1.The postmortem distribution of bromadiolone and its metabolite-benzylideneacetone in poisoned dogs
Danpin ZHAO ; Zeguo YANG ; Zhiwen WEI ; Shanlin FU ; Liang LIU ; Keming YUN
Chinese Journal of Forensic Medicine 2017;32(3):294-297
Objective To study the postmortem distribution of Bromadiolone and its metabolite-Benzylideneacetone in dogs and provide an experimental evidence for the sampling of Bromadiolone poisoning cases. Methods The dogs were given 2LD50 and 4LD50 Bromadiolone by intragastric administration. Anatomy was conducted immediately after death and samples of body fluids and viscera (heart blood; peripheral blood, bile, urine, heart, liver, spleen, lung, kidney, brain, urinary bladder, left leg muscle, stomach, stomach contents, pancreas) were collected and detected after the dogs poisoning death. The Bromadiolon and its metabolite-Benzylideneacetone contents in samples were analyzed by GC/MS. Results Hemorrhagic symptoms came out at 3d after Bromadiolone delivery and deaths occurred at (178.40±20.94)h after intoxication. The postmortem distribution of Bromadiolon and its metabolite-Benzylideneacetone in dogs was as following: 2LD50 Bromadiolon: bile>urine, liver, heart, kidney>heart blood, peripheral blood, spleen, lung and so on. Benzylideneacetone: the content in bile, urine, heart blood, peripheral blood, lung, stomach contents are higher. 4LD50 Bromadiolon: bile, urine>liver, peripheral blood>heart blood, stomach contents and others. Benzylideneacetone:contents in bile, urine and lung are higher. Conclusion The postmortem distribution of Bromadiolon and its metabolite-Benzylideneacetone in dogs is uneven, contents in bile, urine, liver, heart blood and peripheral blood are higher, whichare suggested for forensic toxicological analysis in Bromadiolon poisonig case.
2.Study on the pharmacokinetics of clozapine and its metabolites in human blood
Yefei PAN ; Zhiwen WEI ; Xiaohui TAN ; Yao LIU ; Fu SHANLIN ; Ande MA ; Kemeng YUN
Chinese Journal of Forensic Medicine 2017;32(3):240-244
Objective To study the pharmacokinetics and detection window of clozapine and its metabolites in human blood, so as to provide experimental basis for forensic cases of identification of clozapine poisoning. Methods 29 Taiyuan Han people's elbow venous blood was collected after given oral administration of 12.5mg clozapine at different time point, in which clozapine and its metabolites were extracted with solid phase extraction (SPE) and determined by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Using the 3p97 pharmacokinetic software, pharmacokinetic equation of clozapine in the blood were imitated from the C-T data, and pharmacokinetic parameters were calculated. Results The pharmacokinetics of clozapine met a two compartment open model with a first kinetics absorption. The Tmax of clozapine(CLP), demethylclozapine(DMCLP), N-oxidation-clozapine(NO-CLP) respectively were 2.96±1.32h, 8.65±3.00h, 9.31±26.38h; The Cmax of CLP, DMCLP, NO-CLP respectively were 34.68±9.32ng/mL, 11.16±4.15ng/mL, 9.62±13.88ng/mL;The t1/2 of CLP, DMCLP, NO-CLP respectively were 17.02±23.63h, 27.06±12.58h, 41.27±29.75h; The detection window of CLP, DMCLP, NO-CLP respectively were 81.72±26.19h, 93.21±29.40h and 19.93±14.62h. Conclusion The pharmacokinetics of clozapine in blood of Han people is consistent with two compartment open model with a first kinetics absorption. The pharmacokinetics model and parameters of clozapine can provide expirimental basis for forensic identification of clozapine poisoning cases.
3.Study on the stability of carbofuran and its metabolites in blood preserved at different conditions
Aiai FAN ; Yanan SHEN ; Feng ZHENG ; Zhiwen WEI ; Yao LIU ; Shanlin FU ; Keming YUN
Chinese Journal of Forensic Medicine 2017;32(6):578-582,587
Objective Study on the stability of carbofuran and its metabolite carbofuran phenol in blood preserved at different conditions,in order to provide a scientific evidence for forensic identification of carbofuran poisoning death. Methods The dogs were given intragastric administration with 4LD50(13.5mg/kg) of carbofuran, the blood were collected and divided into five equally groups preserved at 20℃(NC2.5mg/mL), 20℃(1%NaF), 20℃, 4℃ and -20℃, respectively. The concentrations of carbofuran and carbofuran phenol in above samples were detected by GC-MS/MS with MRM at 0d、5d、7d、15d、40d、83d and 150d. Results The concentration of carbofuran in preserved blood were found to be significant decrease at 7d(P < 0.05), then a steady decline. In each condition, the concentration of carbofuran phenol in preserved blood showed an increasing trend firstly, then a declined tendency. The concentration of carbofuran and carbofuran phenol descending fast in blood at 20 ℃ (NC) and 20 ℃ (1%NaF).Conclusion Carbofuran and carbofuran phenol in preserved specimens are found to be decomposed. The decomposition is quick at 20℃ and slow at -20℃. Citrate sodium and sodium fluoride are not suit for anticoagulation and antiputrefactiva. Biological specimens used for forensic identification of the carbofuran poisoning should be stored at refriferated or freezed, and be analyzed as soon as possible.
4.Simultaneous determination of somedon and its metabolites by GC–MS/MS
Yanan SHEN ; Juan JIA ; Feng ZHENG ; Aiai FAN ; Zhiwen WEI ; Yao LIU ; Shanlin FU ; Keming YUN
Chinese Journal of Forensic Medicine 2017;32(6):573-577,587
Objective To develop a method of support liquid-liquid extraction (SLE) and simultaneous determination of 4 components in somedon and its 8 metabolites by GC–MS/MS. Methods Somedon and its metabolites were extracted by SLE and determined by GC-MS/MS in MRM mode. The qualitative analysis was based on retention time and ratio of ions. The quantitative analysis was based on internal standard method and calibration curve. Results After SLE and determination of 4 components in somedon and its 8 metabolites, the extraction rate were 37.57%~95.87%, the linear range were 0.12μg/mL~16.00μg/mL, the correlation coefficient(r)were 0.989 6~0.999 7, LOD were 0.08ng/mL~14.48ng/mL, the accuracy were 79.63%~122.90%, the interday and intraday precision were 0.99%~7.43% and 2.19%~10.60% respectively. Conclusion Simultaneous determination of somedon and its metabolites by GC–MS/MS in biological samples, which was rapid, simple, accurate and was high precision and recovery, can be used for qualitative and quantitative analysis in forensic cases.