Sakamoto T, Endo M, Nagasaki A, Nakamura A, Watanabe S, Tanaka A, Nakahara Y
Laboratory of Drug Analysis, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Pharmazie. 1998 May;53(5):310-4.
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).
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。