Biological matrix reference material is a reference material that combines the target material with the biological matrix. The biological matrix reference material has higher consistency with the authentic specimens in forensic toxicology, and its application has a positive effect on improving the accuracy of test results. This paper reviews the research on the matrix reference materials corresponding to three common biological test materials (blood, urine and hair). In order to provide reference for the development and application of biological matrix reference materials in forensic toxicology, this paper mainly introduces the research progress of preparation technology of biological matrix reference materials and some existing products and their parameters evaluation.
Forensic Toxicology/methods* ; Hair ; Body Fluids

Hanging is the most common method of suicide in Malaysia. However, hanging in combination with suicidal ligature strangulation is uncommon. The victim is a 31-year-old man, with no previous medical or psychiatric disorders. He accomplished self-strangulation using a shoelace and hanging himself with a High-Definition Multimedia Interface cable. Three loops of a shoelace ligature were present around the neck. A single knot was present on the front, and a double knot at the back of the neck. Internal examination of the neck revealed small bilateral hemorrhages of the sternocleidomastoid muscles. No laryngeal cartilage or hyoid bone fractures were observed. No other evidence of injury was noted other than moderate pulmonary edema. The post-mortem toxicology results were negative. The cause of death was ascertained as neck compression due to ligatures. Scene assessment and post-mortem findings concur with suicide. This report describes an unusual case of suicidal ligature strangulation, in combination with hanging using two different ligatures.
Adult ; Cause of Death ; Hemorrhage ; Humans ; Hyoid Bone ; Laryngeal Cartilages ; Ligation ; Malaysia ; Methods ; Multimedia ; Muscles ; Neck ; Pulmonary Edema ; Suicide ; Toxicology

Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.
Chromatography, High Pressure Liquid/methods* ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Humans ; Sex Offenses ; Tandem Mass Spectrometry/methods* ; Tiletamine/blood* ; Zolazepam/blood*

OBJECTIVES: To identify the new designer drugs which are totally unknown and not in the routine testing list by the technologies such as high-resolution mass spectrometry in drug facilitated sexual assault, in order to solve the problem in actual cases. METHODS: The milky fluid from an actual case was extracted and analyzed using LC-QE, ¹H-NMR and GC-MS, respectively. The accurate masses and cluster ions isotope patterns of unknown compound were obtained by LC-QE. The molecular formula was confirmed as C₁₆H₁₂C₂N₂O based on the protons number of ¹H-NMR. The isomers diclazepam and 4-chlorodiazepam were separated and detected with GC-MS. RESULTS: The new designer benzodiazepine as diclazepam in the milky fluid was identified. The results provided direct evidence for the investigation and qualitative analysis of such cases. CONCLUSIONS The combined application of various methods, including LC-QE, ¹H-NMR and GC-MS, can be used to detect unknown new psychoactive substances.
Benzodiazepines/chemistry* ; Benzodiazepinones ; Chromatography, Liquid/methods* ; Designer Drugs/chemistry* ; Female ; Gas Chromatography-Mass Spectrometry/methods* ; Humans ; Male ; Mass Spectrometry/methods* ; Sex Offenses ; Substance Abuse Detection/methods* ; Toxicology/methods*

The demand for rapid and broad clinical toxicology screens is on the rise. Recently, a new rapid toxicology screening test, the Triage TOX Drug Screen (Alere Inc., USA), which can simultaneously detect 11 drugs of abuse and therapeutic drugs with an instrument-read cartridge, was developed. In the present study, we evaluated the efficacy of this new on-site immunoassay using 105 urine specimens; the results were compared with those obtained by using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-TMS). Precision was evaluated according to the CLSI EP12-A2 for analyte concentrations near the cutoff, including C₅₀ and±30% of C₅₀, for each drug using standard materials. The C₅₀ specimens yielded 35–65% positive results and the ±30% concentration range of all evaluated drugs encompassed the C₅–C₉₅ interval. The overall percent agreement of the Triage TOX Drug Screen was 92.4–100% compared with UPLC-TMS; however, the Triage TOX Drug Screen results showed some discordant cases including acetaminophen, amphetamine, benzodiazepine, opiates, and tricyclic antidepressants. The overall performance of the Triage TOX Drug Screen assay was comparable to that of UPLC-TMS for screening of drug intoxication in hospitals. This assay could constitute a useful screening method for drugs of abuse and therapeutic drugs in urine.
Acetaminophen ; Amphetamine ; Antidepressive Agents, Tricyclic ; Benzodiazepines ; Chromatography, Liquid ; Immunoassay ; Mass Screening ; Methods ; Street Drugs* ; Tandem Mass Spectrometry ; Toxicology ; Triage*

OBJECTIVES: To infer the frequency of dosage and medication history investigate of the victims in drug facilitated cases by the segmental analysis of clonazepam in hair. METHODS: Freezing milling under liquid nitrogen environment combined with ultrasonic bath was used as sample pretreatment in this study, and liquid chromatography-tandem mass spectrometry was used for the segmental analysis of the hair samples collected from 6 victims in different cases. The concentrations of clonazepam and 7-aminoclonazepam were detected in each hair section. RESULTS: Clonazepam and its metabolite 7-aminoclonazepam were detected in parts of hair sections from the 6 victims. The occurrence time of drug peak concentration was consistent with the intake timing provided by victims. CONCLUSIONS Segmental analysis of hair can provide the information of frequency of dosage and intake timing, which shows an unique evidential value in drug facilitated crimes.
Adult ; Chromatography, Liquid ; Clonazepam/analysis* ; Crime ; Forensic Medicine/methods* ; Forensic Toxicology ; Hair/chemistry* ; Humans ; Mass Spectrometry ; Spectrometry, Mass, Electrospray Ionization ; Substance Abuse Detection/methods* ; Ultrasonics

Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced.
Research Design ; Risk Assessment ; Toxicology ; methods

Metabonomics is an important branch of system biology following the development of genomics, transcriptomics and proteomics. It can perform high-throughput detection and data processing with multiple parameters, potentially enabling the identification and quantification of all small metabolites in a biological system. It can be used to provide comprehensive information on the toxicity effects, toxicological mechanisms and biomarkers, sensitively finding the unusual metabolic changes caused by poison. This article mainly reviews application of metabonomics in toxicological studies of abused drugs, pesticides, poisonous plants and poisonous animals, and also illustrates the new direction of forensic toxicology research.
Animals ; Biomarkers ; Forensic Toxicology/methods* ; Humans ; Metabolomics/methods*

OBJECTIVE: The demand for rapid and broad clinical toxicology screening methods to identify drugs of abuse and medicinal drugs is increasing steadily. Liquid chromatography-tandem mass spectrometry (LC-TMS) is increasingly used to screen for drugs of abuse and to identify a wide range of drugs and metabolites in clinical samples. We revised a high-throughput and rapid ultra-performance (UP) LC-TMS method for simultaneous screening of 177 of the most prevalent medicinal drugs and drugs of abuse in urine and validated the quality of performance using system suitability mixture (SSM) and quality control (QC) materials. METHODS: We assessed the limits of detection (LOD) using high concentrations of the test substances. The method was applied to 473 urine samples obtained from patients intoxicated with drugs who visited the emergency center. RESULTS: The retention time, peak area, and total ion chromatogram of the SSM and QC materials were within the acceptance criteria of the pre-defined acceptance interval. The LODs were <62 ng/ml for 12 commonly encountered drugs. In total, 418 patients (88.4%) tested positive for one or more medicinal drugs or drugs of abuse. Twenty-eight drugs were detected over ten times; the most commonly detected were zolpidem, ephedrine, paracetamol, and chlorpheniramine. CONCLUSION: The UPLC-TMS method provided excellent performance for simultaneous screening of a large number of the drugs of abuse in urine samples. We conclude that this robust technique is useful for screening for a large number of drugs and for rapid screening of the most commonly encountered substances in emergency cases.
Acetaminophen ; Chlorpheniramine ; Chromatography, Liquid* ; Emergencies ; Ephedrine ; Humans ; Limit of Detection ; Mass Screening* ; Mass Spectrometry ; Methods ; Quality Control ; Street Drugs* ; Tandem Mass Spectrometry* ; Toxicology

OBJECTIVE: To establish an animal model in acute poisoned rat by deltamethrin and an analysis method for determination of deltamethrin by gas chromatography-electron capture detector (GC-ECD) and to study the distribution of deltamethrin in rats in order to provide the references for forensic medicine identification about such cases. METHODS: Rats were administered with deltamethrin of different doses(512 and 1,024 mg/kg) and killed 1.5 h later to be dissected rapidly for tissues (blood, hearts, livers, lungs, kidneys and brains etc.). Samples were dehydrated by anhydrous sodium sulfate and extracted with petroleum ether and acetone (V:V=4:1). The level of deltamethrin was determined by GC-ECD. RESULTS: There was a good separate between deltamethrin and endogenous impurities. The limit of quantification for deltamethrin in blood and liver were 0.1 microg/mL and 0.1 microg/g (S/N> or =10), respectively. The recovery rate of deltamethrin in blood was 91.55%-134.37% and both inter-day and intra-day precisions were less than 5.67%. The distribution of deltamethrin in poisoned rats with 512 mg/kg was as follow: lungs > livers > hearts > kidneys > blood > brains and with 1 024 mg/kg dose was lungs > blood > hearts > kidneys > brains > livers (P<0.05). CONCLUSION The GC-ECD method is sensitive for determination of deltamethrin. The distribution of deltamethrin in rats has a dose-dependent manner. The study suggests that samples of blood, hearts, livers, lungs, kidneys and brains are suitable for deltamethrin poisoned analysis.
Animals ; Chromatography, Gas/methods* ; Disease Models, Animal ; Forensic Toxicology/methods* ; Kidney/metabolism* ; Linear Models ; Liver/metabolism* ; Lung/metabolism* ; Male ; Nitriles/poisoning* ; Pyrethrins/poisoning* ; Rats ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Distribution