Determination of Δ9-tetrahydrocannabinol, 11-nor-carboxy-Δ9-tetrahydrocannabinol and cannabidiol in human plasma and urine after a commercial cannabidiol oil product intake.

PURPOSE: Cannabidiol (CBD) products are widely used for pain relief, sleep improvement, management of seizures etc. Although the concentrations of Δ9-tetrahydrocannabinol (Δ9-THC) in these products are low (≤0.3% w/w), it is important to investigate if its presence and/or that of its metabolite 11-nor-carboxy-Δ9-THC, is traceable in plasma and urine samples of individuals who take CBD oil products. METHODS: A sensitive GC/MS method for the determination of Δ9-THC, 11-nor-carboxy-Δ9-THC and CBD in plasma and urine samples was developed and validated. The sample preparation procedure included protein precipitation for plasma samples and hydrolysis for urine samples, solid-phase extraction and finally derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide) with 1% trimethylchlorosilane. RESULTS: For all analytes, the LOD and LOQ were 0.06 and 0.20 ng/mL, respectively. The calibration curves were linear (R2 ≥ 0.992), and absolute recoveries were ≥91.7%. Accuracy and precision were within the accepted range. From the analysis of biologic samples of 10 human participants who were taking CBD oil, it was realized that Δ9-THC was not detected in urine, while 11-nor-carboxy-Δ9-THC (0.69-23.06 ng/mL) and CBD (0.29-96.78 ng/mL) were found in all urine samples. Regarding plasma samples, Δ9-THC (0.21-0.62 ng/mL) was detected in 10, 11-nor-carboxy-Δ9-THC (0.20-2.44 ng/mL) in 35, while CBD (0.20-1.58 ng/mL) in 25 out of 38 samples, respectively. CONCLUSION: The results showed that Δ9-THC is likely to be found in plasma although at low concentrations. In addition, the detection of 11-nor-carboxy-Δ9-THC in both urine and plasma samples raises questions and concerns for the proper interpretation of toxicological results, especially considering Greece's zero tolerance law applied in DUID and workplace cases.

Vitreous humor in the forensic toxicology of quetiapine and its metabolites.

PURPOSE: Τhe aim of the present study was to investigate the use of vitreous humor as an alternative biological material in forensic toxicology for the determination of quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine. The distribution of these substances in vitreous humor was studied by determining and correlating their concentrations in vitreous humor with the respective concentrations in blood. METHODS: During this study, a method for the determination of these substances was developed, validated and applied to postmortem samples obtained from 16 relative forensic cases. The sample preparation procedure included the isolation of the analytes from vitreous humor and blood samples using solid-phase extraction, with Bond Elut LRC C18 columns followed by derivatization with BSTFA with 1% TMCS prior to GC/MS analysis. RESULTS: The developed method is characterized by a dynamic range of 10.0-1000.0 ng/mL (R2 ≥ 0.991) for the three substances, with a limit of detection and quantification of 3.0 and 10.0 ng/mL, respectively. Accuracy and precision were below 8.09% and 8.99%, respectively, for both biological materials, while absolute recovery for the three substances was greater than 81%. According to the results, quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine are easily distributed in vitreous humor. CONCLUSION: The results of the study indicate the usefulness of vitreous humor in toxicological analysis for the determination of these substances, especially when the traditional biological materials are not available. The levels of quetiapine and its metabolites in vitreous humor as well as the vitreous humor to blood concentration ratios can provide important information for a more thorough toxicological investigation of forensic cases.

Prenatal Exposure to Bisphenol A: Is There an Association between Bisphenol A in Second Trimester Amniotic Fluid and Fetal Growth?

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual's diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = -0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility.

PURPOSE: Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. METHODS: This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. RESULTS: The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. CONCLUSION: FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Monitoring of land surface subsidence using persistent scatterer interferometry techniques and ground truth data in arid and semi-arid regions, the case of Remah, UAE.

The United Arab Emirates (UAE) is located in an arid desert climate with very limited water resources and scarce rainfall. Along with the fast development of the country, the water demand for agriculture, industrial, and domestic purposes increased and led to diminishing groundwater resources. In this study, we explore the land surface deformations due to groundwater overexploitation in the agricultural area of Remah by analyzing Sentinel-1 data between 2015 and 2019 with the novel Parallelized-Persistent Scatterer Interferometry (P-PSI) technique. The detected land surface deformations have been correlated to the recorded groundwater levels at nearby water wells. This study detected land surface deformations in a form of an extensive subsidence bowl (with 28.5 km in diameter) with a maximum subsidence rate of 40 mm/year and a standard deviation within the bowl of less than 2 mm/year. The detected subsidence was associated with a 12 m drop in the water table level within the study area. The Persistent Scatterers with the highest deformations rate were spatially correlated with the depression cone of the groundwater level. These findings provide useful insights in understanding the groundwater regime of the area and have an important role in assessing regional hazards and driving mitigation measures towards managing uncontrolled groundwater overexploitation for sustainable management of groundwater resources.

Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method.

Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00-500.0ng/mL (R2≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04-7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.

Multi-Temporal InSAR Analysis for Monitoring Ground Deformation in Amorgos Island, Greece.

Radar Interferometry is a widely used method for estimating ground deformation, as it provides precision to a few millimeters to centimeters, and at the same time, a wide spatial coverage of the study area. On July 9, 1956, one of the strongest earthquakes of the 20th century in the area of the South Aegean, occurred in Amorgos, with a magnitude of Mw = 7.7. The objective of this research is to map ground deformation in Amorgos island, using InSAR techniques. We conducted a multi-temporal analysis of all available data from 2003 to 2019 by exploiting historical ENVISAT SAR imagery, as well as the dense archive of Sentinel-1 SLC imagery. Persistent Scatterer Interferometry (PS) and Small Baseline Subset (SBAS) methods were implemented. Results of both data-sets indicate a small-scale deformation on the island. A multi-track analysis was implemented on Sentinel-1 data to decompose the line of sight velocities to vertical and horizontal. The central south coast is experiencing horizontal movement, while uplift of a maximum value of 5 mm/y is observed in the southeastern coast. The combination of the good spatial coverage achievable via InSAR, with GPS measurements, is suggested an important tool for the seamless monitoring of Amorgos island towards tectonic hazard estimation.

Incidence of fatalities of road traffic accidents associated with alcohol consumption and the use of psychoactive drugs: A 7-year survey (2011-2017).

Driving under the influence of alcohol and/or psychoactive substances increases the risk of severe, even fatal motor vehicle accidents. The aim of this descriptive study was to present the impact of alcohol and/or psychoactive substances on fatal road traffic accidents (RTAs) during the period 2011-2017. For this purpose, the toxicological investigation reports from the Department of Forensic Medicine and Toxicology of the University of Athens were used. In total, 1,841 (32.2%) of the autopsies conducted by the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens over a 7-year period (2011-2017) were victims of fatal RTAs. Blood and urine samples were collected and analyzed for the presence of alcohol and psychoactive substances. The results were classified according to sex, age, victim (car driver, motorcyclist, pedestrian, or passenger) and the date the accident occurred (day, month and year). In total, 40.7% of the RTA-related fatalities were associated with alcohol consumption, among which 20.3% were car drivers. Of these, 87.3% were male victims. A higher frequency of RTA-related fatalities associated with a blood alcohol concentration (BAC) >110 mg/dl was encountered in younger compared with older age groups. Psychoactive substances were detected in 348 (18.9%) of the victims (cannabis in 46.6% of these, benzodiazepines in 25.9%, opiates in 16.4% and cocaine in 11.1% of these). The percentage of the RTA-related victims that had consumed alcohol in combination with other psychoactive substances was 4.5%. On the whole, the findings of this study suggest that alcohol and psychoactive substances are probably risk factors for RTA-related fatalities.

A GC-MS method for the determination of furanylfentanyl and ocfentanil in whole blood with full validation.

PURPOSE: Fentanyl analogues are popular in recent years among drug addicts and have been related to many overdoses and deaths worldwide. Furanylfentanyl, ocfentanil, acetylfentanyl and butyrfentanyl are among the most common of these drugs. Methods for the determination of furanylfentanyl and ocfentanil by gas chromatography-mass spectrometry (GC-MS) in biological samples do not exist, and therefore, their development would be extremely useful for routine toxicological analysis. METHODS: A GC-MS method was developed and fully validated for the determination of furanylfentanyl and ocfentanil in whole blood. This method was also suitable for the determination of acetylfentanyl and butyrfentanyl. The method included solid-phase extraction after protein precipitation using acetonitrile, and it was applied during the toxicological investigation of forensic cases. Methadone-d 3 was used as internal standard for the quantification of the analytes. RESULTS: The limit of detection and limit of quantification values were 0.30 and 1.0 ng/mL for furanylfentanyl and ocfentanil and 0.15 and 0.50 ng/mL for acetylfentanyl and butyrfentanyl, respectively. The calibration curves were linear (R 2 ≥ 0.993) from 1.00 to 100 ng/mL for furanylfentanyl and ocfentanil and from 0.50 to 50.0 ng/mL for acetylfentanyl and butyrfentanyl. The recoveries were not lower than 85%, while accuracies and precisions were not greater than 6.0% (% error) and 8.0% (% relative standard deviation), respectively, for all four fentanyl analogues. CONCLUSIONS: The developed method is the first one in the literature for the detection of furanylfentanyl and ocfentanil in biological fluids by GC-MS, and it provides very high sensitivity comparable to that by liquid chromatography-tandem mass spectrometry.

A fully validated method for the simultaneous determination of 11 antihistamines in breast milk by gas chromatography-mass spectrometry.

Antihistamines are excreted into breast milk in small amounts; however, there are no adequate published studies or data concerning their effects on newborns and safety during breastfeeding. Thus, the development of sensitive and specific methodologies for the determination of antihistamines in breast milk is critical. A simple and sensitive GC-MS method for the simultaneous determination of 11 antihistamines (diphenhydramine, orphenadrine, chlorpheniramine, dimethindene, meclozine, hydroxyzine, loratadine, desloratadine, cetirizine, rupatadine and ebastine) in breast milk was developed and validated. The antihistamines were solid-phase extracted and derivatized with acetic anhydride and n-propanol. Diazepam-d5 , hydroxyzine-d4 and cetirizine-d8 were used as internal standards. Absolute recovery values for all analytes ranged from 70.5 to 120.0%, while the limits of detection and quantification for all analytes were 1.50 and 5.00 ng/mL, respectively. All calibration curves were linear (R2 ≥ 0.990) within the range 5.00-1000.0 ng/mL. Accuracy (Er ) ranged between -7.6 and 7.0%, while precision (RSD) was <12% for all antihistamines. The developed method is suitable for the investigation of antihistamine-related clinical cases, as well as for pharmacokinetic and breastfeeding safety studies.

Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil.

PURPOSE: Ocfentanil and carfentanil are two potent synthetic opioids that are analogues of fentanyl and are actively involved in the recent fentanyl crisis. The aim of this review is to provide all the available information on these two fentanyl analogues. METHODS: All reviewed information was gathered through a detailed search of PubMed and the World Wide Web using relevant keywords. RESULTS: Like most of the members of the family of fentanyls, they are either sold as heroin to unsuspecting users or used extensively to lace heroin street samples. Despite the fact that ocfentanil was studied clinically in the early 1990s, it did not manage to find its place in clinical practice. On the other hand, carfentanil is mainly used today as an anesthetic agent in large animals. Ocfentanil and carfentanil are used and abused extensively, mainly in Europe and in the United States. As a result, they are the cause of some verified intoxication cases and deaths worldwide. This review provides information concerning chemistry, synthesis, prevalence, pharmacology, and toxicology, as well as the current legal status of these two fentanyl analogues. Analytical methods developed for the determination of ocfentanil and carfentanil in biological specimens and seized materials, as well as related intoxication and lethal cases are also presented. CONCLUSIONS: Ocfentanil and carfentanil are undeniably very dangerous opioid drugs and a very serious matter of concern for public safety. The authorities should take the appropriate actions to avoid the expansion of this threat by taking proper and prompt measures.

Development and validation of a GC-MS method for the determination of hydroxyzine and its active metabolite, cetirizine, in whole blood.

A simple, rapid, sensitive and accurate gas chromatography-mass spectrometric method was developed and validated for the simultaneous determination of hydroxyzine and cetirizine in whole blood. Solid-phase extraction procedure using Bond Elut LRC Certify II columns was used for the isolation of hydroxyzine and cetirizine from 1mL whole blood followed by derivatization with a mixture of acetic anhydride:n-propanol (1:1, v/v). Limits of detection and quantification were 1.50 and 5.00ng/mL, respectively. The assay was linear within the concentration range of 5.00-1000.0ng/mL and the correlation coefficient was R2≥0.993 for both analytes. Absolute recovery was determined at three quality control concentration levels and was found to be at least 87.2% for both substances. Intra-day and inter-day accuracy values for both hydroxyzine and cetirizine were ranged from -1.2 to 3.8% and -2.7 to 2.0%, respectively, at the three concentration levels studied, whereas their respective intra-day and inter-day precision values were less than 9.9 and 6.5%, respectively, in terms of relative standard deviation (%RSD). The developed method was successfully applied for the quantification of hydroxyzine and cetirizine concentrations in whole blood, during the investigation of clinical cases where these two antihistamines were detected.

Metabolites replace the parent drug in the drug arena. The cases of fonazepam and nifoxipam.

Fonazepam (desmethylflunitrazepam) and nifoxipam (3-hydroxy-desmethylflunitrazepam) are benzodiazepine derivatives and active metabolites of flunitrazepam. They recently invaded the drug arena as substances of abuse and alerted the forensic community after being seized in powder and tablet forms in Europe between 2014 and 2016. A review of all the existing knowledge of fonazepam and nifoxipam is reported, concerning their chemistry, synthesis, pharmacology and toxicology, prevalence/use, biotransformation and their analysis in biological samples. To our knowledge, fonazepam and nifoxipam-related intoxications, lethal or not, have not been reported in the scientific literature. All the available information was gathered through a detailed search of PubMed and the World Wide Web.

Bioanalysis of antihistamines for clinical or forensic purposes.

Antihistamines are a class of drugs that inhibit the action of histamine and are used to alleviate symptoms associated with allergic reactions, but some of them can cause side effects, the most unpleasant and dangerous of which are the sedative effects that may hinder important psychological functions and impair skilled performance. These side effects could decrease safety in certain common and critical tasks, such as driving or operating machinery, leading to accidents. Antihistamines can also cause intoxications, sometimes lethal, especially when co-administered with alcohol or other sedative drugs. Thus, the development of analytical methods for their determination in biological fluids is considered to be useful for the investigation of clinical and forensic cases. These methodologies could also be used for pharmacokinetic studies. Several liquid and a few gas chromatographic methods have been developed for the determination of antihistamines in biological matrices after proper pretreatment procedures. This article reviews the published analytical methodologies that were gathered through the search in PubMed database and the recent developments on isolation or determination of antihistamines in biological materials. Current trends and future perspectives on bioanalysis of antihistamines are also discussed. Copyright © 2016 John Wiley & Sons, Ltd.

Recurrent episodes of life-threatening vasodilatory shock following unintentional intoxication with amlodipine.

Calcium channel blockers (CCBs) have a narrow therapeutic index, and their intake in excess is associated with a critical clinical presentation of sustained hypotension and non-cardiogenic pulmonary edema, which are difficult to treat. Unfortunately, the available treatments fail to resuscitate a significant number of patients poisoned by CCBs, rendering them the main cardiovascular drugs involved in death due to overdose. Importantly, in all cases reported until now in the literature, CCB intoxication was known at the time of patients' presentation and the medical challenge solely consisted of the therapeutic approach. In this case report, we describe our experience in treating a 72-year-old patient with recurrent episodes of sustained hypotension refractory to crystalloid and vasoconstrictor infusions. Prolonged pharmacologic support and intermittent sessions of hemofiltration induced stabilization and recovery. The results of an extensive diagnostic workup to elucidate the cause were unfruitful. The recurrent and paroxysmal nature of the clinical presentation along with its incidence after the patient left the protected setting of the hospital led the diagnostic approach to search for a possible external factor, which was shown to be, after toxicological investigation, unintentional amlodipine intoxication.

Fenethylline (Captagon) Abuse - Local Problems from an Old Drug Become Universal.

Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon.

Redefining Vascular Anatomy of Posterior Tibial Artery Perforators: A Cadaveric Study and Review of the Literature.

INTRODUCTION: Perforator flaps whether in a free or pedicled form are essential in leg reconstruction, requiring meticulous dissection based on a detailed understanding of vascular topographic anatomy. Numerous investigators have addressed this issue. However, the directionality of their fascial exit has not been greatly discussed in the literature. Subfascial course of the perforating vessel is a crucial determinant for optimal perforator selection especially when the propeller perforator flap option is considered, because an angulated fascial penetration would eventually result in perforator kinking which would additionally compromise vascular patency. The aim of the current study was to investigate the vascular anatomy of posterior tibial artery evaluating a wide range of parameters, including perforators' subfascial directionality, to precisely determine constant reliable perforator sites, in relation to surface landmarks on the medial aspect of the lower leg. MATERIAL AND METHODS: Dissections in 30 lower legs from 25 fresh cadavers were performed. The lower leg was divided into 3 equal vascular zones. Measurements were taken in reference to anatomical landmarks. Perforator clusters to 5-cm intervals from medial malleolus were recorded and analyzed. Vessels with external diameter less than 0.5 mm were excluded. Data regarding the number, distribution, type, external diameter, length from posterior tibial artery, distance, and subfascial directionality were collected and treated. RESULTS: A total of 155 perforators were identified (average number, 5 per leg; average diameter, 1.0 mm). Septocutaneous (127/155) perforators predominated, followed by musculocutaneous (19/155) and septomusculocutaneous (9/155). Most was concentrated in the middle (73/155) and distal (64/155) tertile. There were no septomusculocutaneous perforators at the distal third of the leg, whereas septocutaneous perforators were encountered into all vascular tertiles. An average of 2 comitant veins accompanied each perforator. Length and diameter related to the perforators' location. There was a significant association between perforator length and type. Cluster analysis revealed that reliable perforators were identified within the 21 to 25, 26 to 30, and 16 to 20 cm intervals. CONCLUSIONS: Clinically optimal perforators for the first time were precisely located in relation to subfascial directionality, vascular diameter, and length from the source artery. Continuous improving details of vascular anatomy will further evolve perforator flaps' applications.

Development and validation of a LC/MS method for the determination of Δ(9)-tetrahydrocannabinol and 11-carboxy-Δ(9)-tetrahydrocannabinol in the larvae of the blowfly Lucilia sericata: Forensic applications.

In a number of forensic toxicological cases, Δ(9)-tetrahydrocannabinol (THC) and its metabolite 11-carboxy-delta-9-tetrahydrocannabinol (THCA) are frequently considered as contributor factors to the event. To that, a liquid chromatographic mass spectrometric method is described for the identification and quantitation of THC and its metabolite THCA in the forensically important larvae of L. sericata. Larvae of Lucilia sericata were fortified with varying concentrations of THC and THCA covering the calibration range between 10 and 500pg/mg. For the isolation of the analytes from larvae, several extraction techniques were evaluated and finally liquid-liquid extraction under acidic pH was selected using hexane-ethyl acetate (50:50, v/v) as extraction solvent. For the chromatographic separation, a Waters Symmetry® C18 analytical column was used while the mobile phase was acetonitrile-ammonium acetate (2mM) (30:70, v/v). The detection was performed using electrospray ionization source in negative mode (ESI-) and the selected ions monitored were m/z 313 for THC and m/z 343 for THCA. The proposed method which is simple and sufficiently sensitive for the detection of THC and THCA even in a single larva sampling, assisted the investigation of a forensic case.

AH-7921: the list of new psychoactive opioids is expanded.

AH-7921 is a structurally unique synthetic opioid analgesic that has recently entered the drug arena in Europe, the USA, and Japan. Although it was synthesized and patented in the mid-1970s, it was first identified in a seized sample purchased via the Internet in July 2012 and formally brought to the attention of the European Union early warning system in August 2012 by the United Kingdom. Several in vitro experiments and animal model studies established the morphine-like analgesic action of AH-7921 as a µ-opioid receptor agonist that has been found to be several times more potent than codeine and at least as potent as morphine. This novel psychoactive substance has already led to eight non-fatal intoxications and 16 deaths in Sweden, the United Kingdom, Norway, and the USA. Thus, AH-7921 is a current public health risk, and better international collaboration, effective legislation and continuous community alertness are needed to tackle this current growing problem. The aim of this review is to summarize the current knowledge about this drug concerning its chemistry, pharmacology, and toxicology, as well as its international legal status. The limited existing analytical methodologies for the determination of AH-7921 in biological samples are also presented. Published or reported AH-7921-related cases, fatalities, or intoxications, and self reports from drug users are reviewed.