Blood Morphine Concentration Research Articles

Morphine concentrations in fatalities after palliative treatment of acute burn injury

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.

Developing mathematical models to compare and analyse the pharmacokinetics of morphine and fentanyl.

The two-compartment model is generally used in pharmacokinetics to illustrate the distribution and excretion of drugs. In this study, we evaluated the distribution patterns of morphine and fentanyl by using a two-compartment model. Using numeric analysis techniques, non-linear ordinary differential equations were used to mathematically analyse drug distribution, transition, and concentration in the body compartments. Math Works, Inc., MATLAB, version 2023a, a programming tool, was used to characterise the impact of initial concentration and rate constants on the kinetics of the drug. For a definite therapeutic concentration of morphine and fentanyl in blood, pharmacokinetic characteristics were plotted. The study results showed the time taken by morphine and fentanyl to reach a target concentration in the blood that is sufficient to generate the preferred therapeutic effects. The mathematical models comparing morphine and fentanyl pharmacokinetics showed that fentanyl reached the target therapeutic concentration 125 minutes earlier than morphine and was metabolised and removed from the body more rapidly (44 minutes earlier than morphine). These comparative mathematical models on morphine and fentanyl enable the determination of drug dosages and understanding of drug efficacy that facilitates optimising dosing regimens. The right choice between them can be made based on the time to reach the target therapeutic concentration in the blood, elimination time, severity of pain, and patient characteristics.

The systematic investigation of the role of adulterants into the postmortem redistribution of heroin

We aimed to investigate systematically the impact of adulterants on postmortem in vivo pharmacokinetic of heroin and its metabolites by determining the postmortem redistribution (PMR) of heroin in this study. Heroin (1 mg/kg) was administered intravenously to the rats. The rats were euthanized 1 hour after drug administrations, followed by placed in the supine position at room temperature. Femoral (right and left), subclavian, cardiac blood samples and liver, lung, kidney, myocardium and brain samples were collected at the time of death, postmortem 1st, 4th and 24th hour. Heroin (1 mg/kg) containing adulterants (1 mg/kg paracetamol, dextromethorphan and caffeine) was administered intravenously to the same number of rat groups, and the same procedures were repeated. All blood and organ tissue samples were analysed with validated liquid-liquid extraction methods using a liquid chromatography tandem-mass spectrometer. The changes in the levels of heroin metabolites during the postmortem interval were determined in different blood and tissue samples included in our study. Accordingly, apart from the minimal statistical differences in morphine concentrations in the left femoral blood, significant differences in each matrix throughout the postmortem interval, especially in heart blood, lung and kidney tissue were observed. In contrast to morphine, there are minimal differences in morphine-3-glucurinide concentrations in heart tissue and other matrices. Graphical differences were observed between morphine concentrations in heart blood, liver, myocardium and lung of animal groups in the presence of adulterants and animal groups in which heroin was administered alone. The findings obtained in this study may play an important role in elucidating heroin-related death cases by forensic toxicologists or pathologists.

Correlation study between anatomopathological data and levels of blood morphine concentrations in heroin-related deaths.

Heroin-related mortality is a complex phenomenon involving several factors that make an individual more susceptible to opioid toxicity. Among these, pre-existing pathological conditions play an important role. The current paper reviewed 51 autopsied cases performed over the last 30years, each subject ("frequent heroin user") having taken heroin intravenously alone before death. For each case, total blood morphine concentration determined by gas chromatography-mass spectrometry (GC-MS) was obtained from the archives. For histopathological evaluation we examined microscopic sections of the heart, lung, brain, liver and kidney, and for each organ a score table with a numerical value from 1 to 5, as an indicator of increasing severity, was drawn up. Finally, we created a scoring system based on the Injury Severity Score (ISS), generated by the sum of the squares of the three highest organ scores. We investigated the relationship between total blood morphine value (mg/l) and pathological score by inserting the two variables in a linear regression model: Score=a+b·Morphinemia (p-value <0.001). The results demonstrated a statistically significant correlation between the two variables: individuals with low total blood morphine values tended to have a higher pathological score. Our study provides useful assessment tools for forensic practice, confirming the need to combine two important disciplines in drug death investigation: forensic pathology and toxicology.

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.

Significance of Morphine Concentration in Bile, Liver, and Blood: Analysis of 52 Cases of Heroin Overdoses.

Forensic pathologists are requested to select matrices alternative to blood in cases of toxicological interest in which blood is not available for different reasons. We evaluated morphine concentrations in blood, bile, and liver samples in 52 cases of heroin overdoses, relating them to each other, to understand the information that could be derived from their analysis. Gas chromatography/mass spectrometry analysis was performed for all the samples positive on screening for opiates. Shapiro-Wilk test, nonparametric Mann-Whitney test, linear regression analysis, and Bland-Altman test were used for analysis. Linear regression demonstrated that there was not a statistically significant association in morphine concentrations between blood and bile and blood and liver. Mean liver/blood ratio was 2.76, varying from 0.131 to 13.379, and bile/blood ratio was 28.79, varying from 0.28 to 559.16. According to these results, bile analysis is a "screening test"; biliary or hepatic concentration of morphine cannot provide information on hematic concentration at the time of death, having no forensic value taken individually.

In silico (computed) modelling of doses and dosing regimens associated with morphine levels above international legal driving limits

Background: Morphine can cause central nervous system side effects which impair driving skills. The legal blood morphine concentration limit for driving is 20 µg/L in France/Poland/Netherlands and 80 µg/L in England/Wales. There is no guidance as to the morphine dose leading to this concentration. Aim: The in silico (computed) relationship of oral morphine dose and plasma concentration was modelled to provide dose estimates for a morphine plasma concentration above 20 and 80 µg/L in different patient groups. Design: A dose–concentration model for different genders, ages and oral morphine formulations, validated against clinical pharmacokinetic data, was generated using Simcyp®, a population-based pharmacokinetic simulator. Setting/participants: Healthy Northern European population parameters were used with age, gender and renal function being varied in the different simulation groups. In total, 36,000 simulated human subjects (100 per modelled group of different ages and gender) received repeated simulated morphine dosing with modified-release or immediate-release formulations. Results: Older age, women, modified-release formulation and worse renal function were associated with higher plasma concentrations. Across all groups, morphine doses below 20 mg/day were unlikely to result in a morphine plasma concentration above 20 µg/L; this was 80 mg/day with the 80 µg/L limit. Conclusion: This novel study provides predictions of the in silico (computed) dose–concentration relationship for international application. Individualised morphine prescribing decisions by clinicians must be informed by clinical judgement considering the individual patient’s level of impairment and insight irrespective of the blood morphine concentration as people who have impaired driving will be breaking the law. Taking into account expected morphine concentrations enables improved individualised decision making.

Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis.

We investigated the in vivo dynamics and analgesic effect of morphine using an adjuvant-induced arthritis (AA) rat as a model of chronic inflammation. Morphine generally binds to μ-opioid receptors in the brain to exert its effects. After several minutes, it is metabolized by glucuronidation via a UDP-glucuronosyltransferase (UGT). Here, we showed that in AA rats, UGT activity in liver microsomes was reduced. Morphine-free serum fractions in AA rats were also decreased (control, 84.9%; AA, 63.9%) and the expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), which plays a crucial role in morphine bile excretion, decreased to 23.0% that of the control group. However, we observed no significant difference between the AA and control groups regarding blood concentrations of morphine and morphine-3-glucuronide. In contrast, the analgesic effect of morphine increased 4-fold in AA rats. Our results showed that the pharmacokinetics of morphine is not changed, but the pharmacodynamics of morphine is enhanced in chronic inflammation.

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.

Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: Detection and quantitation a case series from early 2017

BackgroundSynthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). MethodsCases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry. Results25 post mortem cases in which synthetic fentanyl analogues were implicated in the cause of death were reported from January to May 2017. No cases were seen in June 2017. The age range was 21–54 years and 22 were male. There was a history of heroin use, or markers of heroin use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13 cases, with the remaining 5 cases having only carfentanil present. Synthetic fentanyl analogues were detected in combination with other drugs in all cases. Significant concentrations of ethanol were detected in only 2 cases. The concentration range of carfentanil in blood was 90–4004pg/mL. Of note, the 3 cases in which ante mortem carfentanil was quantified ranged from 21 to 98pg/mL. In all cases, death was attributed to combined central nervous system depression. ConclusionsThis paper highlights a new and rapid emergence of these drugs into the UK illicit drug arena. Synthetic fentanyl analogues represent a significant challenge both analytically and clinically within the groups who misuse drugs. It is worthwhile considering the possibility of the presence of these drugs in cases in which a toxicological cause of death is not apparent analytically but there is a history of drug use and circumstantial evidence exists to support a drug-related death as the most likely cause. It may be that synthetic fentanyl analogues should be screened for routinely to avoid reporting any false negative results, but the cost implications and viability of this have not been fully evaluated.

Physical Dependence and Plasma Concentrations of Morphine in Rats

It is very important to set an appropriate dose level and frequency with a sufficient duration of administration to allow for assessment of the physical dependence liability of drugs. The purpose of this study was to investigate the relationship between the physical dependence liability and blood concentrations of morphine following an oral administration. Morphine was administered by oral gavage once daily for 28 days at dose levels of 10 and 30 mg/kg/day, and then withdrawal signs were observed for 7 days. During the withdrawal period, apparent withdrawal signs such as hyper reactivity to handling, loose stools, piloerection and transient, statistically significant decreases in the percent change of body weight gain and food consumption were noted at 30 mg/kg/day. At 10 mg/kg/day, hyperreactivity to handling and piloerection were observed, but transient decreases in the percent change of body weight gain and food consumption were not noted. The mean plasma concentrations of morphine at 24 h post-dosing at 10 and 30 mg/ kg/day were 3.4 and 13.6 ng/mL on Day 1 of dosing and 3.91 and 20.3 ng/mL on Day 28 of dosing, respectively. The plasma concentrations of morphine at 30 mg/kg/day were above the lower limit of the effective blood concentrations in humans. Thus, it was suggested that dose levels that can maintain effective blood concentrations or higher in humans should be selected for evaluation of physical dependence liability.

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida.

In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 mg/L, respectively. In the heroin cases with fentanyl present (n=7), the average free morphine concentration was 0.040 mg/L, the average total morphine concentration was 0.080 mg/L, and the average fentanyl concentration was 0.012 mg/L. In the cases with heroin, fentanyl, and acetyl fentanyl (n=3), the average free morphine concentration was 0.010 mg/L, the average total morphine concentration was 0.030 mg/L, the average fentanyl concentration was 0.018 mg/L, and the average acetyl fentanyl concentration was 0.008 mg/L. In the cases involving only acetyl fentanyl (without heroin or fentanyl, n=4), the average acetyl fentanyl concentration was 0.47 mg/L and the average acetyl norfentanyl concentration was 0.053 mg/L. The presented cases, with associated drug concentrations, case histories, demographics, and causes and manners of death may help provide assistance with the interpretation of the postmortem findings. Based on case circumstances, autopsy results, and toxicology results, it is evident that fentanyl and/or acetyl fentanyl, when present, contributed to the cause of death.

Fatal oral heroin overdose. A case report

Overdose by heroin injection is well-known but overdose by swallowing is poorly described. A case of lethal overdose by heroin ingestion is presented. A 25-year-old man prisoner was found hanged in his retention unit, he occupied alone, with feet based on the floor. He was seen alive 90 minutes before death. An autopsy was performed four days later and initially, concluded by mechanical asphixya death, without fight or injection marks. Toxicology analysis were realized on peripheral blood, bile and gastrointestinal contents and results are described. Alcohol dosage was realized by GC-FID on all samples. Blood and gastric liquid screening was realized by GC-MS and LC-MS/MS, after liquid/liquid extraction in acidic and basic conditions. Specific methods by GC-MS or LC-MS/MS were done for cannabinoids, amphetamines, cocaine and opiates determination. Other identified substances were quantified by LC-MS/MS or immunoassay. Alcohol was not found in any sample. Concerning drugs of abuse, only opiates were detected in blood and liquid gastric. Morphine, 6-MAM and codeine were measured in concentration of 996 μg/L, 366 μg/L and 84 μg/L in peripheral blood and 45 μg/g, 152 μg/g and 25 μg/g in liquid gastric respectively. Heroin was also detected at 25 μg/g in liquid gastric in association with papaverine and noscapine (opium alkaloids). Some prescribed drugs as tramadol and paracetamol were also identified at 472 μg/L and 42 mg/L in blood. The presence of heroin intact in liquid gastric, without injection marks on the body, suggest oral absorption. After the present first toxicologic results, the food found in the unit was analyzed by the Forensic Police National Institute (INPS) and heroin was detected in a piece of cake, confirming the route of administration. The prisoner was not known to consume heroin. The presence of 6-MAM in blood after oral administration of heroin suggests a massive and recent absorption before the death, probably greater than 1 gram [1]. Indeed, several publications showed that after an ingested dose lower than 1 gram, neither heroin nor 6-MAM could be detected in blood due to a very high activity of deacetylation systems in either the gut or the liver or both [1]. Blood concentrations of morphine and 6-MAM measured were potentially lethal, in particular for a naive subject, by inducing a respiratory depression. However, it was not possible to conclude if the death was related to the heroin overdose or to the hanging, probably a mixed process.

Study of the Ratio between Morphine-3-β-D-Glucuronide and Morphine-6-β-DGlucuronide in Blood Samples from Heroin Fatalities

In heroin fatalities the diagnosis of the cause of death, based only on chemical and toxicological data, may be particularly difficult; a complete knowledge of the case history is fundamental. Thus, for each case analytical results should be interpreted taking into account also autopsy findings, information from the scene and relevant medical history. In fact wide variability is present in post-mortem blood concentration of morphine (MOR), the main metabolite of heroin, which is usually the most important analytical result for the interpretation of the cause of death. Recently, increasing interest has grown towards the role of the metabolites morphine-3-β-D-glucuronide (M3G) and morphine-6-β-D-glucuronide (M6G) in mediating heroin effects. To this purpose SPE technique was employed to extract MOR, M3G and M6G from autopsy blood samples. Subsequently a LC/MS-MS method for the determination of these analytes was developed, using a gradient elution with a binary mobile phase, the analytes being revealed by means of an ESI-QqQ Mass Spectrometer operating in positive ionization and MRM mode. After validation, the method was applied to twenty-one blood specimens collected from cases of suspected acute narcotism which previously underwent a Systematic Toxicological Analysis (STA) to highlight the presence of ethanol and of the main drugs of abuse and/or their metabolites. The concentration ratios of MOR, M3G and M6G were investigated. The influence of some risk factors, such as the contemporary use of alcohol, methadone or cocaine, was also studied. Some important indications emerged: the ratio M3G/M6G, being quite constant, should be a valid reference value to assess toxicity. Furthermore the value of M3G/M6G ratio detected in heroin addict, in this study, is lower than that found in people who assume morphine for therapeutic purposes. This ratio could be of help to overcome the difficult interpretation of chemical and toxicological data.

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.

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.

Wither codeine?

Wither codeine?

Comparison of serum and lithium‐heparinate plasma for the accurate measurements of endogenous and exogenous morphine concentrations

Comparison of serum and lithium‐heparinate plasma for the accurate measurements of endogenous and exogenous morphine concentrations

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.

Evaluating the Relationship Between Postmortem and Antemortem Morphine and Codeine Concentrations in Whole Blood

The purpose of this study was to examine the relationship between antemortem (AM) and postmortem (PM) morphine and codeine concentrations in whole blood. In addition, the effects of antemortem to death interval as well as the postmortem interval were considered during the interpretive process. The cases of seven human subjects are presented here with an average postmortem interval of 28 h (13.5-48 h) and an average antemortem to death interval of 97 min (ranging from 9 to 300 min). Drug concentrations were obtained from AM blood collected from local hospitals in Miami, FL, and postmortem blood was obtained from the Miami-Dade County Medical Examiner Department in Miami, FL. The results obtained for this study indicated that factors such as metabolism and postmortem interval can affect postmortem drug concentrations in an unpredictable manner. Four out of seven morphine cases appeared to be affected by postmortem redistribution, and five of seven codeine and two of two 6-monoacetylmorphine cases were affected as well.