Postmortem Blood Drug Research Articles

Determination of new psychoactive substances and other drugs in postmortem blood and urine by UHPLC-MS/MS: method validation and analysis of forensic samples.

This study aimed to validate a modified QuEChERS method followed by ultra-high performance liquid chromatography-tandem mass spectrometry to determine 79 new psychoactive substances (NPS) and other drugs in blood and urine. Prescription drugs (n = 23), synthetic cathinones (n = 13), phenethylamines (n = 11); synthetic cannabinoids (n = 8), amphetamines (n = 7) and other psychoactive substances (n = 17) were included in the method. 500 µL of biological fluid was extracted with 2mL of water/ACN (1:1), 500mg of anhydrous MgSO4/NaOAc (4:1) added, followed by a supernatant cleanup with 25mg of primary secondary amine and 75mg of anhydrous MgSO4. Quantification was done using matrix-matched calibration curves and deuterated internal standards. The method was satisfactorily validated for blood and urine at limit of quantifications ranging from 0.4 to 16ng/mL, and applied to the analysis of 54 blood (38 postmortem and 16 antemortem) and 16 antemortem urine samples from 68 forensic cases. All urine samples and 59.3% of the blood samples were positive for at least one analyte. Twenty-two analytes were detected in at least one biological sample, including the synthetic cathinones ethylone (222ng/mL, antemortem blood), eutylone (246 and 446ng/mL, urine), and N-ethylpentylone (597 and 7.3ng/mL, postmortem and antemortem blood, respectively). The validated method was shown to be suitable for the analysis of blood and urine forensic samples and an important tool to collect information on emerging drug threats and understanding the impact of NPS and other drugs in poisoning cases.

Comparing ELISA and LC–MS-MS: A Simple, Targeted Postmortem Blood Screen

A comprehensive screening method that is specific, accurate and customizable is necessary in any forensic toxicology laboratory. Most laboratories utilize some form of immunoassay testing as it is reliable and sensitive with minimal sample preparation and is relatively inexpensive to simultaneously screen for multiple classes of drugs with different chemical properties. However, accessibility to more specific technology and instrumentation such as mass spectrometry has increased and therefore using immunoassay as the screening method of choice may be revisited. A screening method for 42 drugs in postmortem blood was developed and validated following the Organization of Scientific Area Committees for Forensic Science guidelines for toxicology method validation. The method was developed using minimal sample preparation of postmortem blood consisting only of a protein precipitation. Only two internal standards were used, which greatly reduces the cost of implementing this method. Limit of detection, interference studies, processed sample stability and ion suppression/enhancement were examined. Additionally, over 100 case samples were analyzed by both the current enzyme-linked immunosorbent assay (ELISA) testing procedure and the proposed liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening method. The comparison determined that the LC-MS-MS method performed as well as or better than the ELISA in nearly all cases. The ability to add additional target drugs increases the laboratory's scope of analysis as well. This method is ideal for forensic laboratories wishing to improve screening while working within budget constraints.

Just say no to postmortem drug dose calculations.

For years, a number of professional groups have warned forensic and clinical toxicologists against calculating an administered dose of a drug based on postmortem blood drug concentrations. But to date, there has been limited information as to how unreliable these dose calculations may actually be. Using amitriptyline as a model drug, this study used empirically determined pharmacokinetic variables for amitriptyline from clinical studies coupled with clinical overdoses (where the individual survived), and death case studies (ascribed to amitriptyline toxicity) in which the dose of amitriptyline was known. Using these data, standard pharmacokinetic equations, and general error propagation, it was possible to estimate the accuracy of calculated doses of amitriptyline, compared with the doses that were consumed. As was expected in postmortem cases, depending on the pharmacokinetic equation used, the accuracy (mean +128% to +2347%) and precision (SD±383% to 3698%) were too large to allow reliable estimations of the dose of amitriptyline consumed prior to death based on postmortem blood drug concentrations. This work again reinforces that dose calculations from postmortem blood drug concentrations are unreliable.

Simple implementation of muscle tissue into routine workflow of blood analysis in forensic cases – A validated method for quantification of 29 drugs in postmortem blood and muscle samples by UHPLC–MS/MS

Whole blood is most often the matrix of choice for postmortem analysis but it is not always available. In these cases, muscle tissue can be used as an alternative matrix. Therefore, an ultra-high-performance liquid chromatography–tandem mass spectrometry method for the quantification of 29 drugs and metabolites of toxicological interest in postmortem muscle tissue was developed and validated. Additionally, a validation of whole blood was carried out to compare the results from the two matrices. Solid-phase extraction was performed by an automated robotic system to minimize manual labour and risk of human errors, and increase robustness, sample throughput and sample traceability. The method was validated in terms of selectivity, matrix effect, extraction recovery, process efficiency, measuring range, lower limit of quantification, carry-over, stability, precision and accuracy. To correct for any inter-individual variability in matrix effects on analyte accuracy and precision, deuterated analogues of each analyte were used as internal standards. The lower limit of quantification in both blood and muscle homogenate ranged between 0.002 and 0.005 mg/kg, while the upper limit of quantification spanned from 0.20 to 1.0 mg/kg. Corrected with the 4-fold dilution factor, the corresponding concentrations in muscle tissue were 0.008–0.02 mg/kg at the lower limit of quantification and 0.80–4.0 mg/kg at the upper limit of quantification. The method showed acceptable precision and accuracy, with precision below 12% and accuracies ranging from 87% to 115% at up to 6 levels for all analytes in both matrices. In addition, comparison between calibration standards in spiked muscle homogenate and spiked blood showed that analyte concentrations in muscle samples could be quantified by using spiked blood samples as calibration standards with acceptable precision and accuracy when using deuterated analogues as internal standards. The investigation of matrix effects showed no great difference between blood and homogenates of non-decomposed and decomposed muscle tissue for most analytes. In the samples where high ion suppression or enhancement was observed, the results were corrected by the internal standards. Statistical comparison of quality control samples in blood and muscle tissue showed no obvious differences, and therefore muscle tissue was included in the routine method for analysis of blood samples and used in autopsy cases where no blood was available. By adding a semi-automated homogenization step before the remaining automated sample preparation, muscle tissue samples were easily incorporated into the workflow of the existing routine method. The present method has been successfully implemented in routine analysis of blood and muscle tissue since 2019.

Development of a UHPLC-MS/MS method for the determination of 84 pharmaceuticals and drugs of abuse in human liver

Analysis of post-mortem liver for toxicological reasons is a considerable option when blood is unavailable. The development of analytical methods for tissue specimens is not as straightforward as for biological fluids as tissue presents challenges to the analytical chemist. The present study reports the development of a UHPLC-MS/MS method for the detection and quantification of 84 drugs and pharmaceuticals in human liver. The selected target drugs include pharmaceutical drugs and drugs of abuse. Sample preparation was studied using QuEChERS and different ratios of solvent volume and sample mass. Best results were attained by homogenizing 1 g of liver with acetonitrile K2CO3 buffer (pH = 10), QuEChERS salts MgSO4/ NaCl (1st purification step) and PSA/ 150 mg MgSO4 (2nd purification step). The extracted sample was analysed on UHPLC-MS/MS in multiple reaction monitoring mode (MRM) on a reversed-phase (Acquity BEH C18) column. Elution was accomplished by gradient program of mobile phase A: water, 0.1% formic acid and B: methanol, 0.1% formic acid that lasted 17 min. The method was specific, without interferences from the complex matrix. Sensitivity was satisfactory with limit of detection (LOD) ranging from 0.01 ng/g to 4.94 ng/g. Validation study was based on the guidelines of international bodies and included evaluation of recovery, carry-over, matrix effect, accuracy, stability, and precision of the method. The method performed satisfactory in relation to established bioanalytical criteria and was therefore applied to the analysis of liver tissue obtained post-mortem from chronic drug abusers, offering unambiguous identification and quantitative determination of drugs in postmortem blood.

A UHPLC-MS-MS Method for the Determination of 84 Drugs of Abuse and Pharmaceuticals in Blood.

The analysis of blood samples for forensic or clinical intoxication cases is a daily routine in an analytical laboratory. The list of 'suspect' drugs of abuse and pharmaceuticals that should be ideally screened is large, so multi-targeted methods for comprehensive detection and quantification are a useful tool in the hands of a toxicologist. In this study, the development of an ultra-high performance liquid chromatography (LC)-tandem mass spectrometry (MS-MS) method is described for the detection and quantification of 84 drugs and pharmaceuticals in postmortem blood. The target compounds comprise pharmaceutical drugs (antipsychotics, antidepressants, etc.), some of the most important groups of drugs of abuse: opiates, cocaine, cannabinoids, amphetamines, benzodiazepines and new psychoactive substances. Sample pretreatment was studied applying a modified Mini-QuEChERS single step, and the best results were obtained after adding a mixture of 20mg MgSO4, 5mg K2CO3 and 5mg NaCl together with 600μL of cold acetonitrile in 200μL of sample. After centrifugation, the supernatant was collected for direct injection. LC-MS analysis took place on a C18 column with a gradient elution over 17min. The method was found to be selective and sensitive, offering limits of detection ranging from 0.01 to 9.07ng/mL. Validation included evaluation of limit of quantification, recovery, carryover, matrix effect, accuracy and precision of the method. The method performed satisfactorily in relation to established bioanalytical criteria and was therefore applied to the analysis of blood obtained postmortem from chronic drug abusers, offering unambiguous identification and quantitative determination of drugs in postmortem blood.

A comparison of blood toxicology in fatalities involving alcohol and other drugs in patients with an opioid use disorder treated with methadone, buprenorphine, and implant naltrexone

ABSTRACTBackground: Methadone, buprenorphine, and implant naltrexone have comparable efficacy in preventing death from drug intoxication during treatment, but there may be differences between treatments in the specific drugs contributing to death and in the risk of death during different phases of treatment.Objective: The objective of this study was to compare concentrations of individual drugs in decedents for evidence that the three medications use to treat opioid use disorders differed in the protection they offered against fatal overdose.Methods: Fatalities with a primary or co-diagnosis of alcohol or other drug poisoning in patients treated with methadone (n = 66, 74.2% male), buprenorphine (n = 54, 74.1% male), or naltrexone (n = 28, 85.7% male) were identified by combining treatment (Monitoring of Drugs of Dependence System and clinical records) and mortality records (Western Australian Death Registry). Quantitative postmortem blood drug analysis data were obtained for drug-related deaths. The presence/absence of drugs were compared between the three medication groups and between phases of treatment (on-treatment/off-treatment).Results: Opioids (89.8%) and benzodiazepines (76.2%) were most commonly identified in postmortem blood. The three medication groups did not differ materially in the drugs present postmortem, except that alcohol was less prevalent in naltrexone-treated cases. Morphine or heroin intoxication was implicated in more patients dying off-treatment than on-treatment but levels of morphine and other drugs were comparable across the two phases.Conclusion: Comparisons of postmortem concentrations of specific drugs indicated that patients treated with methadone, buprenorphine, and implant naltrexone had comparable susceptibilities to lethal co-intoxication and that similar drug mixtures contributed to death.

Search for fungi-specific metabolites of four model drugs in postmortem blood as potential indicators of postmortem fungal metabolism

Fungi colonizing cadavers are capable of drug metabolism and may thus change the metabolite pattern or concentration of drugs in forensic postmortem samples. The purpose of this study was to check for the presence of such changes by searching fungi-specific metabolites of four model drugs (amitriptyline, metoprolol, mirtazapine, and zolpidem) in decomposed postmortem blood samples from 33 cases involving these drugs. After isolation and identification of fungal strains present in the samples, each isolate was incubated in Sabouraud medium at 25°C for up to 120h with each model drug. One part of the supernatants was directly analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS), another after liquid–liquid extraction with chlorobutane and concentration. From 21 out of 33 decomposed postmortem blood samples (64%) a total of 30 different strains could be isolated, one from the class of Ascomycete and the rest belonging to 15 species from 8 different genera (number of species): Aspergillus (2), Botrytis (1), Candida (8), Fusarium (1), Mucor (1), Penicillium (1), and Rodothorula (1). In the in vitro studies, these microorganisms were found capable of N-demethylation and N-oxidation of amitriptyline and mirtazapine, O-demethylation followed by side chain oxidation of metoprolol as well as hydroxylation of all four-model drugs. In two of the postmortem blood samples, from which the fungi Aspergillus jensenii, Candida parapsilosis. and Mucor circinelloides had been isolated, a fungi-specific hydroxy zolpidem metabolite was detected. The presence of this metabolite in postmortem samples likely indicates postmortem fungal biodegradation.

Analysis of new designer drugs in post-mortem blood using high-resolution mass spectrometry.

An analytical method was developed and validated for the purpose of detecting and quantifying 37 new designer drugs including cathinones, hallucinogenic phenethylamines and piperazines. Using only 100 µL whole blood, a salting-out-assisted liquid-liquid extraction with acetonitrile was performed to isolate target compounds followed by chromatographic separation using a Waters ACQUITY ultra performance liquid chromatograph coupled to a Waters XEVO quadrupole time-of-flight mass spectrometer. Mephedrone-d3 was used as an internal standard. A gradient elution was used in combination with a Waters ACQUITY HSS C18 column (2.1 × 150 mm, 1.8 µm). Samples were analyzed using the detector in positive electrospray ionization mode with MS(E) acquisition. All compounds of interest were resolved in a 15 min run time and positively identified based on accurate mass of the molecular ion, two product ions and retention time. All analyte calibration curves were linear over the range of 0.05-2 mg/L with most correlation coefficient (r(2)) values >0.98. The limits of detection were within the range of 0.007-0.07 mg/L and limits of quantification within 0.05-0.1 mg/L. All analytes were stable 48 h after extraction and most were stable in blood after 1 week stored in a refrigerator and 3 freeze-thaw cycles. No carryover was observed up to 10 mg/L and no interferences from common therapeutic drugs or endogenous compounds. Recoveries ranged from 71 to 100% and matrix effects were assessed for blank, post-mortem and decomposed blood. All bias and % coefficient of variation values were within the acceptable values of ±15 and ≤15%, respectively (±20 and ≤20% at lower limit of quantification). The method was applied to several forensic cases where the subject exhibited behavior characteristic of designer drug intoxication and where routine screening for a panel of drugs was negative.

Simultaneous analysis of 22 antiepileptic drugs in postmortem blood, serum and plasma using LC-MS-MS with a focus on their role in forensic cases.

In recent years, there has been a growth in reports of antiepileptic drugs (AEDs) being misused on their own or in combination with other drugs of abuse in a variety of toxicological case types such as drug abuse, suicide, overdose and drug facilitated crime. To our knowledge, there are no simultaneous quantification methods for the analysis of the most commonly encountered AEDs in postmortem whole blood and clinical plasma/serum samples at the same time. A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed and validated for the simultaneous quantification of carbamazepine (CBZ) and its metabolite CBZ-10,11-epoxide, eslicarbazepine acetate, oxcarbazepine and S-licarbazepine as a metabolite, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, phenobarbital, phenytoin and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, retigabine (ezogabine) and its metabolite N-acetyl retigabine, rufinamide, stiripentol, topiramate, tiagabine, valproic acid, vigabatrin and zonisamide in postmortem whole blood, serum and plasma which would be suitable for routine forensic toxicological analysis and therapeutic drug monitoring. All AEDs were detected and quantified within 17 min without endogenous interferences. The correlation coefficient (R(2)) was >0.995 for all AEDs with accuracy ranging from 90 to 113% and precision <13% for all analytes. The recovery ranged from 70 to 98%. No carryover was observed in a blank control injected after the highest standard and the matrix effect was acceptable and ranged from 90 to 120%. The method has been successfully verified using authentic case samples that had previously been quantified using different methods.

Concentrations of basic drugs in postmortem blood require careful evaluation

Concentrations of basic drugs in postmortem blood require careful evaluation

Postmortem Drug Redistribution

Postmortem drug concentrations in blood may not always reflect antemortem drug concentrations in blood due to the movement of the drugs after death. The phenomenon is referred to as Postmortem Redistribution (PMR). Mechanisms involved in postmortem redistribution are both complicated and poorly understood. However, postmortem drug concentrations in blood do follow some generally accepted trends that aid with interpretation; the characteristics of the drug itself can be used to indicate if a drug is subject to PMR. Large changes in blood drug concentrations are predicted for basic, lipophilic drugs with a high volume of distribution (>3L/kg). When PMR occurs, blood specimens drawn from the central body cavity and heart generally will have higher drug concentrations postmortem than specimens drawn from peripheral areas, most commonly the femoral vein. The diffusion of drugs from organ tissue into the blood may explain the observed phenomenon [1]. To compensate for PMR, postmortem blood specimens are recommended to be collected from at least two areas of the body at autopsy; a peripheral area and a central area (often the heart), so that a comparison can be made. While antemortem blood specimens are especially helpful in interpreting postmortem blood drug concentrations, relevant specimens are only very rarely available. In a set of case studies of six drugs, drug concentrations in postmortem femoral blood specimens always exceeded the antemortem concentrations in five cases, suggesting that even peripheral blood may still exhibit some redistribution [2]. The study did not, however, report the postmortem interval been death and autopsy. It appeared that a partial answer to the difficulties associated with interpretation of postmortem drug concentrations was provided by two papers published in the 1990s. The first provided detailed information about blood drug concentrations attained from different sites for over fifty drugs [3]. The second provided a tabular list of the drug concentrations from both cardiac and peripheral blood samples expressed as a ratio of cardiac to peripheral blood (C/P) for over one hundred drugs [4]. The C/P ratio became the accepted benchmark with the accepted guideline that “high ratios” were associated with “potential for redistribution” [4]. This guideline was repeated in a review published a few years later that republished the C/P ratios for many of the drugs included in the Dalpe-Scott and coworker’s paper

Simultaneous screening and quantification of 25 opioid drugs in post-mortem blood and urine by liquid chromatography–tandem mass spectrometry

A method for simultaneous screening and quantification was developed for the fentanyls alfentanil, fentanyl, p-fluorofentanyl, cis-3-methylfentanyl, trans-3-methylfentanyl, alpha-methylfentanyl, norfentanyl, remifentanil, sufentanil, and the other opioid drugs 6-acetylmorphine, buprenorphine, codeine, dextropropoxyphene, ethylmorphine, heroin, methadone, morphine, naloxone, naltrexone, norbuprenorphine, normethadone, oxycodone, pentazocine, pethidine, and tramadol in post-mortem blood and urine samples by LC–MS/MS. Samples were extracted with butyl acetate at pH 7. The drugs were separated by LC on a Genesis C 18 reversed-phase column, with a gradient consisting of acetonitrile and ammonium acetate at pH 3.2. The mass spectrometric analysis was performed with a quadrupole-linear ion-trap mass spectrometer equipped with a turbo ion spray interface in positive mode using multiple reaction monitoring (MRM). Quantification was performed based on five isotope-labelled internal standards. Validation included assessment of linearity, limit of quantification, inaccuracy, precision, and matrix effects. The limits of quantification were adequate for screening and quantification of opioid drugs at low therapeutic or abuse concentration levels, with inaccuracy less than 23% and precision better than 24% both in blood and urine samples. When this method was applied to autopsy cases, its results were in agreement with those of reference methods.

Comparison of extraction efficiencies and LC–MS–MS matrix effects using LLE and SPE methods for 19 antipsychotics in human blood

Antipsychotic drugs are frequently associated with sudden death investigations. Detection of these drugs is necessary to establish their use and possible contribution to the death. LC-MS(MS) methods are common; however accurate and precise quantification is assured by using validated methods. This study compared extraction efficiency and matrix effects using common liquid-liquid and solid-phase extraction procedures in both ante-mortem and post-mortem specimen using LC-MS-MS. Extraction efficiencies and matrix effects were determined in five different blank blood specimens of each blood type. The samples were extracted using a number of different liquid-liquid extraction methods and compared with a standard mixed-mode solid-phase extraction method. Matrix effects were determined using a post-extraction addition approach-the blank blood specimens were extracted as described above and the extracts were reconstituted in mobile phase containing a known amount of analytes. The extraction comparison of ante-mortem and post-mortem blood showed considerable differences, in particular the extraction efficiency was quite different between ante-mortem and post-mortem blood. Quantitative methods used for determination of antipsychotic drugs in post-mortem blood should establish that there are no differences in extraction efficiency and matrix effects, particularly if using ante-mortem blood as calibrator.

Postmortem Kanda LC-MS MS ile Yasadışı Madde Taraması 62 Postmortem Adli Olguda Uygulanması

Biyolojik örneklerdeki yasadışı madde taraması adli olaylarda büyük bir öneme sahiptir. Kan veya plazma, madde derişim-leri ile bu maddelerin farmakolojik etkileri arasında iyi bir korelasyonun bulunması nedeniyle genellikle tercih edilen materyallerdir. Yasadışı madde analizinde, birçok laboratuar immunoassay yöntemleri ile tarama ve Gaz Kromatografi-Kütle Spektrometresi (GC-MS) ile doğrulama şeklinde bir uygulama yapmaktadır. Bununla birlikte, sıvı kromatografi tekniklerinin gelişmesiyle birlikte Sıvı Kromatografisi-Kütle Spektrometresi (LC-MS) ve tandem LC-MS (LC-MS/MS) birleştirilmiş tekniklerinde özellikle polar ve ısıya dayanıksız olan maddelerin nitel ve nicel analiz amaçlı olarak kullanımı zamanla artmaktadır. Bu çalışmada, LC-ESI (Electrospray İonisation)-MS/MS de morfin, (±)-amfetamin, (+)-metamfetamin, kokain, benzolekgonin, kokaetilen ve (-)-ll-nor-9-karboksi-t9-THC maddeleri taranmış ve tayin edilmiştir. Sonuç olarak, postmortem kanda uygulanabilecek, türevlendirme işlemine gerek duymayan, duyarlı ve seçimli olarak, çok düşük düzeylerdeki maddelerin doğru ve kesin olarak saptanmasını sağlayacak, LC-MS/MS yöntemi geliştirilmiş ve 62 postmortem adli olguya başarıyla uygulanmıştır.Anahtar kelimeler: Yasadışı madde, tarama, LC/MS/MS, postmortem kan

Postmortem Redistribution of the Enantiomers of Citalopram and Its Metabolites: An Experimental Study in Rats

A rat model was used to study if postmortem redistribution of the S- and R-enantiomers of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) occurs after three different subcutaneous dosing procedures with racemic CIT. Two groups underwent chronic administration (20 mg/kg daily) using osmotic pumps. After 10 days, 1 of these groups received an acute-on-chronic drug challenge with a single injection of 100 mg/kg. The third group received the single 100 mg/kg dose only. Heart blood and brain samples were collected antemortem and 1, 3, or 24 h postmortem for enantioselective HPLC analysis. Increased postmortem blood drug and metabolite concentrations compared with corresponding antemortem concentrations were observed in all groups (p < 0.05 to p < 0.001). At 24 h after death, the ratios between postmortem and antemortem blood concentrations were around 3-4 for CIT as well as for the metabolites. In the brain, no major differences between antemortem and postmortem drug and metabolite concentrations were observed. The enantiomeric (S/R) concentrations ratios of CIT and metabolites in blood and brain were of similar magnitude before and after death. No differences between antemortem and postmortem parent drug-to-metabolite (P/M) ratios for CIT/DCIT in blood were observed. Finally, this animal model demonstrates that the S- and R-enantiomers of CIT and its metabolites were redistributed to the same extent postmortem.

Amphetamines: an update on forensic issues.

Methamphetamine is currently enjoying a resurgence of popularity as a recreational drug. It presents a number of challenges to the forensic toxicologist both analytically and interpretively, and these latter interpretive issues are considered here. This review also discusses the current popular syntheses which account for the widespread domestic synthesis of the drug; the demographics of methamphetamine use in the United States as assessed from the Drug Abuse Warning Network (DAWN) data; developments in research of the neurotransporter pharmacology of the drug and its implications for interpretive forensic toxicology; the psychomotor effects of the drug and its potential for cognitive and functional impairment; interpretive issues related to postmortem blood drug concentrations and how these are impacted by evidence for incomplete distribution and the potential for postmortem redistribution; and, finally, concerns caused by designer methamphetamine analogues. All data indicate that methamphetamine and its analogues will present significant interpretive challenges to forensic toxicologists as the popularity of the drug continues to grow.

Criteria for judging whether postmortem blood drug concentrations can be used for toxicologic evaluation

Postmortem blood drug concentrations tend to be regional-dependent. The aim of this study was to establish preliminary criteria, based on analytical findings of drugs in body fluids, for objectively judging whether drug concentrations determined in postmortem blood are usable for toxicologic evaluation. The study involved 11 autopsy cases in which no obvious putrefaction was observed. Twelve drugs were assayed; the cumulative frequency of detection was 16. The drug concentrations in cerebrospinal fluid and pericardial fluid were averaged, and the ratio between this average concentration and the concentration in femoral venous blood was determined. The mean ratio was close to 1, with a small standard deviation (0.94 ± 0.20). From these results, the following criteria were drawn: 1) when the ratio of average cerebrospinal fluid/pericardial fluid drug concentration to blood drug concentration is within a range of 0.6–1.4, the postmortem blood drug concentration is usable for toxicologic evaluation; and 2) when the ratio is outside this range, the average cerebrospinal fluid/pericardial fluid concentration should be used as an alternative to drug concentration is postmortem blood.

Estimating antemortem drug concentrations from postmortem blood samples: the influence of postmortem redistribution

Aims—To compare blood drug concentrations during life with postmortem drug concentrations measured from a peripheral site and a central site. Methods—Coroner's cases from October 1990 to July 1997 were reviewed....

Screening postmortem blood and tissues for nine classes [correction of cases] of drugs of abuse using automated microplate immunoassay.

A commercially available enzyme-linked immunosorbant assay (ELISA) was evaluated as a screening procedure for the detection of nine classes of abused drugs in postmortem blood and tissue specimens. Specifically, postmortem blood, fluid and/or tissue homogenates were screened for amphetamine (AMP), methamphetamine (MET), barbiturates (BARB), benzodiazepines (BZD), cannabinoids (CNB), cocaine (benzoylecgonine; BE), morphine-specific (MOR), opiates (class; OPI), phencyclidine (PCP) and lysergic acid diethylamide (LSD) by ELISA and by coated tube radioimmunoassay (CTR) (BARB, BE, OPI, PCP, LSD) or double-antibody radioimmunoassay (DAR) (AMP/METH, BZD, CNB). Specimens that screened 'positive' by any method were confirmed and quantitated by gas chromatography/mass spectrometry (GC/MS). The only assay that appeared to perform less optimally than RIA was the MOR assay (five false negatives). However, this assay is very specific for free morphine while the GC/MS confirmation method provided a total morphine value. The OPI assay was more sensitive, producing fewer false negatives, and is recommended for broad class opiate screening. EIA is an adequate alternative to RIA for screening postmortem specimens, including blood and tissue, for nine major classes of drugs.