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大鼠毛根中苯环利定急性中毒的毛根分析及苯环利定代谢物行为评估。

Evaluation of hair root analysis for acute phencyclidine poisoning and behavior of phencyclidine metabolites in rat hair root.

作者信息

Sakamoto T, Endo M, Nagasaki A, Nakamura A, Watanabe S, Tanaka A, Nakahara Y

机构信息

Laboratory of Drug Analysis, Showa College of Pharmaceutical Sciences, Tokyo, Japan.

出版信息

Pharmazie. 1998 May;53(5):310-4.

PMID:9631500
Abstract

We evaluated the usefulness of hair root analysis to diagnose acute phencyclidine (PCP) poisoning. Male rats were i.p. administered acute poisonous doses (80, 100 and 120 mg/kg) of PCP hydrochloride and the hair roots were plucked out with hair nippers at certain times after administration. The hair root samples were extracted with methanol/HCl. After evaporation of the solvent, the residue was derivatized with N,O-bis(trimethylsilyl) acetamide and analyzed with GC/MS. PCP was detected at high concentrations (up to 181.7 ng/mg) from all samples. The peak concentrations at every dose were observed at 6 h. The concentrations of PCP in the rat hair roots increased dose-dependently in the range of the doses. 1-(1-Phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-phenyl-1(4'-hydroxypiperidino)-4-cyclohexanol (t-PCPdiol) were also detected from 5 and 15 min to 48 h after administration, respectively. It is concluded that hair root is a useful specimen for the diagnosis of acute PCP poisoning because PCP, PCHP and t-PCPdiol are detected very soon after administration and a large amount of them is retained in hair root for a long time. PCHP was found from the early stage in hair roots and its concentration was higher than that of t-PCPdiol for 6 h. However, the concentration of t-PCPdiol became higher than that of PCHP after 6 h. These phenomena could be explained by the time lag of production of the primary (PCHP) and the secondary metabolite (PCPdiol).

摘要

我们评估了发根分析在诊断急性苯环己哌啶(PCP)中毒方面的实用性。给雄性大鼠腹腔注射急性中毒剂量(80、100和120 mg/kg)的盐酸PCP,并在给药后的特定时间用拔毛钳拔出毛发根部。将毛发根部样品用甲醇/盐酸提取。溶剂蒸发后,残留物用N,O-双(三甲基硅基)乙酰胺衍生化,并用气相色谱/质谱联用仪进行分析。在所有样品中均检测到高浓度(高达181.7 ng/mg)的PCP。每个剂量下的峰值浓度在6小时时观察到。在该剂量范围内,大鼠毛发根部中PCP的浓度呈剂量依赖性增加。在给药后5分钟至48小时内,还分别检测到了1-(1-苯基环己基)-4-羟基哌啶(PCHP)和反式-1-苯基-1(4'-羟基哌啶基)-4-环己醇(t-PCP二醇)。得出结论,发根是诊断急性PCP中毒的有用标本,因为给药后很快就能检测到PCP、PCHP和t-PCP二醇,并且它们中的大量物质会在发根中长时间留存。在发根中早期就发现了PCHP,其浓度在6小时内高于t-PCP二醇。然而,6小时后t-PCP二醇的浓度变得高于PCHP。这些现象可以通过初级代谢产物(PCHP)和次级代谢产物(PCP二醇)产生的时间滞后来解释。

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