a Department of Anatomical, Histological, Forensic and Orthopaedic Sciences , Sapienza University of Rome , Rome , Italy.
b Department of Clinical Pharmacology , University of Linköping , Linköping , Sweden.
Clin Toxicol (Phila). 2019 Mar;57(3):149-163. doi: 10.1080/15563650.2018.1519194. Epub 2018 Oct 11.
γ-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths.
The aim of this review is to assist clinical and forensic practitioners with the interpretation of γ-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons.
The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords γ-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine γ-hydroxybutyric acid in blood and other biological specimens make use of gas- or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of γ-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cut-offs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All biological fluids and tissue containing water are suitable for the analysis of GHB. Examples of alternative specimens discussed in this review are CSF, saliva, hair strands, breast milk, DBS, VH, and brain tissue.
Body fluids for the analysis of GHB must be obtained as quickly as possible after a poisoned patient is admitted to hospital or after a person is arrested for a drug-related crime to enhance chances of detecting the drug. The sampling of urine lengthens the window of detection by 3-4 h compared with blood samples, but with longer delays between last intake of GHB and obtaining specimens, hair strands, and/or nails might be the only option. In postmortem toxicology, the concentrations of drugs tend to be more stable in bladder urine, VH, and CSF compared with blood, because these sampling sites are protected from the spread of bacteria from the gut. Accordingly, the relationship between blood and urine concentrations of GHB furnishes useful information when drug intoxication deaths are investigated.
γ-羟基丁酸是一种内源性物质、治疗剂和滥用的娱乐性药物。这种精神活性物质是中枢神经系统的抑制剂，在临床和法医实践中很常见，包括受影响的司机、中毒患者和与药物相关的中毒死亡。
本综述的目的是帮助临床和法医从业者解释血液、尿液和来自活人和死者的替代生物样本中的 γ-羟基丁酸浓度。
用于准备本综述的信息来源是 PubMed、Scopus 和 Web-of-Science。使用 γ-羟基丁酸（GHB）、血液、尿液、替代标本、非传统生物基质、唾液、口腔液、汗液、头发、玻璃体（VH）、脑、脑脊液（CSF）、干血斑（DBS）、母乳和各种组合等关键词搜索这些数据库。筛选出 4228 篇参考文献以排除重复项，剩下 1980 篇文章供进一步考虑。仔细评估这些出版物，同时考虑到综述的主要目的，并认为 143 篇科学论文是相关的。分析方法：用于确定血液和其他生物样本中 γ-羟基丁酸的分析方法利用气相或液相色谱法与质谱法相结合。这些联用技术准确、精确、专门用于其预期目的，血液和其他样本的定量下限为 0.5mg/L 或更低。人体药代动力学：GHB 从肠道迅速吸收并分布到全身的水相。只有一小部分剂量（1-2%）以未改变的形式在尿液中排出。γ-羟基丁酸的血浆消除半衰期很短，仅约 0.5-0.9 小时，这需要及时采集血液和其他生物样本进行临床和法医分析。血液中 GHB 的内源性浓度：GHB 既是内源性代谢物又是滥用药物，这使得对实验室分析结果的解释变得复杂。此外，血液和其他标本中的 GHB 浓度在采样后往往会增加，尤其是在尸检案例中。这需要使用实际的“截止”浓度来避免报告假阳性结果。这些截止值因不同的生物标本类型而有所不同。临床和法医实践中的 GHB 浓度：作为一种娱乐性药物，GHB 主要由平均年龄为 27.1 岁的年轻男性（94%）使用。从被捕司机血液中检测到的 GHB 的平均（中位数）和范围浓度分别为 90mg/L（82mg/L）和 8-600mg/L。从活着和死去的人身上采集的血液浓度分布重叠，尽管中毒死亡者的平均（中位数）和范围浓度更高；分别为 640mg/L（280mg/L）和 30-9200mg/L。替代标本中 GHB 的分析：所有含有水的生物液和组织都适合 GHB 的分析。本文讨论的替代标本的例子有 CSF、唾液、头发、母乳、DBS、VH 和脑组织。
在中毒患者入院或因药物相关犯罪被捕后，必须尽快获得用于分析 GHB 的体液，以提高检测药物的机会。与血液样本相比，尿液采样可将检测窗口延长 3-4 小时，但如果从摄入 GHB 到获得标本的时间延迟较长，则头发、指甲可能是唯一的选择。在死后毒理学中，与血液相比，膀胱尿液、VH 和 CSF 中的药物浓度往往更稳定，因为这些采样部位免受来自肠道的细菌扩散的影响。因此，当调查药物中毒死亡时，GHB 的血液和尿液浓度之间的关系提供了有用的信息。
