Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms
Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms
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DOI：
10.1007/s11419-013-0206-5
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发表时间：
2015-01-01
影响因子：
2.2
通讯作者：
Suzuki, Osamu
中科院分区：
文献类型：
--
作者：
Hasegawa, Koutaro;Wurita, Amin;Suzuki, Osamu
在之前的一项研究中，我们发现非职业健康人的血液中存在相当数量的乙二醇（EG）、丙二醇（PG）和二甘醇（DEG）。在本研究中，我们用相同的同位素稀释气相色谱-质谱法测定了健康受试者尿液中的三种乙二醇，发现其浓度远高于血液中的浓度。随机抽取23名受试者的尿样中EG、PG和DEG的浓度（平均+/-标准差）分别为604 +/- A 360、5450 +/- A 9290和59.0 +/- A 49.3 ng/ml。这些数值分别是全血样本的9.44倍、30.1倍和5.31倍。在非职业健康人的尿液样本中发现的三种乙二醇的浓度要高得多，这表明这三种乙二醇一旦进入人体，就会迅速排出到尿液中。据我们所知，这是首次证明在健康受试者的尿液中存在相对高浓度的EG、PG和DEG。我们遇到了一个尸检病例，死因被判定为多种药物中毒，包括AB-CHMINACA、5-氟- amb和苯苯苯胺。死者是一名30岁男子。死后至尸检间隔估计为3.5天。收集股静脉血、右心血、左心血、尿液及包括脂肪组织在内的8种实体组织，冷冻以待分析。采用改进的QuEChERS法提取三种药物及内标品苯环利定和5-fluoro-AB-PINACA，然后采用液相色谱-串联质谱法分析。由于本研究涉及各种人体矩阵，我们采用标准加法法来克服矩阵效应。仅在脂肪组织中实现了所有三种化合物的定量，而在所有其他样品中，5-氟- amb的水平低于定量下限（约1 ng/g或ml）。AB-CHMINACA定量适用于所有实体组织，但不适用于所有体液标本。苯苯苯胺在所有标本中浓度均较高；它在脂肪组织中最高（11,100 +/- 1,120 ng/g），在其他固体组织标本中低一个数量级，在体液样本中低两个数量级。结果表明，脂肪组织是检测AB-CHMINACA、5-fluoro-AMB、苯苯苯胺等亲脂性药物的最佳样本。在这个中毒案例中，苯苯胺似乎在死亡原因中起了主要作用，因为在所有测试的标本中，苯苯胺的浓度远远高于合成大麻素的浓度。据我们所知，这是第一次在致命中毒案例的实际尸检标本中发现AB-CHMINACA、5-氟- amb和苯苯胺的报告。
In a previous study, we found that appreciable amounts of ethylene glycol (EG), propylene glycol (PG), and diethylene glycol (DEG) were present in the blood of nonoccupational healthy humans. In this study, we measured the three glycols in the urine of healthy subjects by the same isotope dilution gas chromatography-mass spectrometry method, and found the concentrations to be much higher than those in blood. The concentrations of EG, PG, and DEG in urine samples (mean +/- A standard deviation) obtained from 23 subjects at random were 604 +/- A 360, 5,450 +/- A 9,290, and 59.0 +/- A 49.3 ng/ml, respectively. These values were 9.44, 30.1, and 5.31 times higher than those in whole blood samples, respectively. The much higher concentrations of the three glycols found in urine samples of nonoccupational healthy humans suggest that the three glycols, once incorporated into the human body, are rapidly excreted into urine. To our knowledge, this is the first demonstration of the presence of relatively high concentrations of EG, PG, and DEG in urine of healthy human subjects.We encountered an autopsy case in which the cause of death was judged as poisoning by multiple drugs, including AB-CHMINACA, 5-fluoro-AMB, and diphenidine. The deceased was a 30-year-old man. The postmortem interval to autopsy was estimated to be 3.5 days. Femoral vein blood, right heart blood, left heart blood, urine, and eight solid tissues including adipose tissue were collected and frozen until analysis. Extraction of the three drugs, and internal standards phencyclidine and 5-fluoro-AB-PINACA was performed by a modified QuEChERS method, followed by analysis by liquid chromatography-tandem mass spectrometry. Because this study dealt with various kinds of human matrices, we used the standard addition method to overcome the matrix effects. Quantitation of all three compounds was only achieved for the adipose tissue, whereas the levels of 5-fluoro-AMB were below the lower limit of quantitation (about 1 ng/g or ml) in all other samples. AB-CHMINACA was quantitated for all solid tissues, but not for all body fluid specimens. Diphenidine showed high concentrations in all specimens; it was highest in the adipose tissue (11,100 +/- A 1,120 ng/g), an order of magnitude lower in other solid tissue specimens, and two orders of magnitude lower in body fluid samples. The results suggest that adipose tissue is the best specimen for detection of lipophilic drugs, such as AB-CHMINACA, 5-fluoro-AMB, and diphenidine, in their unchanged forms. In this poisoning case, diphenidine appeared to have played the major role in the cause of death, because the concentrations of diphenidine were much higher than those of the synthetic cannabinoids in all specimens tested. To our knowledge, this is the first report to document the presence of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in actual postmortem specimens in a fatal poisoning case.