Wang Xin, Johansen Sys Stybe, Zhang Yurong, Jia Jingying, Rao Yulan, Jiang Fengli, Linnet Kristian
Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's Vej 11, 2100, Copenhagen, Denmark.
Shanghai Key Laboratory of Crime Scene Evidence, Shanghai Institute of Forensic Science, 803 Zhong Shan Bei Yi Road, Shanghai, 200083, People's Republic of China.
Int J Legal Med. 2017 Jan;131(1):131-141. doi: 10.1007/s00414-016-1429-x. Epub 2016 Aug 17.
Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.
关于单次服用地西泮及其某些代谢物(去甲地西泮、奥沙西泮和替马西泮)后毛发中的浓度,仅有零星数据。本研究的目的是调查8名健康志愿者(4名女性和4名男性,年龄24 - 26岁,东亚人)服用10毫克地西泮后,地西泮及其代谢物在人发中的沉积情况。暴露1个月后从所有志愿者处采集毛发,男性在暴露2个月后、女性在暴露10个月后再次采集毛发。采用超高压液相色谱 - 串联质谱法(UHPLC - MS/MS)测定地西泮及完整的代谢物谱,包括奥沙西泮葡萄糖醛酸苷和替马西泮葡萄糖醛酸苷,地西泮、去甲地西泮、奥沙西泮和替马西泮的定量限(LOQ)为0.5 - 2.5 pg/mg,奥沙西泮葡萄糖醛酸苷和替马西泮葡萄糖醛酸苷的定量限为10 pg/mg。所发现的地西泮或代谢物的量在性别上没有差异。服用后1个月和2个月时,主要代谢物去甲地西泮的浓度始终高于地西泮。在一些志愿者的毛发中发现了奥沙西泮和替马西泮的痕量,但未检测到葡萄糖醛酸苷。暴露10个月后地西泮和去甲地西泮的水平极低(接近定量限),表明因个人卫生和身体接触导致药物损失。据我们所知,这是第一项使用黑发进行的单剂量地西泮研究,也是第一项在人发中测量奥沙西泮葡萄糖醛酸苷和替马西泮葡萄糖醛酸苷的研究。