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服用药物泛普法宗后苯丙胺和甲基苯丙胺的代谢概况。

Metabolic profile of amphetamine and methamphetamine following administration of the drug famprofazone.

作者信息

Greenhill Brandy, Valtier Sandra, Cody John T

机构信息

Graduate Program in Clinical Laboratory Sciences, Department of Clinical Laboratory Sciences, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA

出版信息

J Anal Toxicol. 2003 Oct;27(7):479-84. doi: 10.1093/jat/27.7.479.

Abstract

There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the proportion was approximately 70% l-methamphetamine and this proportion increased over time. Amphetamine results showed l- and d-amphetamine were virtually the same in the early samples with the proportion of l-amphetamine increasing as time progressed. Forensic interpretation of drug testing results is a challenging critical part of forensic drug testing area because of the potential repercussions the results found may have on an individual's life. The finding of each enantiomers by itself differentiates famprofazone use from the most commonly abused form of methamphetamine and all medicinal methamphetamine available in the U.S., which is either d-methamphetamine (prescription medication) or l-methamphetamine (Vicks inhaler). Coupling this information with the concentrations of amphetamine and methamphetamine helps to determine the potential for use of this drug.

摘要

有几种药物会在体内导致甲基苯丙胺和/或苯丙胺的产生,随后这些物质会通过尿液排出。在解读苯丙胺类药物检测呈阳性的结果时,这些药物引发了明显的担忧。泛普法宗是一种存在于用于缓解疼痛的多成分药物(格沃丁)中的镇痛药。向无苯丙胺、甲基苯丙胺或泛普法宗使用史的健康志愿者口服两片格沃丁(每片含50毫克泛普法宗)。给药后,随意收集尿液样本长达6天,并测定pH值、比重和肌酐值。为了确定苯丙胺和甲基苯丙胺的定量排泄情况,样本采用液液萃取法提取,用七氟丁酸酐衍生化,然后通过气相色谱 - 质谱联用仪(GC - MS)进行分析。监测的苯丙胺离子为91、118、240,甲基苯丙胺离子为254、210、118。苯丙胺 - d(6)和甲基苯丙胺 - d(11)用作内标。苯丙胺的峰值浓度范围为148至2271纳克/毫升,甲基苯丙胺为615至7361纳克/毫升。两种化合物的浓度在给药后3至7小时达到峰值。苯丙胺和甲基苯丙胺分别在给药后121小时和143小时可被检测到(检测限 = 5纳克/毫升)。使用500纳克/毫升的截断值,所有受试者的个体尿液样本检测均呈阳性。一名受试者有14个样本高于截断值,最后一个阳性样本在给药后48小时以上被检测到。还采用液液萃取法、用N - 三氟乙酰 - l - 脯氨酰氯衍生化并通过GC - MS分析来确定甲基苯丙胺和苯丙胺对映体的情况。数据显示泛普法宗的代谢产物苯丙胺和甲基苯丙胺均为d - 和l - 对映体。从收集的第一个样本开始,l - 甲基苯丙胺的比例就超过了其d - 对映体。最初,该比例约为70%的l - 甲基苯丙胺,且这一比例随时间增加。苯丙胺的结果显示,早期样本中l - 和d - 苯丙胺几乎相同,随着时间推移l - 苯丙胺的比例增加。由于药物检测结果可能对个人生活产生潜在影响,因此对药物检测结果进行法医学解读是法医学药物检测领域具有挑战性的关键部分。每种对映体的发现本身就将泛普法宗的使用与美国最常见的滥用形式甲基苯丙胺以及所有药用甲基苯丙胺区分开来,美国的药用甲基苯丙胺要么是d - 甲基苯丙胺(处方药),要么是l - 甲基苯丙胺(维克斯吸入器)。将这些信息与苯丙胺和甲基苯丙胺的浓度相结合,有助于确定使用这种药物的可能性。

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