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伊博格滥用后通过液相色谱-串联质谱法测定生物体液和毛发中的伊波加因和去甲伊波加因 伊波加生物碱在一例溺水死亡案件中的分布情况

Determination of ibogaine and noribogaine in biological fluids and hair by LC-MS/MS after Tabernanthe iboga abuse Iboga alkaloids distribution in a drowning death case.

作者信息

Chèze Marjorie, Lenoan Aurélie, Deveaux Marc, Pépin Gilbert

机构信息

Laboratoire TOXLAB, 7 rue Jacques Cartier, F-75018 Paris, France.

出版信息

Forensic Sci Int. 2008 Mar 21;176(1):58-66. doi: 10.1016/j.forsciint.2007.08.013. Epub 2007 Nov 19.

DOI:10.1016/j.forsciint.2007.08.013
PMID:18024037
Abstract

Tabernanthe iboga belongs to the Apocynaceae family. In this study, we report the case of a 37-year-old black male working as a security agent in Paris and found dead naked on the beach in Gabon after consumption of iboga. Autopsy revealed a drowning fatality and a myocardial abnormality (myocardial bridging). Samples of blood, urine, bile, gastric content, liver, lungs, vitreous, spleen and hair were taken. Biological fluids were liquid-liquid extracted with saturated NH4Cl pH 9.5 and methylene chloride/isopropanol (95/5, v/v) in presence of clonazepam-d(4), used as internal standard. After decontamination with dichloromethane, hair was cut into small pieces then sonicated for 2h in saturated NH4Cl pH 9.5 before extraction by methylene chloride/isopropanol (95/5, v/v). After evaporation the residues were reconstituted in methanol/ACN/formate buffer pH 3, from which 10 microL were injected into an ODB Uptisphere C(18) column (150 mm x 2.1mm, 5 microm) and eluted with a gradient of acetonitrile and formate buffer delivered at a flow rate of 200 microL/min. A Quantum Ultra triple-quadrupole mass spectrometer was used for analyses. Ionization was achieved using electrospray in the positive ionization mode (ESI). For each compound, detection was related to three daughter ions (ibogaine: m/z 311.4-->122.1, 174.1 and 188.1; noribogaine: m/z 297.4-->122.1, 159.1 and 160.1; clonazepam-d(4): m/z 319.9-->218.1, 245.1 and 274.1). Ibogaine and noribogaine were detected in all autopsy samples. Hair segmentation was not possible as hair was very short and frizzy. Concentrations of 1.2 and 2.5 ng/mg, respectively were detected. Neither other licit or illicit drugs nor alcohol were found. The presence of ibogaine and noribogaine in all autopsy samples was consistent with the recent absorption of Tabernanthe iboga, which was assumed to be responsible of the drowning fatality. The history of exposure, regarding hair analysis, is discussed. LC-MS/MS appears to be the best method for analyzing complex and poorly volatile alkaloids in autopsy samples and particularly in hair, due to the presence of a nitrogen ring and the relatively low concentrations to be measured.

摘要

伊博格碱(Tabernanthe iboga)属于夹竹桃科。在本研究中,我们报告了一例37岁黑人男性的案例,该男子在巴黎担任保安,在食用伊博格碱后被发现赤身裸体死于加蓬的海滩上。尸检显示为溺水死亡以及心肌异常(心肌桥)。采集了血液、尿液、胆汁、胃内容物、肝脏、肺、玻璃体、脾脏和毛发样本。生物体液用饱和氯化铵(pH 9.5)和二氯甲烷/异丙醇(95/5,v/v)进行液-液萃取,内标为氯硝西泮-d4。毛发用二氯甲烷净化后,切成小块,然后在饱和氯化铵(pH 9.5)中超声处理2小时,再用二氯甲烷/异丙醇(95/5,v/v)萃取。蒸发后,残渣用甲醇/乙腈/甲酸缓冲液(pH 3)复溶,取10微升注入ODB Uptisphere C18柱(150毫米×2.1毫米,5微米),以乙腈和甲酸缓冲液的梯度洗脱,流速为200微升/分钟。使用Quantum Ultra三重四极杆质谱仪进行分析。采用电喷雾在正离子模式(ESI)下实现电离。对于每种化合物,检测与三个子离子相关(伊博格因:m/z 311.4→122.1、174.1和188.1;去甲伊博格因:m/z 297.4→122.1、159.1和160.1;氯硝西泮-d4:m/z 319.9→218.1、245.1和274.1)。在所有尸检样本中均检测到伊博格因和去甲伊博格因。由于毛发非常短且卷曲,无法进行毛发分段。分别检测到浓度为1.2和2.5纳克/毫克。未发现其他合法或非法药物及酒精。所有尸检样本中伊博格因和去甲伊博格因的存在与近期摄入伊博格碱一致,推测这是导致溺水死亡的原因。讨论了关于毛发分析的暴露史。液相色谱-串联质谱法似乎是分析尸检样本尤其是毛发中复杂且挥发性差的生物碱的最佳方法,这是由于存在氮环以及要测量的浓度相对较低。

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