Research Progress on Biological Matrix Reference Materials in Forensic Toxicology / 法医学杂志

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.

Analysis of the Distribution of Total Phosphine and the Characteristics of Phosphine Poisoning in 29 Victims / 法医学杂志

OBJECTIVES@#To study the distribution of total phosphine in phosphine poisoning victims and summarize the characteristics of phosphine poisoning cases.@*METHODS@#The phosphine and its metabolites in the biological samples of 29 victims in 16 phosphine poisoning cases were qualified and quantified by headspace gas chromatography-mass spectrometry.@*RESULTS@#Five victims among 29 were poisoned by ingestion of aluminium phosphide and 24 by inhalation of phosphine gas. Phosphine metabolites were detected in the biological samples of 23 victims, and the concentrations of total phosphine in blood ranged 0.5-34.0 μg/mL. The total concentration of phosphine in liver tissue was up to 71.0 μg/g. Phosphine was not detected in the blood of the other six survived victims, which may be related to the small amount of phosphine exposure and the delay in blood sampling.@*CONCLUSIONS@#The total concentration of phosphine in blood and tissues caused by aluminum phosphine ingestion is higher than that caused by phosphine gas inhalation. The death cases of phosphine inhalation are characterized by long exposure time, repeated exposures and age susceptibility.

Benefits and risks of prolonged dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with stable coronary artery disease and diabetes / 中华心血管病杂志

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.

Identification of Methamphetamine Abuse and Selegiline Use: Chiral Analysis of Methamphetamine and Amphetamine in Urine / 法医学杂志

Objective To study the content variation of selegiline and its metabolites in urine, and based on actual cases, to explore the feasibility for the identification of methamphetamine abuse and selegiline use by chiral analysis. Methods The urine samples were tested by chiral separation and LC-MS/MS method using CHIROBIOTICTM V2 chiral liquid chromatography column. The chiral analysis of metham-phetamine and amphetamine were performed on the urine samples from volunteers of selegiline use and drug addicts whom suspected taking selegiline. Results After 5 mg oral administration, the positive test time of selegiline in urine was less than 7 h. The mass concentrations of R(-)-methamphetamine and R(-)-amphetamine in urine peaked at 7 h which were 0.86μg/mL and 0.18μg/mL and couldn't be de-tected after 80 h and 168 h, respectively. The sources of methamphetamine and amphetamine in the urine from the drug addicts whom suspected taking selegiline were analysed successfully by present method. Conclusion The chiral analysis of methamphetamine and amphetamine, and the determination of selegi-line's metabolites can be used to distinguish methamphetamine abuse from selegiline use.

Chlorpyrifos Determined in Human Blood by UPLC-MS/MS and Its Application in Poisoning Cases / 法医学杂志

OBJECTIVE@#To determine the chlorpyrifos in human blood by liquid chromatography-tandem mass spectrometry and to validate its application in poisoning cases.@*METHODS@#The samples were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Capcell Pack C18 MGII column (250 mm x 2.0 mm, 5 μm) using an isocratic elution of solvent A (0.1% formic acid-water with 2 mmol/L ammonium acetate) and solvent B (methanol with 2 mmol/L ammonium acetate) at 5:95 V:V).@*RESULTS@#The linear ranged from 5 to 500 ng/mL (r = 0.998 7). The limit of detection (LOD) and the lower limit of quantification (LLOQ) were 2 ng/mL and 4 ng/mL, respectively. For this method, the precision and accuracy of intra-day and inter-day were < 10% and 97.44%-101.10%, respectively. The results in stability test of long-term frozen were satisfied. The matrix effect, recovery and process efficiency were 64.97%-86.81%, 76.70%-85.52%, and 55.57%-66.58%, respectively.@*CONCLUSION@#This method can provide a rapid approach to chlorpyrifos extraction and determination in toxicological analysis of forensic and clinical treatment.

Chlorpyrifos Determined in Human Blood by UPLC-MS/MS and Its Application in Poisoning Cases / 法医学杂志

Objective To determine the chlorpyrifos in human blood by liquid chromatography-tandemmass spectrometry and to validate its application in poisoning cases. Methods The samples were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Capcell Pack C18 mG II column (250 mm×2.0 mm, 5μm) using an isocratic elution of solvent A (0.1% formic acid-water with 2 mmol/L ammoniumacetate) and solvent B (methanol with 2 mmol/L ammoniumacetate) at 5∶95 (V∶V).Results The linearranged from5 to 500ng/mL (r=0.9987).Thelimitofdetection (LOD) and the lower limit of quantification (LLOQ ) were 2 ng/mL and 4 ng/mL , respectively. For this method, the precision and accuracy of intra-day and inter-day were <10% and 97.44%-101.10%, respectively. The re-sults in stability test of long-termfrozen were satisfied. The matrix effect, recovery and process efficien-cy were 64.97%-86.81%, 76.70%-85.52%, and 55.57%-66.58%, respectively. Conclusion This method can provide a rapid approach to chlorpyrifos extraction and determination in toxicological analysis of forensic and clinical treatment.

Effect of 2-(carboxyphenyl) retinamide and genistein on the formation of early lesions in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

Aberrant crypt foci (ACF) are recognized as preneoplastic lesions for colon cancer, and ACF in rodents are widely used as an intermediate biomarker to predict tumorigenicity in the colon. However, a lack of correlations between the formation of ACF and the development of colonic tumors has been reported in several studies. For example, 2-(carboxyphenyl) retinamide (2-CPR) and genistein were reported to inhibit the carcinogen-induced formation of ACF, whereas both of them were later found to enhance colon tumorigenesis in rats treated with azoxymethane (AOM). Recently, we have identified b-catenin-accumulated crypts (BCAC) in the colon of rats shortly after administration of AOM, and provided evidence that these are independent early lesions of classical ACF, and BCAC might be direct precursors for colon cancers. In the present study, we performed a comparative analysis of the modifying effects of 2-CPR and genistein on 1,2-dimethylhydrazine (DMH)-induced BCAC and ACF in male F344 rats. Dietary administration of 2-CPR (315 ppm) significantly reduced the total number, multiplicity and size of ACF in DMH-exposed colonic mucosa, while genistein (250 ppm) had no significant effects on DMH-induced ACF formation. In contrast, both of 2-CPR and genistein significantly enhanced the multiplicity and size of DMH-induced BCAC when compared with DMH alone group. In addition, both 2-CPR and genistein significantly increased the proliferating cell nuclear antigen (PCNA) index preferentially in BCAC. Together with previous findings that 2-CPR and genistein are tumor promoters in the colon, our results support the concept that BCAC are precursors of colon tumors and suggest that these lesions are more reliable short-term biomarkers for colon carcinogenesis in rodents than ACF.