Blood Morphine Research Articles

Electrochemical Detection of Morphine in Untreated Human Capillary Whole Blood.

Disposable single-use electrochemical sensor strips were used for quantitative detection of small concentrations of morphine in untreated capillary whole blood. Single-walled carbon nanotube (SWCNT) networks were fabricated on a polymer substrate to produce flexible, reproducible sensor strips with integrated reference and counter electrodes, compatible with industrial-scale processes. A thin Nafion coating was used on top of the sensors to enable direct electrochemical detection in whole blood. These sensors were shown to detect clinically relevant concentrations of morphine both in buffer and in whole blood samples. Small 38 μL finger-prick blood samples were spiked with 2 μL of morphine solution of several concentrations and measured without precipitation of proteins or any other further pretreatment. A linear range of 0.5–10 μM was achieved in both matrices and a detection limit of 0.48 μM in buffer. In addition, to demonstrate the applicability of the sensor in a point-of-care device, single-determination measurements were done with capillary samples from three subjects. An average recovery of 60% was found, suggesting that the sensor only measures the free, unbound fraction of the drug. An interference study with other opioids and possible interferents showed the selectivity of the sensor. This study clearly indicates that these Nafion/SWCNT sensor strips show great promise as a point-of-care rapid test for morphine in blood.

Heroin overdose masquerades as methomyl poisoning: a case report

BackgroundMethomyl is the most common cause of suicidal death but heroin is the most common cause of accidental death. The problem is to determine the exact cause and manner of death between methomyl or heroin toxicity. The evidence from autopsy includes crime scene investigation, toxicological analysis by liquid chromatography with mass spectrometry, and knowledge of methomyl and heroin intoxication.Case presentationA 35-year-old Thai man and a 30-year-old Thai woman were found showing evidence of cyanosis, with a fine froth around the nose and mouth. Postmortem interval time was 24 hours. According to the police’s and hotel owner’s records, the couple stayed together for 1 day before being found dead in bed, naked, with a foul and a fine froth around the nose and mouth. A methomyl insecticide sachet and a plastic box containing white powder form of heroin were found at the scene. Laboratory tests of the male corpse identified the presence of methomyl in the blood of the stomach and morphine, codeine, methadone, and tramadol in the systemic blood. Blood cholinesterase enzyme activity and morphine concentration was 3416 U/L or 53% (normal 6400 U/L) and 0.058 μg/ml respectively. Laboratory test of the female corpse identified the presence of methomyl in the stomach and blood, and cholinesterase enzyme activity was 1965 U/L or 30.7%.ConclusionsCause of death of the male corpse was deemed to be due to heroin intoxication as the blood concentration of morphine was more than the lethal concentration with a morphine/codeine ratio of more than 1:1. Methomyl intoxication of the male corpse was unlikely to be the cause of death because methomyl systemic blood concentration was found to be very low, < 2.5 μg/ml, and cholinesterase enzyme levels did not indicate lethal activity (< 10–15% of normal). The main problem regarding an insurance claim is that the policy will not pay out in the case of heroin-associated deaths, as it is an addictive drug. The policy would pay out on death by suicide with methomyl insecticide, which was not prohibited by the insurance company after 1 year of insurance. So, it is not clear whether or not the family will receive money from the insurance company.

Detection and identification of morphine in blood of male white rats (rattus norvegicus) by ultraviolet-visible spectrophotometry

The blood of male white rats has been experimentally characterized by Ultraviolet-visible (UV-Vis) Spectrophotometry. Ultraviolet-visible (UV-Vis) spectrophotometry appears as an affordable option to monitor morphine composition in blood of male white rats (Rattus norvegicus). Morphine compounds were identified following two different methods, namely qualitative and quantitative methods. Qualitative analysis of this research by the marquis test and quantitative analysis with spectrophotometry method. The male white rats (Rattus norvegicus) received morphine and it was maintained drug free for 10 days. After that, the blood was taken from the male white rats (Rattus norvegicus) and were extracted the blood using organic solvents, namely methanol and chloroform (1: 1). In the extraction process was used sonication (42 KHz) at temperature 500°C. The qualitative test proves the presence of morphine content with respective concentrations of 1%, 2%, 3%, 4% and 5%. Furthermore, identification of ultraviolet-visible (UV-Vis) spectrophotometry showed that morphine levels in each subcutaneous, that is 0%; 0.6%; 1.0%; 1.6% and 3.5%. The percent transmittance on each samples are 99.9%; 76.9%; 68.8%; 55.9% and 31.0%. The successful application of this simple methodology to a blood of male white rats (Rattus norvegicus) suggests that this approach has practical utility for confirming the identity of abused drugs like morphine detected by ultraviolet-visible (UV-Vis) spectrophotometry.

Morphine in Plasma and Cerebrospinal Fluid of Patients Addicted to Opiates Undergoing Surgery: High-performance Liquid Chromatography Method.

BackgroundThe prevalence of opium addiction among Iranians is considerable. Since endogenous opioid systems may be altered as a consequence of addiction, it is very important to determine the plasma and cerebrospinal fluid (CSF) levels of morphine in Iranian patients addicted to opiates who will undergo surgery.MethodsWe obtained CSF and plasma samples from 50 volunteers with an established opioid addiction pattern. Samples were analyzed using high-performance liquid chromatography (HPLC). Additionally, frequency of nausea and vomiting, baseline heart rate (BHR), and systolic blood pressure (SBP) were recorded within the surgery and postoperatively during a 10-min interval.Findings84% of participants were men with a median age of 39.08 years. Mean score of body mass index (BMI) was 23.30 and most of the participants (46%) used opium in its traditional inhaled form. A higher concentration of morphine in blood was found in comparison with CSF (P < 0.001) in relation to the way of use. However, no statistically significant differences were found in relation to the type of addictive substance. No other association was found between the levels of morphine and the clinical characteristics of the patients. Moreover, results revealed no difference between hemodynamic-related data with blood and CSF level in opium-dependent patients.ConclusionQuantification of plasma and CSF morphine, both immediately before initiation of surgery and subsequently on recovery room, showed that although clinical efficacy of systemic morphine was poor in addicted patients, it had no effect on patients’ hemodynamic variable and following complications after surgery.

Morphological and histopathological heart changes in autopsies of heroin abusers

Backround/Aim. Heroin is a semisynthetic opioid that may cause morphological and histopathological changes in heart: ventricular hypertrophy, myocardial fibrosis, hypertrophy of cardiomyocytes, myofibrils contraction band necrosis, loss of myocytes nuclei and cross-striation, perivascular bleeding, inflammatory cells infiltrate. The aim of the study was to show morphological and histopathological heart changes in autopsies of the long-time heroin abusers with positive toxicological analysis for 6-monoacetylmorphine (6-MAM) and morphine in blood and urine. Methods. Retrospective study was done at the Institute of Pathology and Forensic of the Medicine Military Medical Academy in Belgrade between 2010 and 2014 and included forensic autopsies of 27 examinees aged between 18 and 60. Heart ventricles thicknesses was analysed and histopathological myocard findings from processed material stained by hematoxyline-eosine (H&amp;E) and trichrome stains (Masson) were examined. 6-MAM and morphine concentration in blood and urine using high-performance liquid chromatography coupled with photodiode (HPLC-PDA) and ultraviolet (UV) detector were analysed. Results. Heart ventricles thickness was increased in all persons (27/27; 100%) left 1.74 ? 0.17 cm and right 0.6 ? 0.09 cm. Myocardial fibrosis affected 27/27 (100%) of the examined persons including perivascular one in 24/27 (88.89%) and interstitial focal fibrosis in 3/27 (11.11%); hypertrophy of cardiomyocytes was present in 22/27 (81.48%); myofibril contraction band necrosis in 22/27 (81.48%); loss of myocytes nuclei and cross-striation in 10/27 (37.04%); fresh perivascular bleeding in 23/27 (85.19%); focal inflammatory cells infiltrate in 14/27 (51.85%). In toxicological findings, in 27/27 (100%), 6-MAM and morphine were found in urine. Both 6-MAM and morphine in blood were found in 3/27 (11.11%) and only morphine in blood in 16/27 (59.26%) persons subjected to an autopsy. Conclusion. Our results indicate both morphological (left and right ventricle hypertrophy) and histopathological heart changes (myocardial fibrosis, hypertrophy of cardiomyocytes, contraction-band necrosis, loss of myocytes nuclei and cross-striation, fresh perivascular bleeding and focal inflammatory infiltrate) in long-term heroin obusers. These changes are non-specific and could be caused either by long-term heroin abuse or by other factors. Having in mind a lack of medical histories of examined we could not exclude other factors besides long-term heroin abuse as cause of heart changes.

Homicidal Poisoning of Heroin and Estazolam: Autopsy and Pathological Findings, Toxicological Analysis

We reported an unusual homicidal case in which a 40-year-old woman was deceived into drinking a cup of milk that had 72 tablets of estazolam (2mg/tablet) dissolved in, and then being injected heroin aqueous solution on the right deltoid region by the criminal. At autopsy, pinpoint pupils and a new injection site on the right deltoid region were found. The pathologic pictures showed multiple patchy hemorrhages and considerable amounts of foreign amorphous substance with yellow appearance at the injection site. Some double refracting crystals with the forms of Maltese cross, acicular, rhomb or irregular were found by polarizing microscope, which may result from the diluent in heroin such as starch. Toxicological qualitative analysis by gas chromatography mass spectrometry (GC-MS) demonstrated the presence of benzodiazepine and morphine in blood and urine, and heroin in the injector left at scene. Quantitative analysis was also performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), providing the data on distribution of 6-monoacetylmorphine, morphine and estazolam in the woman’s body. And the cause of death was determined to polydrug heroin-related deaths due to the combined poisoning of heroin and estazolam. It taught a lesson that the determination of other drugs, particularly central nervous system depressants in heroin poisoning were quite important in forensic expertise.

Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths.

Fatal alfentanil/morphine mixture: A case report

Summary A 23 year-old man, health care professional, was found dead in the toilets of a local hospital. Medical supplies for injection (syringe, needles) were found near the body at the scene, in a waste. External body examination revealed a single point of injection located at the left elbow crease and the lack of any traumatic injury. During examination, the pathologist collected cardiac blood and urine. These specimens were tested for ethanol, volatiles, pharmaceuticals and drugs of abuse, using headFspace GC/FID and GC/MS, Elisa, LC-DAD, GC/MS and LC/MS/MS. Ethanol tested positive in blood (0.99 g/L) and urine (0.19 g/L). Using a dedicated LC/MS/MS procedure, alfentanil was identified in both blood (19 ng/mL) and urine (25 ng/mL). Morphine was identified in blood, at 36 ng/mL (free morphine) and 39 ng/mL (total morphine). In urine, total morphine concentration was 81 ng/mL. No other drug was detected. Given the ratio (0.92) free morphine to total morphine in blood and the low concentrations of both alfentanil and morphine in urine, it was considered that the death occurred rapidly after drugs administration. The manner of death was considered as acute intoxication of both alfentanil and morphine, in presence of ethanol.

O41: Dark Web shopping: A case report of a cyanide suicide

Abstract We report an uncommon case of a young white man found dead in a hotel room after cyanide poisoning in a context of suicide. Cyanide was apparently ordered on the Deep Web. The purpose of this case is to compare it with a review of literature about cyanide poisoning (clinical facts and epidemiology), toxic deaths in hotel and scientific observations about black-market and illegally-ordered products on the Dark Web. Case report a 28 years old man was found unresponsive in a hotel room by the cleaner around 12.00 pm. The investigations of the crime scene were as follows: a white young man dressed and clean lean, lying on his back in a bed, a farewell letter left on the bedside table, as well as two small plastic bags (around 5×8 cm) and an empty glass containing a lemon slice. Each bag was numbered, one with a “1” and the second with a “2”. A radiological imagery and an autopsy were performed. Bilateral oedematous and congestive lungs and a visceral congestion without any trace of external or internal traumatism were observed. The family revealed the notion of chronic illegal chronic drug abuse and of the potential purchase of a suicide kit on the Dark Web. Toxicological findings Femoral and cardiac blood, vitreous humor, gastric content, urine, hair and bile samples were collected during the autopsy. Toxicological screening was performed for ethanol, drugs, illicit drugs and cyanide in the biological samples and both plastic bags. The toxicological results were positive for morphine in femoral blood (11.4 ng/mL), urine, bile and vitreous humour and for cyanide in femoral blood (7,2 mg/L). Alprazolam traces were detected in all biological samples and dextromethorphan (an antitussive drug) was present in the gastric content. Analysis of both plastic bags could only identify dextromethorphan traces in bag “1”. Discussion Cyanide intoxication can be intentional (suicide or homicide) or accidental (occupational accident, consumption of cyanogenic plants or food), but it is a rare kind of poisoning, reported previously in few cases. Lethal suicide poisoning with cyanide is even more unusual, especially when the drug is shopped and shipped from Internet. In the present case, the concentration of CN- in femoral blood is very high and corresponds unambiguously to a lethal concentration, considering life-threatening intoxications with cyanide are reported in the literature for blood concentrations superior to 1–2 mg/L. It allows to conclude here that the cause of death is asphyxia by cyanide poisoning and the manner of death is suicide. Although cyanide intoxication with clinical and visceral effects and cyanide-related deaths are well-documented, this case report appears somewhat unusual regarding the association of a toxic death in a hotel room through lethal cyanide poisoning with a shipped and pre-manufactured suicide kit shopped on the Deep Web. Dark Web (or Dark Net) is currently better known, especially since the soar of virtual money named “bit coin” has been used on the Deep Web for shopping. The Dark Web is the part of the web without an indexation on conventional internet search engines. To access to that anonymous web, the user has to know the address that he wants to shop on and to use anonymous devices like TOR. In this case report, two arguments are present to suspect that the young man went to those particular websites: first, the high possibility to perform anonymous shopping of cyanide on the Dark Web, and second, the prudence of the sellers (multiple plastic bags, industrial packaging with no drug trace in bags and no reference on the bags). Moreover, the profile of customers of those websites has been previously shown to correspond to males, young (between 20 and 40 yrs), white, heterosexual, employees or students with a preference for MDMA, LSD and cannabis; the present case is in agreement with this aforementioned profile.

Influence of UGT2B7,OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption

Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7, OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine-induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24hr after initiation of analgesia through a patient-controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies found positive for morphine in routine forensic analysis. Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. The dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.

Detection of abused drugs in human blood by using the on-site drug-screening device Oratect® III.

A simple and precise drug screening method was developed for the detection of abused drugs in whole blood by using the Oratect® III device that is usually employed for the detection of drugs in saliva. Whole blood was acidified with phosphoric acid, following which the hemolyzed solution was filtered through the ultrafiltration column Vivaspin 2 Hydrosart®. The filtrate was then tested for the presence of drugs using Oratect III. The detection limit of the device for methamphetamine, amphetamine, morphine, codeine, dihydrocodeine, diazepam, alprazolam, estazolam, and prazepam in whole blood was 125, 125, 50, 50, 50, 25, 60, 15, and 75ng/mL, respectively. The concentration range detected was between therapeutic and toxic drug levels; therefore, the proposed method can be applied for detecting the presence of abused drugs in blood. Our method is a novel, optimized technique for use in forensic laboratories to screen whole blood for drugs of abuse.

Unexpected variation of the codeine/morphine ratio following fatal heroin overdose.

Postmortem samples from 14 cases of suspected heroin overdose were subjected to a preliminary systematic toxicological analysis in order to highlight the presence of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have played a role in the mechanism of death. This analysis unveiled histories of poly-drug use in seven of the cases under investigation. Moreover, the concentrations of morphine and codeine in the brain were also investigated, and the results were compared with the data obtained from the blood specimens. The concentration of morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine was found to be between 85 and 396 ng/g, while the levels of codeine ranged from 11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to 0.619; however, in the brain, the same ratio was found to be between 0.129 and 0.552. In most cases, a significantly higher codeine/morphine ratio was found in the brain, suggesting the accumulation of codeine in brain tissue due its high lipophilicity as compared with morphine.

Does pure robotic partial nephrectomy provide similar perioperative outcomes when compared to the combined laparoscopic-robotic approach?

Laparoscopic and robotic partial nephrectomy have become the preferred option for surgical management of incidentally discovered small renal tumors. Currently there is no consensus on which aspects of the procedure should be performed laparoscopically versus robotically. We believe that combining a laparoscopic exposure and hilar dissection followed by tumor extirpation and renorrhaphy with robotic assistance provides improved perioperative outcomes compared to a pure robotic approach alone. We performed a comparison of perioperative outcomes between combined laparoscopic-robotic partial nephrectomy-or hybrid procedure-and pure robotic partial nephrectomy (RPN). A multi-center retrospective analysis of patients undergoing RPN and hybrid PN using the da Vinci S system(®) was performed. Patient data were reviewed for demographic and perioperative variables. Statistical analysis was performed using the Welch t test and linear regression, and nonparametric tests with similar significance results. Thirty-one patients underwent RPN while 77 patients underwent hybrid PN between 2007 and 2011. Preoperative variables were comparable in both groups with the exception of lesion size and nephrometry score which were significantly higher in patients undergoing hybrid PN. Length of surgery, estimated blood loss and morphine used were significantly less in the hybrid group, while warm ischemia time was significantly longer. The difference in WIT was accounted for in this data by adjusting for nephrometry score. In our multi-center series, the hybrid approach was associated with a shorter operative time, reduced blood loss and lower narcotic usage. We believe this approach is a valid alternative to RPN.

Development and Validation of a New GC-MS Method for the Detection of Tramadol, O-Desmethyltramadol, 6-Acetylmorphine and Morphine in Blood, Brain, Liver and Kidney of Wistar Rats Treated with the Combination of Heroin and Tramadol

Heroin is one of the most dangerous abused drugs in the world. Tramadol is an additive recently found at high concentration levels in street heroin seizures in Egypt. This substance could affect the usual analytical method for the detection of heroin and metabolites, as well as the pharmacokinetic and disposition of single analytes. One shortfall regarding this issue is present in the literature. This study describes a validated, simple, sensitive and selective method to determine tramadol, O-desmethyltramadol, 6-acetylmorphine and free morphine in the blood, brain, liver and kidney of Wistar rats, intraperitoneally treated with a combination of heroin and tramadol (10 and 70 mg/kg, respectively) using liquid-liquid extraction and gas chromatography-mass spectrometry detection. The calibration curves of tramadol, O-desmethyltramadol and 6-acetylmorphine in blood were linear in the concentration range from 25-5,000 ng/mL and morphine was found in the concentration range 50-5,000 ng/mL. The analytes were detected in all tested matrices, except 6-acetylmorphine, which was not detected in liver. The highest concentrations of tramadol and O-desmethyltramadol were observed in kidney (22,9381 and 28,498 ng/g), while 6-acetylmorphine and morphine were found at the highest levels in brain (3,280 and 3,899 ng/g, respectively). The present method is simple, rapid and sensitive and can be used to study the pharmacokinetics, disposition and interaction of these drugs in several animal models.

Validation of a Gas Chromatography–Ion Trap-Tandem Mass Spectrometry Assay for the Simultaneous Quantification of Cocaine, Benzoylecgonine, Cocaethylene, Morphine, Codeine, and 6-Acetylmorphine in Aqueous Solution, Blood, and Skeletal Muscle Tissue

A gas chromatography-ion trap-tandem mass spectrometry method was developed and validated for the simultaneous solid-phase extraction and quantification of cocaine, benzoylecgonine, cocaethylene, morphine, codeine, and 6-monoacteylmorphine in blood, muscle tissue, and water. An assay for total morphine in blood and muscle was also validated. The limit of quantification was ≤ 0.01 mg/kg in muscle and ≤ 0.005 mg/L in blood and water. Good linearity was observed over the concentration ranges studied (r ≥ 0.99). The repeatability (% RSD) at the three concentration levels was typically ≤ 15% and never exceeded 17%. Intermediate precision of ≤ 16% was obtained for all matrices. Deviation < 20% of the nominal concentration was obtained in all repeatability and intermediate precision experiments. Extraction recoveries for cocaine and metabolites ranged from 91% to 110% in water, 81% to 110% in blood, and 61% to 75% in muscle. Recoveries for opiates ranged from 59% to 104% in water, 50% to 95% in blood, and 41% to 79% in muscle. The hydrolysis efficiency for the total morphine assay in blood and muscle ranged from 91% to 99% with within-day and intermediate precisions of ≤ 14% and ≤ 12%, respectively.

Morphine to codeine concentration ratio in blood and urine as a marker of illicit heroin use in forensic autopsy samples

A morphine to codeine ratio greater than unity (M/C>1) has been suggested as an indicator of heroin use in living individuals. The aim of this study was to examine the morphine to codeine ratio in a large population (N=2438) of forensically examined autopsy cases positive for 6-monoacetylmorphine (6-MAM) and/or morphine in blood and/or urine. Blood and urine concentrations of 6-MAM, morphine and codeine were examined using GC-MS and LC-MS/MS methods. In 6-MAM positive samples, the M/C ratio was greater than unity in 98% (N=917) of the blood samples and 96% (N=665) of the urine samples. Stratification of 6-MAM negative cases by M/C above or below unity revealed similarities in morphine and codeine concentrations in cases where M/C>1 and 6-MAM positive cases. Median blood and urine morphine concentrations were 8-10 times greater than codeine for both groups. Similarly to 6-MAM positive cases, 25-44 year-old men prevailed in the M/C>1 group. In comparison to cases where M/C ≤ 1, the M/C ratio was a hundred times higher in both 6-MAM positive and M/C>1 cases. The range of morphine concentration between the lowest and the highest quintile of codeine in M/C>1 cases was similar to that in 6-MAM positive cases. This range was much higher than for M/C ≤ 1 cases. Moreover, linear regression analyses, adjusted for age and gender, revealed a strong positive association between morphine and codeine in 6-MAM positive and M/C>1 cases. The M/C ratio appeared to be a good marker of heroin use in post-mortem cases. Both blood and urine M/C>1 can be used to separate heroin users from other cases positive for morphine and codeine.

Heroin poisoning deaths with 6-acetylmorphine in blood: demographics of the victims, previous drug-related offences, polydrug use, and free morphine concentrations in femoral blood

This article discusses cases of drug-poisoning death in which 6-acetylmorphine (6-AM) was identified in blood as evidence for recent use of heroin. We report the demographics of the victims, previous drug-related offences, polydrug use, and the concentrations of free morphine in peripheral blood. After solid-phase extraction, morphine, codeine, and 6-AM were determined in blood samples by isotope-dilution gas chromatography–mass spectrometry (GC–MS) using limits of quantitation of 0.005 mg/l for each opiate. The victims of heroin poisoning were mainly men (88%), with a mean age of 35.4 ± 8.4 years (±SD) and no significant gender difference in age (men 35 ± 8.4 years; women 35 ± 8.6 years). The median concentration of free morphine in blood (n = 671) was 0.25 mg/l (66% > 0.20 mg/l) and women had a higher concentration (0.30 mg/l) than men (0.24 mg/l) (P 0.05) was found for the concentration of free morphine in blood when heroin was the only drug taken (median 0.26 mg/l, n = 53) compared with multidrug deaths (median 0.24 mg/l, n = 618) (P > 0.05). The coingested drugs most commonly identified in heroin-related deaths were ethanol (44%), diazepam (27%), cannabis (20%), and flunitrazepam (19%). We found that 61% of victims had previous drug-related offences ranging from 1 to 48 times. The close agreement between the concentrations of free morphine in blood when heroin was the only drug taken and multidrug deaths suggests that differences in tolerance to opiates is more important in causing death than adverse drug–drug interactions.

Validation of the Abbreviated Westmead Post-traumatic Amnesia Scale: A brief measure to identify acute cognitive impairment in mild traumatic brain injury

Objective: To validate the use of the Abbreviated Westmead Post-traumatic Amnesia Scale (A-WPTAS) in the assessment of acute cognitive impairment in mild traumatic brain injury (mTBI).Methods: Data previously collected from 82 mTBI and 88 control participants using the Revised Westmead Post-traumatic Amnesia Scale (R-WPTAS) was converted to A-WPTAS scores and pass/fail classifications were calculated for both scales.Results: The proportion of failures on the R-WPTAS and the A-WPTAS did not differ and a similar number of mTBIs were classified on each. For mTBIs the relationship between the independent memory test and a pass/fail classification was the same for both scales. Bivariate logistic regressions revealed that mTBIs, relative to controls, were around 8 times more likely to fail the assessment (R-WPTAS: 95% CI: 3.70–18.87; A-WPTAS: 95% CI: 3.70–20.14). As verbal learning improved the likelihood of failure was reduced. Greater education was associated with a decreased likelihood of failure. The relationship between education and a fail performance was not sustained when education was adjusted for the effect of age, prior mTBI, blood alcohol level, injury status, verbal learning, and morphine administration.Conclusions: The A-WPTAS is a valid measure. The A-WPTAS may reduce the risk of failing to classify patients with mTBI by identifying and documenting acute cognitive impairment.

Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice

High blood-brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6-monoacetylmorphine (6-MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6-MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6-MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The estimated metabolic rate of heroin in brain was much lower and cannot account for the low heroin and high 6-MAM levels in the brain, which would primarily reflect the concentrations of these compounds in blood. The very different metabolic rates for heroin in blood and brain calculated by the model were confirmed by in vitro experiments. These results show that heroin's fast metabolism in blood renders high concentrations of 6-MAM which, due to its relatively good blood-brain permeability, results in high levels of this metabolite in the brain. Thus, it is the high blood metabolism rate of heroin and the blood-brain permeability to 6-MAM, and not to heroin, which could account for the highly efficient delivery of active metabolites to the brain after heroin administration.

Error in the Article: "Driving Under the Influence of Opiates: Concentration Relationships Between Morphine, Codeine, 6-Acetyl Morphine, and Ethyl Morphine in Blood"

Error in the Article: "Driving Under the Influence of Opiates: Concentration Relationships Between Morphine, Codeine, 6-Acetyl Morphine, and Ethyl Morphine in Blood"