Buprenorphine deaths confirmed by toxicology reveal a low proportion of opioid agonist treatment before death in Finland.

We studied opioid agonist treatment (OAT) status before buprenorphine-related death in Finland, where buprenorphine is the principal OAT medicine and also the most misused opioid, through a retrospective population-based study using medico-legal cause-of-death investigation and OAT patient records. The study included all death cases (N = 570) between 2018 and 2020 with a buprenorphine or norbuprenorphine finding in post-mortem toxicology and with known drug misuse history or concomitant findings of illicit drugs. Of the deceased, 10% had received OAT in the year before death. Less than 1% of individuals < 25 years had received OAT, whereas the proportion in individuals ≥ 25 years was 13% (p < 0.001). There were significantly more females and more fatal poisonings (p < 0.001) among those < 25 years than among those ≥ 25 years. OAT medication at the time of death was sublingual buprenorphine-naloxone in 74% and subcutaneous buprenorphine in 23%. Except for significantly fewer benzodiazepine findings among those receiving OAT, minimal differences were found in terms of age, gender, cause and manner of death, or concomitant substance use between the deceased in and outside of OAT. Concomitant misuse of benzodiazepines, psychostimulants, alcohol, and gabapentinoids was frequent both in and outside of OAT and likely contributed to the death. These results suggest that access to OAT especially for young people and treatment of multiple addictions should be improved. Comprehensive information from medico-legal cause-of-death investigation as a starting point, combined with subsequent ante-mortem patient records, proved to be a successful approach to shed light on the Finnish scene of buprenorphine mortality.

Prediction model for anabolic androgenic steroid positivity in forensic autopsy cases - a new tool to the autopsy room.

Non-prescription use of anabolic androgenic steroids (AAS) is associated with an increased risk of premature death. However, these substances are seldom screened in connection with forensic cause-of-death investigation, unless the forensic pathologist specifically suspects use, often based on a positive AAS use history. Since AAS use is often concealed from others, this practice may lead to mistargeting of these analyses and significant underestimation of the true number of AAS positive cases undergoing forensic autopsy. Thus, more accurate diagnostic tools are needed to identify these cases. The main objective of this study was to determine, whether a multivariable model could predict AAS urine assay positivity in forensic autopsies. We analyzed retrospectively the autopsy reports of all cases that had been screened for AAS during forensic cause-of-death investigation between 2016-2019 at the Finnish Institute for Health and Welfare forensic units (n = 46). Binary logistic regression with penalized maximum likelihood estimation was used to generate a nine-variable model combining circumferential and macroscopic autopsy-derived variables. The multivariable model predicted AAS assay positivity significantly better than a "conventional" model with anamnestic information about AAS use only (area under the receiver operating characteristic curve [AUC] = 0.968 vs. 0.802, p = 0.005). Temporal validation was conducted in an independent sample of AAS screened cases between 2020-2022 (n = 31), where the superiority of the multivariable model was replicated (AUC = 0.856 vs. 0.644, p = 0.004). Based on the model, a calculator predicting AAS assay positivity is released as a decision-aiding tool for forensic pathologists working in the autopsy room.

Association of anabolic androgenic steroid use with perimortem polypharmacy, antemortem prescription drug use, and utilization of health care services - A Finnish triple register study of forensic autopsy cases.

Anabolic androgenic steroid (AAS) use has previously been associated with complex polysubstance use that may increase morbidity and mortality among these individuals. In this study we aimed to further describe the features of perimortem polysubstance use, antemortem central nervous system (CNS) drug use and health care service utilization of AAS using males that suffer premature death. The main sample included all cases that were screened for AAS in connection with forensic autopsy between 2016-2019 and tested positive (n = 16). The control samples included autopsy cases that were screened for AAS but tested negative (n = 30) and randomly selected, age and sex matched autopsy cases not suspected of having used AAS but were otherwise fully toxicologically investigated (n = 43). Postmortem toxicological results were used for perimortem polysubstance use prevalence and severity estimation. Antemortem CNS drug use was calculated from a national register of reimbursed prescription medicines, and health care utilization from public health care registers, covering the last five years of life. Perimortem polysubstance use was prevalent in all groups, but the AAS positive had a tendency for greater CNS drug polypharmacy and the highest number of antemortem CNS drug purchases during the last five years of life, with a median of 14.5 purchases/person, vs. 1/person in the AAS negative and 0/person in the random group (Kruskal-Wallis H test, p < .001). Yearly medical contacts increased in all groups as death approached. Our findings suggest that prescription CNS drug use may play a significant role in polysubstance use disorders of AAS using males that suffer premature death.

Comparison of poisoning deaths with wastewater-based consumption estimates and assessment of fatal toxicity for amphetamine-type stimulant drugs.

Among several established indicators that are used to monitor the illicit drug scene, drug-related deaths and wastewater-based epidemiology (WBE) stand out for population-level coverage. In this study, we aimed to compare temporal trends with respect to amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA) revealed by these indicators and explore the differences in fatal toxicity between the stimulants. All deaths in which poisoning caused by amphetamine, methamphetamine or MDMA was either the underlying or contributing cause of death in Finland in 2012, 2014, 2016, 2018 and 2020 were included in the study. Consumption of the studied drugs was measured by WBE in the same years. There was a significant correlation between poisoning and drug consumption for all three stimulants, and for amphetamine and MDMA, these figures increased over the study period. The highest fatal toxicity, as expressed by the number of deaths per million doses, was obtained for methamphetamine at an estimated dose of 50 mg, followed by MDMA (100 mg dose) and with amphetamine (50 mg dose). The fatal toxicity found here for the stimulants was close to that previously reported for many prescription opioids and tricyclic antidepressants. Our study is the first to quantitatively investigate the fatal toxicity of amphetamine-type stimulants by comparing deaths with consumption estimates derived from WBE. It shows that amphetamine, methamphetamine and MDMA possess a quite similar capacity to cause death. This new approach adds to the earlier methods of estimating drug-related harm.

Fatal concentrations of antidepressant and antipsychotic drugs in postmortem femoral blood.

Antidepressants and antipsychotics are both an important class of prescription drugs within postmortem (PM) toxicology because most of the substances are toxic in overdose and the mental disorders being treated may be associated with suicidality. A wide range of antidepressants and antipsychotics are currently included in up-to-date PM toxicology analysis protocols. However, apart from case studies, few reports on fatal concentrations based on large number of cases have been published in the literature. Based on PM investigations in Finland between 2000 and 2020, this study provides fatal reference concentrations in poisonings due to an antidepressant or an antipsychotic drug assigned as the principal intoxicant. Summary statistics for drug concentrations in PM femoral blood (min, max, mean, 10th, 25th, 50th, 75th, 90th percentile) were calculated for 17 antidepressant (N = 2,007) and for 12 antipsychotic drugs (N = 1,161). The proportion of suicide, accident and undetermined manner of death is indicated for each drug. Further, the fatal concentrations obtained in this study were evaluated by comparison with fatal and "normal" PM concentrations reported by two previously published approaches, the grouped causes of death approach and the all causes of death approach, respectively. This study shows that, despite the well-known variation in PM drug concentrations, competently generated fatal concentration results for the drugs studied are consistent to such an extent that they can be used as a reference in the interpretation process.

Ethylene glycol poisoning may be associated with elevated post-mortem vitreous glucose level.

Ethylene glycol (EG) is a toxic chemical that is sometimes used as ethanol substitute. Besides the desired intoxicating effects, the intake of EG may often lead to death unless timely treatment measures are provided by medical professionals. We examined 17 fatal EG poisonings between 2016 and March 2022 in Finland in terms of forensic toxicology and biochemistry results and demographic information. Most of the deceased were male and the median (range) age was 47 (20-77) years. Of the cases, 6 were suicides, 5 accidents and in 7 cases the intent remained undetermined. In all cases, vitreous humour (VH) glucose was above the limit of quantitation 0.35 mmol/L (mean: 5.2 mmol/L; range 0.52-19.5 mmol/L). Other markers of the glycaemic balance were within the normal range in all except one case. As EG is not routinely screened for in most laboratories but only analysed in cases where the intake of EG is suspected, some fatal EG poisonings may remain unrecognised in post-mortem (PM) investigations. Although various conditions may induce hyperglycaemia, it is worthwhile keeping in mind that elevated PM VH glucose levels that cannot be otherwise explained may suggest intake of ethanol substitutes.

Postmortem concentrations of ropivacaine, bupivacaine, and lidocaine in femoral venous blood after hip fracture surgery.

Pain relief in hip fracture patients may be sought by injecting local anesthetic such as ropivacaine, bupivacaine, and lidocaine to the femoral area. As femoral veins are a routine sampling site for postmortem blood, this short report aimed to describe the levels of local anesthetics in ipsilateral (i.e., side of surgery) and contralateral (i.e., opposite side) femoral blood in ten medico-legal autopsy cases that had undergone a hip fracture surgery within 7 days before death. Postmortem blood samples were systematically collected from the ipsilateral and contralateral femoral veins, and toxicological analysis was performed in an accredited laboratory. The sample comprised six female and four male decedents who died at the age of 71-96 years. Median postoperative survival was 0 days and median postmortem interval 11 days. Strikingly, ropivacaine concentration was a median of 24.0 (range 1.4-28.4) times higher on the ipsilateral than contralateral side. The median ipsilateral concentration of ropivacaine clearly exceeded the 97.5th reference percentile measured in this laboratory for ropivacaine in postmortem cases representing all causes of death. The remaining drugs did not show high concentrations or notable differences between the sides. Our data clearly advise against performing postmortem toxicology on femoral blood from the operated side; the contralateral side may constitute a better sampling site. Toxicology reports that are based on blood collected from the operated area should be interpreted with caution. Larger studies are needed to confirm the findings, with accurate records of the dosage and administration route of local anesthetics.

Post-mortem oxycodone blood concentrations of hospitalized cancer and surgery patients compared with fatal poisonings.

Oxycodone is a strong opioid drug commonly used to treat acute, cancer, and chronic non-malignant pain. In this study, all oxycodone-related medico-legal cases where death had occurred in a hospital or nursing home in Finland were investigated to determine the range of post-mortem (PM) oxycodone blood concentrations in a therapeutic setting. All toxicology cases in which oxycodone was detected in PM femoral blood during the 4-year period of 2016-2019 in Finland were retrieved from the national PM toxicology database. In this material, the 365 deceased hospital patient cases that met the study inclusion criteria were divided into four groups according to the cause and manner of death. The reference group of 121 fatal oxycodone poisoning cases comprised two groups: those with verified associated drug abuse and those without drug abuse. The median oxycodone concentration in PM blood was significantly higher in cancer patients (0.10 mg/L) than in patients with recent surgery (0.07 mg/L) or other disease (0.06 mg/L) (p < 0.05). In addition, the median oxycodone concentration was significantly lower in all hospital patient groups than in the poisoning groups, the latter displaying 0.38 mg/L (abuse) and 0.64 mg/L (no abuse) (p < 0.001). This study shows that half of the subjects in the cancer patient group had PM blood oxycodone concentrations above the typical clinical therapeutic plasma concentration range (0.005-0.10 mg/L). Appropriate medication of hospitalized surgery and cancer patients can result in concentrations of up to 0.2 and 0.6 mg/L, respectively, while higher concentrations are exceptional.

Investigation of buprenorphine-related deaths using urinary metabolite concentrations.

Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine poisoning. In this study, 247 autopsy urine samples, previously testing positive for buprenorphine or norbuprenorphine, were quantitatively reanalysed with a recently developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unconjugated buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their respective conjugated metabolites, buprenorphine glucuronide (BUPG), norbuprenorphine glucuronide (NBUPG), and naloxone glucuronide (NALG). The cases were divided, according to medical examiners' decision, to buprenorphine poisonings and other causes of death. The groups were compared for urinary concentrations and metabolite concentration ratios of the six analytes. All median concentrations were higher in the buprenorphine poisoning group. The median concentration of BUPG was significantly higher and the median metabolite ratios NBUP/BUP, NBUPG/BUPG, and NBUPtotal/BUPtotal were significantly lower in poisonings than in other causes of death. Naloxone-related concentrations and ratios were not significantly different between the groups.

Propranolol and metoprolol: Two comparable drugs with very different post-mortem toxicological profiles.

Propranolol is a widely used beta-blocker mainly prescribed for the treatment of hypertension and other cardiac conditions. This medicine is also a frequent finding in drug screens, but little is known about its post-mortem toxicological profile. Our aim was to examine all post-mortem toxicology cases positive for propranolol in a three-year period, between 2016 and 2018 in Finland, and to compare these cases to those positive for metoprolol, another beta-blocker commonly used to treat cardiac diseases. There were 179 cases positive for propranolol and 416 for metoprolol in the study period. In the majority of propranolol cases (53%), the drug concentration in the blood was above the typical therapeutic range, but among the metoprolol cases this proportion was 18%. Propranolol was significantly more common than metoprolol in fatal poisonings, suicides and in cases with a history of drug abuse. Alcohol, benzodiazepines, antipsychotics and antidepressants were significantly more often detected in propranolol cases than in metoprolol cases. The deceased positive for propranolol were significantly younger than those positive for metoprolol. Cardiovascular diseases as the underlying cause of death were significantly more common among the metoprolol cases than among the propranolol cases. Our results showed significant differences between the propranolol group and the metoprolol group in post-mortem toxicology cases. The two drugs were used by two very different groups of people, with propranolol use being associated with psychiatric conditions.

Pregabalin and gabapentin in non-opioid poisoning deaths.

Post-mortem findings of gabapentinoids have often been connected to drug abuse and especially opioid use. We aimed to investigate whether gabapentinoids have been implicated in the cause of death without the presence of opioids. In a three-year study period from 2016 to 2018, a total of 907 Finnish post-mortem cases positive for pregabalin or gabapentin were found. In nearly half of the pregabalin cases and in a third of the gabapentin cases, the blood concentration was above the typical therapeutic range of the drug. Of the cases in which pregabalin was detected, in 35% the drug was implicated in a fatal poisoning with or without other drugs or alcohol. For gabapentin, the percentage was 22%. In most of the fatal gabapentinoid poisonings, opioids or other central nervous system depressants were additionally detected in relevant concentrations. There were eight non-opioid gabapentinoid poisonings, in which no relevant other drugs were detected. Many of these cases were unintentional poisonings with a relatively high gabapentinoid concentration in the blood. In all but one, the manner of death was accidental, or the intent was undetermined. This study confirmed the previous findings that gabapentinoids are mostly implicated in fatal poisoning together with opioids. Half of the non-opioid cases were related to drug abuse but in the other half the death was presumably caused by overuse of a prescribed drug or suicide. While the use of gabapentinoids is a well-known problem among people who use drugs, it is important to note other groups of users who may be at risk of overdose by gabapentinoids.

Trends in MDMA-related mortality across four countries.

AIMS: To determine trends in 3,4 methylenedioxymethamphetamine (MDMA)-related death rates across Australia, Finland, Portugal and Turkey and to analyse the toxicology and causes of death across countries. DESIGN: Analysis of MDMA-related deaths extracted from a national coronial database in Australia (2001-19) and national forensic toxicology databases in Finland (2001-17), Portugal (2008-19) and Turkey (2007-17). Presentation of MDMA use and seizure data (market indicators). SETTING: Australia, Finland, Portugal and Turkey. CASES: All deaths in which MDMA was considered by the forensic pathologist to be contributory to death. MEASUREMENTS: Information collected on cause and circumstances of death, demographics and toxicology. FINDINGS: A total of 1400 MDMA-related deaths were identified in Turkey, 507 in Australia, 100 in Finland and 45 in Portugal. The median age ranged from 24 to 27.5 years, and males represented between 81 and 94% of the deaths across countries. Standardized mortality rates significantly increased across all four countries from 2011 to 2017 during a period of increased purity and availability of MDMA. The underlying cause of death was predominantly due to drug toxicity in Australia (n = 309, 61%), Finland (n = 70, 70%) and Turkey (n = 840, 60%) and other causes in Portugal (n = 25, 56%). Minorities of all deaths across the countries were due to MDMA toxicity alone (13-25%). These deaths had a significantly higher blood MDMA concentration than multiple drug toxicity deaths in Australia, Finland and Turkey. Drugs other than MDMA commonly detected were stimulants (including cocaine, amphetamine and methamphetamine) (Australia 52% and Finland 61%) and alcohol (Australia 46% and Portugal 49%). In addition to MDMA toxicity, benzodiazepines (81%) and opioids (64%) were commonly identified in these deaths in Finland. In comparison, synthetic cannabinoids (15%) and cannabis (33%) were present in a minority of deaths in Turkey. CONCLUSIONS: Deaths related to 3,4 methylenedioxymethamphetamine (MDMA) increased in Australia, Finland, Portugal and Turkey between 2011 and 2017. Findings show MDMA toxicity alone can be fatal, but multiple drug toxicity remains more prevalent.

Increase in drugs-of-abuse findings in post-mortem toxicology due to COVID-19 restrictions-First observations in Finland.

A lot has been published on the anticipated effects of the current COVID-19 pandemic on users of illegal drugs. In this study, we present evidence-based data on such effects, namely, the increased number of drug findings in post-mortem investigations. All post-mortem toxicology cases positive for at least one of the following: buprenorphine, amphetamine or cannabis, were investigated in the first 8 months of the year 2020, and the monthly numbers were compared to those in the previous 5 years from 2015 to 2019. These substances served as indicator analytes that could reveal changes in the drug using population. Right after the government restrictions came into force in March 2020, the numbers of buprenorphine, amphetamine and cannabis findings increased. The increase was most noticeable for amphetamine and was evident in all age groups. Our findings indicate that the assumptions on the increased risk of drug-related harm (including death) have become reality. Reduced access to harm-reduction services seems to have increased the mortality among individuals that use buprenorphine, amphetamine or cannabis. Significant and prompt actions need to be taken in order to find new ways in helping this vulnerable group of people.

Concomitant drugs with buprenorphine user deaths.

BACKGROUND: Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. METHODS: All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. RESULTS: There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years. CONCLUSIONS: The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.

Death in Sauna Associated With a Transdermal Fentanyl Patch.

We present a case of an accidental fatal fentanyl overdose caused by increased uptake of the drug from a transdermal patch while experiencing the heat of a sauna.The transdermal patch administers fentanyl at a relatively constant rate through the skin. However, in the subcutaneous tissue, blood circulation greatly influences the rate of this drug's systemic intake. In the present case, an elderly woman with multiple health conditions was prescribed fentanyl patches but was unaware of the risks associated with external heat sources when one wears the patch. She was found dead in the sauna with a postmortem femoral blood concentration of fentanyl that was elevated (15 µg/L). The cause of death was determined to be fatal poisoning by fentanyl with the contributing factor of external heat from the sauna.Risks associated with transdermal administration of a potent opioid-like fentanyl are widely described in the scientific literature and described in the manufacturer's summary of product characteristics. Physicians and pharmacists should take particular care to ensure that patients understand these risks.

Fatal α-PVP and amphetamine poisoning during a sauna and autoerotic practices.

We describe the sudden death of a middle-aged man while having a sauna under the influence of α-pyrrolidinovalerophenone (α-PVP) (PM blood concentration: 0.8 mg/L), amphetamine (0.34 mg/L), and other drugs (buprenorphine, benzodiazepines), and engaging in solitary sexual activities. The drugs' effects on the cardio-circulatory system and on body thermoregulation combined with the high temperatures are likely to have been central mechanisms leading to death. The high levels of adrenaline triggered by sexual arousal and the respiratory depression caused by buprenorphine, in association with benzodiazepines, may have also contributed to his death. This previously unreported type of accidental autoerotic death illustrates the risk of using amphetamine-like sympathomimetic drugs (e.g. cathinone derivates) in hot environments such as a sauna, and during sexual activities therein.

Femoral blood concentrations of flualprazolam in 33 postmortem cases.

Flualprazolam is a novel designer benzodiazepine, structurally related to alprazolam, flubromazolam and triazolam. In the last couple of years, it has been frequently detected in seizures and in forensic cases in Sweden and Finland. However, there is a lack of published blood concentrations for the drug, which presents difficulties when assessing its relevance for the cause of death. A quantitative method for the determination of flualprazolam in post-mortem blood was developed and validated, and subsequently used to analyse samples from 33 deaths previously screened as testing positive for flualprazolam in Sweden and Finland. Most of the cases in the study were accidental deaths (61 %) or suicides (18 %). The median (range) flualprazolam concentration was 18.0 (3.0-68) ng/g. The majority of the deceased were male (82 %) and the median age was 30 years. The median age in the Swedish cases was significantly higher (35 years) than in the Finnish cases (23 years) (p< 0.05). Poly-drug use and particularly the concomitant use of flualprazolam and opioids were very common in the study population. Most of the cases that were positive for flualprazolam were fatal poisonings by a drug (N=23), and in 13 cases, flualprazolam was implicated in the cause of death. Combining the resources of two countries in which all post-mortem toxicology is centralised provided a more comprehensive insight into the toxicology of flualprazolam. Research on novel psychoactive substances, such as flualprazolam, is required in order to be able to provide scientific evidence on the risks of these new substances for drug administration and potential users.

Significant decrease in the rate of fatal alcohol poisonings in Finland validated by blood alcohol concentration statistics.

BACKGROUND: Alcohol may cause death directly by acute poisoning, as well as induce illnesses or accidents that lead to death. Our research question was whether the current decreasing trend in acute fatal alcohol poisonings in Finland is a real phenomenon or an artefact caused by possible changes in the process of determining the cause of death. METHODS: All cases in the national post-mortem toxicology database in which the underlying cause of death was acute alcohol poisoning in 1987-2018 were investigated in terms of blood alcohol concentration (BAC), age and gender. The number of acute alcohol poisonings was compared to the number of deaths from alcohol induced illness in the post-mortem toxicology database. RESULTS: A total of 12 126 acute alcohol poisoning cases were retrieved. Between 2004 and 2017 the number of acute alcohol poisonings decreased 60.1 %. At the same time the number of alcohol induced illnesses in the study material remained stable or decreased marginally. The median BAC in all acute alcohol poisonings was 3.2 g/kg. The annual median BAC values showed a small but significant decrease over the study period. The proportion of women in acute alcohol poisonings increased significantly over the study period, from 17.1%-22.3%. Women were on average 2.5 years older than men. CONCLUSIONS: On grounds of the BAC statistics and supporting evidence, we conclude that the significant decrease in the number of fatal alcohol poisonings is true and likely reflects changes in the overall consumption of alcohol.

Drug concentrations in post-mortem specimens.

A meta-analysis of drug concentrations in post-mortem specimens is presented. The analysis involved 50 commonly used drugs and their concentrations in femoral blood, other blood (such as cardiac blood), vitreous humor, muscle, liver, kidney, brain, heart, lung, spleen, and bile. A total of 10 993 analytical results from 5375 post-mortem cases in 388 studies were gathered and the ratios of drug concentrations in tissue material to median femoral blood concentrations were calculated. Analytical results from the laboratory's own database (years 2000-2018) were also included. The results show that the variation of ratios between post-mortem specimens and femoral blood is highly compound dependent. This database can be utilized in interpretation of toxicological results in cases where femoral blood is not available. The specimens with similar concentrations as in femoral blood were vitreous humor, muscle, and other blood, such as cardiac blood, and the highest concentrations were generally measured from liver and bile. For these reasons we suggest the following order for biological specimens to be used for a quantitative toxicological analysis in cases where femoral blood is not available: 1. other blood, 2. muscle, 3. vitreous humor, 4. brain, 5. heart, 6. spleen, 7. kidney, 8. liver, and 9. bile.

Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data.

U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance market a few years ago. After incorporating the substance into the urine UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10 autopsy cases within routine case work. In all cases, the cause of death was accidental poisoning by U-47,700 alone or in combination with other psychoactive substances. The concentration of U-47,700 in the blood samples ranged between 0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700 concentration of 0.27 mg/L, no other psychoactive substances were detected. The stored TOF-MS analytical data from the year preceding the incorporation of U-47,700 into the screening was reprocessed in order to search for more positive cases. The data-independent acquisition of the original screening allowed for retrospective re-analysis of the full-scan data without additional experiments on the actual sample. The retrospective data-analysis revealed two additional cases positive for U-47,700. The first mention of U-47,700 on a Finnish internet discussion forum was in March 2015. After having been detected in several death cases, the drug was put under national control in November 2016 and the last fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for approximately 2 years in Finland. Forensic and clinical laboratories need to rapidly adjust their screening procedures in order to adapt to the continuously expanding field of novel psychoactive substances. Retrospective data-analysis is a practical tool for monitoring the emergence of new substances onto the market.