School of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China.
Key Laboratory of Forensic Toxicology of Ministry of Public Security, Jinzhong, 030600, Shanxi, China.
Drugs R D. 2022 Mar;22(1):43-50. doi: 10.1007/s40268-021-00375-y. Epub 2022 Jan 31.
Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine.
This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants.
A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography-tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model.
Urinary diazepam peaked at 2.38 ng/mL (C) and 1.93 h (T). The urinary metabolite nordiazepam peaked at 1.17 ng/mL and 100.21 h; temazepam glucuronide (TG) peaked at 145.61 ng/mL and 41.14 h; and oxazepam glucuronide (OG) peaked at 101.57 ng/mL and 165.86 h. The elimination half-life (t) and clearance (CLz/F) for diazepam were 119.58 h and 65.77 L/h, respectively. The t of the metabolites nordiazepam, TG, and OG was 310.58 h, 200.17 h, and 536.44 h, respectively. Finally, this study found that both diazepam and its main metabolites in urine were detectable for at least 15 days, although there were individual differences.
The results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening.
尿液通常被用作记录地西泮相关犯罪的样本；然而，很少有报道描述地西泮及其代谢物在尿液中的药代动力学。
本研究旨在研究地西泮及其代谢物，包括葡萄糖醛酸化合物，在中国参与者尿液中的药代动力学。
共招募 28 名志愿者，每名志愿者口服 5 毫克地西泮。从每位志愿者摄入后时间点（零）、1、2、4、8、12 和 24 小时以及 2、3、6、12 和 15 天收集 10 毫升尿液。所有样品均通过固相萃取提取，并采用高效液相色谱-串联质谱法分析。志愿者尿液中检测到地西泮及其主要代谢物（替马西泮除外）。采用非房室模型的药代动力学软件 DAS 分析药代动力学参数。
尿中地西泮 C 最大浓度为 2.38ng/mL，T 最大浓度为 1.93 小时。代谢物去甲基地西泮 C 最大浓度为 1.17ng/mL，T 最大浓度为 100.21 小时；替马西泮葡萄糖醛酸（TG）C 最大浓度为 145.61ng/mL，T 最大浓度为 41.14 小时；奥沙西泮葡萄糖醛酸（OG）C 最大浓度为 101.57ng/mL，T 最大浓度为 165.86 小时。地西泮的消除半衰期（t）和清除率（CLz/F）分别为 119.58 小时和 65.77L/h。去甲基地西泮、TG 和 OG 的 t 分别为 310.58 小时、200.17 小时和 536.44 小时。最后，本研究发现，地西泮及其主要代谢物在尿液中至少可检测到 15 天，尽管存在个体差异。
地西泮在尿液中的药代动力学结果将对法医学和药物筛查有很大帮助。
