Postmortem Redistribution Research Articles

The Determination of Insulin Overdose in Postmortem Investigations.

The analysis of biological specimens for the presence of exogenous insulin is of special interest in select postmortem investigations. Insulin analogues are primarily used to mediate the regulation of blood glucose concentrations; however, their use has also been implicated or suspected as a cause of death in suicides, accidents, and homicides. Toxicological analysis for these compounds is challenging due to the large molecular weight, the limited stability of insulin in whole blood, and complexities associated with sample preparation and instrumental testing. As a consequence, determination of insulin in postmortem specimens is not routinely offered by most forensic toxicology laboratories. Forensic death investigation is further complicated by interpretative difficulties such as the frequent absence of anatomical findings, concentration interpretation in known insulin users, and addressing the impact of chemical instability and postmortem redistribution. There are ongoing efforts, however, to develop and validate robust methods that may be used for this analysis on these challenging samples and that are capable of withstanding scientific and legal scrutiny for forensic use. In this regard, in recent years, methods for the detection of exogenous insulin in postmortem samples have been reported and results of this testing has been published in a handful of cases. The purpose of this article is to review the primary functions of insulin, the disease states associated with the therapeutic use of exogenous insulin, the current state of laboratory testing, and to provide case summaries that summarize the timeline of advancements and underscore the importance of this work.

Rotenone Analysis by Liquid Chromatography–Tandem Mass Spectrometry with Information-Dependent Acquisition in a Fatal Case of Rotenone Poisoning with a Commercial Organic Insecticide Being Sold in Korea

Rotenone is a neurotoxin derived from Derris roots or yam bean of genus Derris or Lonchocarpus It is known to cause Parkinson-like symptoms and is a potent electron transport inhibitor. Rotenone was detected in postmortem specimens in a fatal case of rotenone poisoning with an organic pesticide by liquid chromatography-tandem mass spectrometry with an information-dependent acquisition and MS-MS library search. The forensic specimens were prepared by solid-phase extraction with a Bond Elut(®) Certify cartridge. The mobile phase comprised 5 mM ammonium formate in 10% methanol and 5 mM ammonium formate in 90% methanol. The assay was linear over the range from 0.01 to 1.0 mg/L (r(2) = 0.995). The limit of detection and quantitation in the blood were 0.001 mg/L (signal-to-noise, S/N = 3) and 0.003 mg/L (S/N = 10), respectively. The intraday accuracy and precision for rotenone that were determined by five replicates at 0.02, 0.10 and 1.0 mg/L in blood were <15.0% of bias and <9.0% of CV, respectively. The interday accuracy and precision for rotenone that were determined by seven replicates at 0.02, 0.10 and 1.0 mg/L in blood were <18.0% of bias and <17.0% of CV, respectively. Relative recovery with 0.02, 0.1 and 1.0 mg/L in blood was 104.2, 103.3 and 81.6% (n = 6), respectively. The described method was applied for the determination of rotenone in a fatal case of intoxication of a 33-year-old man who was found dead on a bed in a temporary house. In this case study, the concentrations of rotenone in heart blood (HB), peripheral blood (PB), gastric contents and vitreous humor were 0.77 mg/L, 0.02 mg/L, 126.4 mg/kg and 0.003 mg/L, respectively. The rotenone concentration ratio of the HB/PB was 38.8 and that of gastric contents/PB was 6412.3, suggesting a massive ingestion of rotenone with postmortem redistribution. This study is the report of rotenone detection in a fatal case with the ingestion of the organic insecticide containing rotenone.

Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases

For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites.

Postmortem redistribution mechanism of donepezil in the rat

Population aging is rapidly advancing in numerous parts of the world and, accordingly, the prevalence of Alzheimer's disease (AD) is rising. The safety of donepezil (DPZ), which is used for AD treatment, has been established in clinical trials. However, some studies have indicated that DPZ may be associated with severe cardiac side effects, and excessive doses may induce toxicity-related symptoms or death. Therefore, the measurement of blood DPZ levels is important for the postmortem investigation of related causes of death. However, postmortem drug concentrations in the blood may not always reflect those obtained antemortem because of the postmortem redistribution (PMR) of drugs. Therefore, the aim of this study was to investigate the potential PMR of DPZ using a rat model. The DPZ concentration was measured using a validated HPLC/Q-TOF-MS system in cardiac and peripheral blood, and in the brain, lungs, myocardium, liver, and thigh muscle at different postmortem intervals (0, 1, 3, 6, 12, and 24h). Overall, the DPZ tissue to peripheral blood ratio decreased throughout the postmortem period. Furthermore, the DPZ concentration increased in the peripheral and cardiac blood but decreased in both of the lungs, postmortem. Furthermore, the blood pH was significantly lowered. We used a perfusion approach to examine the rat lung and heart to further investigate the relationship between the pH and DPZ release from the lungs. The outflow concentrations when the inflow pH changed from 7.4 to 5.5 were approximately 2-fold higher than the inflow pH fixed 7.4. These findings suggest that the antemortem accumulated DPZ in the lungs is released into the pulmonary blood owing to postmortem acidification of blood, and subsequently flows into the cardiac blood, leading to the observed increase in concentration. Although we could not determine the underlying mechanism, we confirmed that PMR occurs similarly in the cardiac and peripheral blood.

Gabapentin concentrations and postmortem distribution

Gabapentin is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. Gabapentin has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional self-poisonings, serious effects are generally rare. In this report, gabapentin analyses were performed on 30 postmortem cases that had peripheral blood, central blood and liver tissue. Overall the central to peripheral blood (C/P) ratio mean was 0.90±0.24 (mean±standard deviation), and a median of 0.97. The liver to peripheral blood (L/P) ratio mean was 0.68±0.26L/kg (mean±standard deviation), and a median of 0.65L/kg. An additional case, where both antemortem blood and postmortem peripheral blood specimens were available, revealed the same gabapentin concentration in both specimens. Taken together, the data presented suggests that gabapentin is unlikely to show postmortem redistribution.

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine.

Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.

Postmortem blood concentrations of sartans measured by liquid chromatography-tandem mass spectrometry

A liquid chromatography-tandem mass spectrometric (LC–MS/MS) method was developed and validated for the analysis of seven common sartans (candesartan, eprosartan, losartan, olmesartan, telmisartan, valsartan, and losartan carboxylic acid (EXP3174), the active metabolite of losartan) in postmortem blood samples with liquid–liquid extraction. Detection was accomplished by triple-quadrupole MS in the selected reaction monitoring mode. The validation procedure showed low limits of quantitation of 5 ng/mL for all compounds with good accuracy and precision. The matrix effect was evaluated from the variation of peak areas and concentrations. The method shows some matrix effect but the effect was efficiently compensated by using an internal standard method. The method was applied to the analysis of sartans in postmortem blood samples, and produced 534 positive findings during 2014–2015. Nine deaths were encountered where the concentration of a sartan was very high, indicating intoxication together with other causes of death or multi-drug intoxication. The quantitative results indicate that sartans do not show significant postmortem redistribution; thus concentrations higher than the therapeutic range can be considered as being toxic or fatal.

Analytical data in support of the liver and peripheral blood concentration (L/P) ratio as a marker of postmortem redistribution

Analytical data in support of the liver and peripheral blood concentration (L/P) ratio as a marker of postmortem redistribution

Postmortem redistribution of methamphetamine and amphetamine in blood specimens from various blood vessels and in the specimens from pericardial fluid, bile, stomach contents and various solid tissues collected from a human cadaver

We recently encountered an autopsy case in which methamphetamine (MA) was involved. The postmortem interval was estimated to be as long as 6–7 days. We collected the blood specimens from 9 locations of the heart and blood vessels, and specimens from pericardial fluid, bile, stomach contents and 9 solid tissues (in total 21 specimens), which were subjected to analysis of MA and the metabolite amphetamine by liquid chromatography–tandem mass spectrometry after a modified QuEChERS extraction. The highest concentration of MA was found for the stomach contents, suggesting the oral ingestion of MA. Among the blood specimens, their MA concentrations varied from 268 to 911 ng/mL. The concentration of MA in the left heart blood was higher than that in the right heart blood. In spite of this, the MA concentration in the pulmonary vein was much lower than that in the left heart blood. The comparison of MA concentrations in venous blood vessels showed that MA concentration was highest in the vena cava, followed by the iliac vein, and was lowest in the femoral vein, suggesting that MA concentration is decreased by diffusion across the thin walls of venous blood vessels during the postmortem interval. The partial loss of a xenobiotic by diffusion via the thin wall of the femoral vein should be taken into consideration especially when the postmortem interval is relatively long.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

Postmortem redistribution of olanzapine following intramuscular administration of olanzapine pamoate in dogs

The potential for postmortem redistribution of olanzapine was investigated in beagle dogs. Olanzapine pamoate monohydrate was administered once every 14 days by intramuscular injection for 3 months to fed male dogs (n=15) at a dose of 20mg/kg olanzapine (equivalent to 46mg/kg olanzapine pamoate monohydrate). Blood samples were collected after the fifth (Day 57) and sixth (Day 71) doses to determine olanzapine and N-oxide olanzapine concentrations. On Day 71 at 72h postdose, dogs were euthanized and placed on their backs without additional manipulation and held for postmortem blood, urine, and tissue collection at room temperature for up to 168h postdose (96h after euthanasia). Concentrations of olanzapine and N-oxide olanzapine were determined by liquid chromatography–mass spectroscopy/mass spectroscopy (LC–MS/MS). Postmortem olanzapine concentrations in blood increased up to seven-fold compared to the last quantified antemortem blood concentration. Olanzapine concentrations in vein tissue samples (surrogates for peripheral blood) also increased, whereas other tissue concentrations, such as myocardium, lung, liver, and kidney decreased over the postmortem period. An increase in blood concentration of olanzapine after death was observed in all but one animal, suggesting that postmortem redistribution may occur in dogs following biweekly intramuscular administration of olanzapine pamoate monohydrate. The rise in olanzapine concentrations in blood after death in this study may potentially be attributed to diffusion from multiple tissues to blood and, to a lesser extent, reduction of the N-oxide olanzapine metabolite back to olanzapine. However, the generalizability of these results to humans cannot be confirmed by the present study.

Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional (13)C isotope monitoring.

Postmortem redistribution (PMR) is one of numerous problems in postmortem toxicology making correct interpretation of measured drug concentrations difficult or even impossible. Time-dependent PMR in peripheral blood and especially in tissue samples is still under-explored. For further investigation, an easy applicable method for the simultaneous quantitation of over 80 forensically relevant compounds in 11 different postmortem matrices should be developed and validated overcoming the challenges of high inter-matrix and intra-matrix concentration variances. Biopsy samples (20mg) or body fluids (20μL) were spiked with an analyte mix and deuterated internal standards, extracted by liquid-liquid extraction, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). For highest applicability, an easy solvent calibration was used. Furthermore, time-consuming dilution of high concentration samples showing detector saturation was circumvented by two overlapping calibration curves using (12)C isotope monitoring for low concentrations and (13)C isotopes for high concentration, respectively. The method was validated according to international guidelines with modifications. Matrix effects and extraction efficiency were strongly matrix and analyte dependent. In general, brain and adipose tissue produced the highest matrix effects, whereas cerebrospinal fluid showed the least matrix effects. Accuracy and precision results were rather matrix independent with some exceptions. Despite using an external solvent calibration, the accuracy requirements were fulfilled for 66 to 81% of the 83 analytes. Depending on the matrix, 75-93% of the analytes showed intra-day precisions at <20%. (12)C and (13)C calibrations gave comparable results and proved to be a useful tool in expanding the dynamic range.

High-resolution mass spectrometric determination of the synthetic cannabinoids MAM-2201, AM-2201, AM-2232, and their metabolites in postmortem plasma and urine by LC/Q-TOFMS.

High-resolution mass spectrometry and accurate mass measurement by liquid chromatography/quadrupole-time of flight mass spectrometry (LC/Q-TOFMS) was applied to postmortem plasma and urine specimens from an autopsy of a fatal case involving synthetic cannabinoid use, resulting in the detection of three synthetic cannabinoids: MAM-2201, AM-1220, and AM-2232. We searched for their metabolites existing in postmortem plasma or urine by LC/Q-TOFMS and were able to detect N-dealkylated metabolites, defluorinated and further oxidized metabolites of MAM-2201, and some hydroxylated metabolites. Postmortem plasma concentrations of the parent drugs, N-dealkylated metabolites, and fluorinated and further oxidized metabolites of MAM-2201 were measured, and quantitation results revealed site differences between heart and femoral postmortem plasma concentrations of parent drugs and some metabolites, suggesting postmortem redistribution of the synthetic cannabinoids and their metabolites. Quantitation results suggest that defluorination is a major metabolic pathway for MAM-2201, and N-dealkylation is a common but minor pathway for the naphthoylindole-type synthetic cannabinoids in human.

Interpreting postmortem drug analysis and redistribution in determining cause of death: a review

Interpreting postmortem drug analysis and redistribution in determining cause of death: a review

Liquid chromatography with tandem mass spectrometry for the determination of flufenoxuron in blood using automatic solid phase extraction and its application to a fatal case of flufenoxuron poisoning

A liquid chromatography/tandem mass spectrometry method with solid phase extraction for the detection and the quantitation of flufenoxuron in an aliquot of blood was developed and validated. Flufenoxuron belongs to a benzoylurea insecticide and is the active ingredient of Cascade™. The analyte in postmortem specimens was extracted by solid-phase extraction with Bond Elut Certify cartridge. After the elution layer was evaporated, the residue was reconstituted with 70% methanol for LC/MS/MS analysis. Separations were carried out on a Synergi® 2.5u Fusion-RP 100 A column with column temperature kept at 40°C at a flow rate of 0.4mL/min. The mobile phase was composed of 5mM ammonium formate in 10% methanol and 5mM ammonium formate in 90% methanol using gradient elution. A triple quadruple mass spectrometer equipped with an electrospray ionization source operated in a positive ion mode with selective reaction monitoring mode. Atrazine-d5 was used as internal standard. The assay was linear over 0.02–1.0mg/L (r2=0.999). Limit of detection (LOD) and limit of quantitation (LOQ) in blood were 0.009mg/L (S/N=3) and 0.02mg/L (S/N=10), respectively. The accuracy and the precision were <14.9% of bias% and <8.1% of CV%, which are acceptable criteria according to toxicology laboratory guidelines. Relative recoveries with 0.02, 0.1 and 1.0mg/L (in blood) were 112.3%, 101.2% and 111.0% (n=5), respectively. The developed method was applied in forensic toxicology to determine flufenoxuron in postmortem specimens in a fatal case of flufenoxuron intoxication in a 48-year-old-man who was found dead on bed in a small room after vomiting on the floor. The postmortem heart blood, peripheral blood and gastric contents were analyzed for flufenoxuron with the result of 6.3mg/L in heart blood, 3.2mg/L in peripheral blood and 30.6mg/kg in gastric contents, respectively. The concentration ratio of the heart/peripheral blood of flufenoxuron was 2.0, and the ratio of gastric contents/peripheral blood was 9.4, suggesting possible postmortem redistribution and there may be a massive amount of flufenoxuron orally ingested. This case study is the first report of lethal concentrations of flufenoxuron in postmortem specimens.

İlaçların Postmortem Yeniden Dağılımı Toksikolojik Örnek Alma Veri Değerlendirme ve Yorumlama

Postmortem redistribüsyon ölümden sonra ilaç konsantrasyonlarında meydana gelen değişimleri ifade eder. Akciğer, karaciğer ve miyokard gibi organlardan kan içerisine yeniden dağılımı içerir. Postmortem ilaç konsantrasyonları ilacın karakteristik özelliğine ve örneklemenin alındığı bölgeye dayalı olarak varyasyonlar göstermektedir. Dağılım hacmi, lipofilite ve pKa gibi ilaç özellikleri önemli faktörlerdir. Bazik, lipofilik ve 3 l/kg’dan daha büyük dağılım hacmine sahip ilaçların postmortem yeniden dağılıma uğraması muhtemeldir.Kan örneklemenin yapıldığı anatomik bölge ilaç konsantrasyonunu etkileyebilmektedir. Otopside toplanan kan, önemli bir biyolojik örnektir. Kardiyak ve periferik kandan oluşmaktadır. Kardiyak kan konsantrasyonu genelde periferik kan konsantrasyonundan daha yüksektir. Periferik kandaki postmortem ilaç konsantrasyonunun antemortem ilaç konsantrasyonuna benzer olduğu kaydedilmiştir. Bu yüzden ilaçların analizi ve yorumlanması için periferik bölgeden kanın toplanması önerilir. Pek çok laboratuvar postmortem vakalarda yeniden dağılımı tanımlarken kardiyak:periferik kan (C/P) konsantrasyon oranını kullanır. Bu oran birden daha büyük olduğunda o ilacın postmortem yeniden dağılım göstereceği düşünülür. Postmortem ilaç konsantrasyonu dokularda daha stabil olduğundan dolayı karaciğer: periferik kan (L/P) oranı da postmortem yeniden dağılım belirteci olarak değerlendirilir. Postmortem yeniden dağılımın anımsanmasıyla postmortem kanda tespit edilen ilaç konsantrasyonuna güven azalmakta ve doku analizinin önemi yeniden gündeme gelmektedir.Postmortem dönemde ölçülen ilaç konsantrasyonlarını yorumlamak karışıktır. Bu sebeple çalışmamızda “Postmortem redistribüsyon nedir ve toksikolojik verilerin doğru ve güvenilir değerlendirilmesi için hangi biyolojik örnekler alınmalıdır” sorularına yanıtlar literatür ışığında sunulacaktır.Anahtar Kelimeler: İlaç, Postmortem Yeniden Dağılım, Adli Toksikoloji

Post-mortem toxicology: A pilot study to evaluate the use of a Bayesian network to assess the likelihood of fatality

The challenge of interpreting post-mortem drug concentrations is well documented and relies on appropriate sample collection, knowledge of case circumstances as well as reference to published tables of data, whilst taking into account the known issues of post-mortem drug redistribution and tolerance. Existing published data has evolved from simple data tables to those now including sample origin and single to poly drug use, but additional information tends to be specific to those reported in individual case studies. We have developed a Bayesian network framework to assign a likelihood of fatality based on the contribution of drug concentrations whilst taking into account the pathological findings. This expert system has been tested against casework within the coronial jurisdiction of Sunderland, UK. We demonstrate in this pilot study that the Bayesian network can be used to proffer a degree of confidence in how deaths may be reported in cases when drugs are implicated. It has also highlighted the potential for deaths to be reported according to the pathological states at post-mortem when drugs have a significant contribution that may have an impact on mortality statistics. The Bayesian network could be used as complementary approach to assist in the interpretation of post-mortem drug concentrations.

Postmortem distribution of trazodone concentrations

Non-toxic postmortem trazodone tissue (liver) concentrations have not been previously described. Liver trazodone concentrations were compared to peripheral blood and central blood concentrations in 19 medical examiner cases. Postmortem blood specimens were initially screened for alcohol and simple volatiles, drugs of abuse, and alkaline drugs. Trazodone, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a high performance liquid chromatography procedure. Re-analyses showed that there may be degradation of trazodone in postmortem blood stored at 4°C. There was, on average, about a 20% decrease in samples stored up to eight months. These data suggest that postmortem trazodone peripheral blood concentrations may be considered non-toxic to at least 1.0mg/L with liver concentrations to at least 2.2mg/kg. Overall, trazodone concentrations ranged from 0.08–6.1mg/L in peripheral blood, 0.07–7.1mg/L in central blood, and 0.39–26mg/kg in liver. The median trazodone central blood to peripheral blood ratio was 0.98 (N=19). The liver to peripheral blood ratios showed a median value of 2.8L/kg (N=18). Given that a liver to peripheral blood ratio less than 5L/kg is consistent with little to no propensity for postmortem redistribution, these data demonstrate that trazodone is unlikely to show significant redistribution.

Donepezil distribution in postmortem cases and potential for redistribution

Donepezil (DPZ) is an acetylcholine-esterase inhibitor currently used as the frontline drug to treat Alzheimer's disease. The aim of this study was to investigate the possibility of postmortem redistribution (PMR) of DPZ, which could complicate the determination of cause of death in medico-legal cases. Additionally, metabolic enzyme DNA polymorphism, drug–drug interaction and the presence of lesions in metabolic and egestion organs were examined to eliminate the possibility of a high antemortem DPZ concentration. Subsequently, the average DPZ concentration of four sites of peripheral blood (right and left femoral artery and vein) was compared with central blood and liver DPZ concentrations in seven postmortem cases. DPZ concentrations ranged from 0.02 to 0.45μg/mL in the peripheral blood, 0.09–0.4μg/mL in central blood, and from 1.2 to 6.7μg/kg in the liver. In most specimens, the concentrations were higher than the therapeutic range (approximately 0.030–0.075μg/mL). DPZ central blood to peripheral blood (C/P) ratios averaged 1.73±1.02 (±standard deviation) while liver to peripheral blood (L/P) ratios were higher and averaged 17.5±7.25. It is documented that a C/P ratio of less than (or about) 1.0 and an L/P ratio less than 5 are not indicative of PMR, whereas a C/P ratio exceeding 2 and L/P ratio exceeding 20 highlight a propensity for significant PMR. Our data suggest that DPZ exhibits a moderate degree of PMR. Additionally, a lowered pH was found in all blood specimens (<6–6.75 in the peripheral blood and <6–6.66 in the central blood). This postmortem reduction in blood pH may increase the ionic forms of DPZ, resulting in a high blood DPZ concentration.

Striking increases in postmortem compared to antemortem drug concentrations in a suicidal overdose: A case report

Toxicology testing revealed dramatic increases in whole-blood concentrations of verapamil and diphenhydramine in the short time between hospital admission and death (53 min) in a subject (with a history of overdosing) found unresponsive. While some degree of post-mortem redistribution (PMR) would be expected for the drugs found in this case, PMR cannot explain the considerable increases observed. It is recommended that in potential overdose cases without a clear manner of death but for which ante-mortem and post-mortem specimens (including gastric content) are available, all should be analysed and considered in order to make a more definitive conclusion regarding that death.