The effects of synthetic cannabinoid UR-144 on the human body-A review of 39 cases.

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many 'legal highs', seized from the global drug market since the beginning of 2012. It has gained popularity as a 'legal' alternative to classic cannabis in countries where it was not controlled. Despite the widespread distribution of this substance, the data on its effects on the human body are scarce. Therefore, this paper describes the results of analysis and observed effects in 39 cases in which UR-144 was determined in blood. Symptoms were noted from the blood sampling forms filled out by the representative doctor. The determined concentrations of UR-144 were in the range of trace amounts (LOD-0.15ng/mL; LOQ-0.5ng/mL) up to 17ng/mL. The most common observed effects included slurred speech, dilated pupils, sluggish and abnormal pupillary reaction, cheerful behaviour, poor coordination, and staggering. Less frequently observed were: verbosity, narrow pupils, loss of consciousness, pale or reddened facial skin, blackout, euphoria, agitation, hallucinations, hindered communication, shaking hands, seizures, convulsions, somnolence, delayed movements, redness of the conjunctiva, and tachycardia. The discussed cases show the effects observed after UR-144 use. This study can assist in the recognition of possible effects caused by this substance.

3-Methylmethcathinone--Interpretation of Blood Concentrations Based on Analysis of 95 Cases.

3-Methylmethcathinone (3-MMC) has been one of the most popular new psychoactive substances (NPS) in Poland in recent years. 3-MMC was found in blood in 95 cases sent to the Institute of Forensic Research (IFR) during the two and a half year period, from 2013 to half of 2015. 3-MMC was determined in 13 and 48 cases in 2013 and 2014 year-round casework, respectively, while only in the first half of 2015 year it was present in 34 cases. In most cases, 3-MMC was detected together with other novel psychoactive substances and conventional drugs. Blood analyses for 3-MMC were carried out using liquid chromatography-tandem mass spectrometry (LC-MS-MS). The concentrations of 3-MMC in all 95 cases were in the range from traces (<1 ng/mL) up to 1.6 µg/mL (mean concentration 51.3 ng/mL, median 18.5 ng/mL). Concentration ranges in particular types of cases were respectively: DUID cases: 1-171 ng/mL; traffic accidents: <1-29 ng/mL; drug possession: 2-408 ng/mL; intoxication: <1-1600 ng/mL and other: <1-61 ng/mL. The parameters of the developed method such as the LOD (0.02 ng/mL) and LOQ (1 ng/mL) demonstrate that the method is well suited for the analysis of blood samples for 3-MMC and covers the range of typical blood concentrations.

The prevalence of new psychoactive substances in biological material - a three-year review of casework in Poland.

New psychoactive substances (NPS) pose a challenge for forensic and clinical toxicologists, as well as for legislators. We present our findings from cases where NPS have been detected in biological material. During the three-year period 2012-2014 we found NPS in 112 cases (out of 1058 analyzed), with 75 cases in 2014 alone. The prevalence of all NPS (15.1-17.6%) was similar to amphetamine alone that was detected in 15.1-16.5% of cases. The new drugs found belonged to the following classes: cathinones (88%), synthetic cannabinoids (5%), phenethylamines (3%), piperazines and piperidines (3%), arylalkylamines (1%) and other (1%). The drugs detected were (in the order of decreased frequency): 3-MMC (50), α-pyrrolidinopentiophenone (α-PVP) (23), pentedrone (16), 3',4'-methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP) (12), synthetic cannabinoid UR-144 (7), ethcathinone (5), mephedrone (5), methylenedioxypyrovalerone (MDPV) (4), 4-methylethcathinone (4-MEC) (3), buphedrone (3), desoxypipradrol (2-DPMP) (3), methylone (2) and 2C-B (2). In single cases, 2-methylmethcathinone (2-MMC), 2C-P, eutylone, 25I-NBOMe, meta-chlorophenylpiperazine (mCPP), ephedrone, methiopropamine (MPA), and 5-(2-aminopropyl)benzofuran (5-APB) were found. One NPS was the sole agent in 35% of all cases, and two or more NPS were present in 19% of cases. NPS (one or more) with other conventional drugs (like amphetamines, cannabinoids, cocaine, and benzodiazepines) were detected in most (65%) of the cases. NPS were very often detected in the blood of drivers which was a challenge for toxicologists due to a lack of data on their influence on psychomotor performance. A review of concentrations showed a wide range of values in different types of cases, especially driving under the influence of drugs (DUID) and intoxication.

Analysis of 4-MEC in biological and non-biological material--three case reports.

4-Methylethcathinone (4-MEC) is a designer drug that is structurally similar to mephedrone. This substance was identified in many drug seizures analyzed in the Institute of Forensic Research (IFR). This paper describes three of the first cases in which both powders and biological material were secured at the same time and delivered to the IFR for toxicological analysis. The first case concerned a man who died in a car crash. The second case describes a death associated with multiple-drug intake, including 4-MEC. In this case, however, the death was the result of an overdose of para-methoxyamphetamine (PMA). In the third case, the man was arrested for possession of illicit drugs. Analysis of powders was carried out using gas chromatography-mass spectrometry (GC-MS) and high pressure liquid chromatography with diode array detection (HPLC-DAD). The purity of 4-MEC found in powder samples was 51% and 78%. Analyses of biological material were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 4-MEC was found in blood samples at concentrations of 46, 56 and 152 ng/mL.

Analysis of MDPV in blood--determination and interpretation.

3,4-Methylenedioxypyrovalerone (MDPV) is a cathinone derivative. It has recently been classified as a controlled substance in many countries. This substance is a stimulant that can be snorted, smoked or taken orally. MDPV has been determined in biological material from four cases sent to the Institute of Forensic Research in 2011. In the first case, a passenger car crashed into a truck; the driver of the vehicle suffered severe injuries, resulting in his death. In the second case, biological material was obtained from the decedent male individual, who did not wake up after a party. In the two cases, the material was secured on suspicion of the possession of narcotic drugs or psychotropic substances, in which the suspects admitted to using "legal highs." The MDPV blood concentrations of the deceased driver and deceased man were 38 and 17 ng/mL, respectively. In the two other cases, the determined concentrations were 306 and 124 ng/mL. However, MDPV was not the sole substance detected in these cases: in each, other drugs were also determined. Analyses of blood were conducted using liquid chromatography-tandem mass spectrometry.

[Resurgence in paramethoxamphetamine use. Review of poisonings and two recent cases study]. / Powrót do uzywania parametoksyamfetaminy. Przeglad zatruc i studium dwóch nowych przypadków.

Two recent cases of death due to p-methoxyamphetamine (PAM) intake, a methoxylated phenethylamine derivative, were described and compared with previous PMA related deaths that occurred in many countries. Following a review of the available literature from 1974 to 2011 three periods of resurgence of an unsuspected increase of lethal PMA causation were considered. Signs of intoxications, concentrations of PMA found in biological materials were discussed. Based on the case reports can be concluded the great number of victims were unconscious of taking PMA as substitute of MDMA. Two new methods for screening, identification and quantification of amphetamine derivatives in biosamples (blood and urine) using LC-MS/MS techniques were developed. The methods have proven to be appropriate for clinical and forensic toxicology purposes.

[Determination of fentanyl, atropine and scopolamine in biological material using LC-MS/APCI methods]. / Oznaczanie fentanylu, atropiny i skopolaminy w materiale biologicznym metodami LC-MS/APCI.

In this paper methods for determination of fentanyl (FL) and its three analogues: alfentanyl (AL), sufentanyl (SL) and remifentanyl (RL), atropine (AT) and scopolamine (SK) in biological material (whole blood and urine) using liquid chromatography atmospheric pressure chemical ionisation mass spectrometry technique (LC-MS/ APCI) are presented. Separation of analytes was performed in gradient conditions, using a LiChroCART LiChrospher 60 RP-select B column. The mobile phase consisted of 0.1% (v/v) formic acid in water and in acetonitrile. Target analytes were isolated from biological matrices using liquid-liquid extraction technique with n-butyl chloride or diethyl ether as extraction solvents. The validation data of the methods were: limit of detection (LOD, S/N = 3) and limit of quantification (LOQ, S/N = 10) - 0.05 and 0.25 ng/ml for FL, and 0.7 and 0.9 ng/ml for AT, both in blood, whereas 1.9 and 2.1 ng/ ml for FL, and 0.6 and 0.9 ng/ml for AT in urine. Calibration curves showed linearity in concentration ranges from LOQ to 25 ng/ml in blood and from LOQ to 50 ng/ml in urine. Determination coefficients (R2) of linear regression equation were higher then 0.98. Extraction recovery, intra-day precision (CV(w.g.)) and inter-day precision (CV(m.g.)) were determined at analytes and internal standard (I.S.) concentration of 5 ng/ml for blood, and at analytes and I.S. concentrations of 20 and 5 ng/ml, respectively for urine. Extraction recovery ranged from 76 to 100% for blood and 53--72% for urine. CV (n=5) and CV(m.g.) (n=15) equal from 4.8 to 7.5% and from 6.8 to 16.2% respectively for blood, and from 4.3 to 5.4% and from 5.8 to 9.5% for urine. The application of elaborated methods of the determination of FL, AT and SK in blood and urine for 8 expert opinions elaborated at the Institute of Forensic Research in Krakow is described. FL was detected and quantified in 3 cases, whereas AT and SK in 7.

Fentanyl and its analogues in clinical and forensic toxicology.

Fentanyl and its analogues are commonly named synthetic opiates. Some compounds from fentanyl group (e.g. fentanyl, alfentanil, sufentanil, remifentanil) are used as anaesthetic and analgesic of high potency and short duration of action. Effects of acting fentanyls are indistinguishable from those produced by nasal inhalation of street heroin. In view of this, fentanyls are very "attractive" for the narcotic market. In least years an increase in number of reports about illegal production and non-medical use of fentanyl and its analogues have appeared. Numerous fentanyl analogues are sold under one name synthetic heroine or China white. Fentanyl and its analogues also can be used as gas warfare agents. One of fentanyl-related compound was used during action of easing hostages from Dubrovka theatre. Because of respiratory depression, which was caused by used compound, died over 100 hostages. Because of high potency fentanyl-related compounds are used in very low doses. So fentanyls appear in biological material in very low concentrations, not higher than several nanograms per millilitre or per gram. The drugs in these concentrations cannot be detected by means of routinely used screening procedures. Therefore direct methods for determination of this group of compounds are needed. Screening method for determination of fentanyl and its analogues was elaborated and validated. Liquid chromatography-mass spectrometry (LC/MS) technique was applied. The method is characterised by the limit of quantification (LOQ) and the limit of detection (LOD) ranged from 0.6 to 2 ng/ml and from 0.2 to 0.6 ng/ml, respectively for four above-mentioned compounds. The method was used for determination of fentanyl in three forensic cases. The blood, bile and blood from lung samples were taken during autopsy of persons who died shortly after surgical procedure in which fentanyl was used as an adjunct to general anaesthesia.