphine positive samples) or associated with codeine and norcodeine (67 %), with normorphine (25.4 %), and with bupre-norphine and norbuprebupre-norphine (9.4 %),
Codeine was present in 432/770 samples (56 %). Codeine is the main substance in 72/432 positive samples (16.6 %); it is associated mainly to morphine (23.3 %), to morphine and norcodeine (16.4 %), to morphi-ne and normorphimorphi-ne (11.1 %), to norcodeimorphi-ne, morphimorphi-ne, normorphimorphi-ne (10 %) and to 6 monoacetylmor-phine (6-MAM) (5.5 %).
6-MAM was present in 3.5 % of the samples (never alone), associated to morphine (96 %), codeine (92 %), normorphine (65 %), norcodeine (15 %), norbuprenorphine, buprenorphine, pholcodine (4 %), and to hydrocodone (8 %). The presence of 6-MAM in urine is related to heroin abuse. Morphine may be a metabolite of 6-MAM or of heroin.
Combining HPLC with diode array detection is proved to be useful for identification of opiates in urine.
The complete analytical procedure is compatible with confirmation results within the duration of police custody.
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