Gole D J, Pirat J L, Kamenka J M, Domino E F
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Drug Metab Dispos. 1988 May-Jun;16(3):386-91.
A new sensitive and specific GC-MS assay was developed to quantify monohydroxy metabolites of phencyclidine (PCP) from biological samples. The method is based on the two-step extraction of PCP and related basic metabolites in an organic solvent followed by a capillary column GC separation and mass selective detection of the extract derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide. The detection limit of the method is about 5 pmol with a linear standard curve to 3 nmol/injection. The assay was used for the quantification of monohydroxy metabolites in the urine of PCP-dosed mice and rats. A new compound (specifically selected for this study), 1-phenyl-1-(1-[3-hydroxymethyl]piperidinyl)cyclohexane, was used as the internal standard. The internal standard was selected to closely mimic the chemical characteristics of potential alicyclic hydroxy metabolites of PCP. The in vitro biotransformation of PCP by mouse and rat liver microsomes also was studied. The presence of a recently identified metabolite, 3-phenyl-3-(1-piperidinyl)-trans-cyclohexanol was confirmed. A new metabolite, 1-phenyl-1-(1-piperidinyl-3-ol)cyclohexane, was identified and quantified in the urine and liver microsomal preparations.
开发了一种新的灵敏且特异的气相色谱 - 质谱（GC-MS）分析方法，用于定量生物样品中苯环己哌啶（PCP）的单羟基代谢物。该方法基于在有机溶剂中对PCP及相关碱性代谢物进行两步萃取，随后通过毛细管柱气相色谱分离，并对用N,O-双（三甲基硅基）三氟乙酰胺衍生化的萃取物进行质量选择性检测。该方法的检测限约为5皮摩尔，线性标准曲线可达3纳摩尔/进样。该分析方法用于定量给予PCP的小鼠和大鼠尿液中的单羟基代谢物。一种新化合物（专门为本研究选择），1-苯基-1-(1-[3-羟甲基]哌啶基)环己烷，用作内标。选择该内标是为了紧密模拟PCP潜在脂环族羟基代谢物的化学特性。还研究了小鼠和大鼠肝微粒体对PCP的体外生物转化。确认了最近鉴定出的一种代谢物3-苯基-3-(1-哌啶基)-反式-环己醇的存在。在尿液和肝微粒体制剂中鉴定并定量了一种新的代谢物1-苯基-1-(1-哌啶基-3-醇)环己烷。
