Nordal Kristin, Øiestad Elisabeth L, Enger Asle, Christophersen Asbjorg S, Vindenes Vigdis
*Department of Clinical Pharmacology, Oslo University Hospital HF, Rikshospitalet; †Department of Drug Abuse Research and Method Development, Division of Forensic Sciences, Norwegian Institute of Public Health; and ‡Emergency Department for Addictive Disorders, Oslo University Hospital HF, Aker, Oslo, Norway.
Ther Drug Monit. 2015 Aug;37(4):451-60. doi: 10.1097/FTD.0000000000000174.
Clonazepam, diazepam, and alprazolam are benzodiazepines with sedative, anticonvulsant, and anxiolytic effects, but their prevalence in drug abuse and drug overdoses has long been recognized. When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid collected from imprisoned persons might lead to negative sanctions, and the knowledge of detection times of these drugs is thus important to ensure correct interpretation. The aim of this study was to investigate the time window of detection for diazepam, clonazepam, and alprazolam in oral fluid from drug addicts admitted to detoxification.
Twenty-five patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid was collected daily in the morning and the evening and urine samples every morning for 10 days, using the Intercept device. Whole blood samples were collected if the patient accepted. The cutoff levels in oral fluid were 1.3 ng/mL for diazepam, N-desmethyldiazepam, and 7-aminoclonazepam and 1 ng/mL for clonazepam and alprazolam. In urine, the cutoff levels for quantifications were 30 ng/mL for alprazolam, alpha-OH-alprazolam, and 7-aminoclonazepam, 135 ng/mL for N-desmethyldizepam, and 150 ng/mL for 3-OH-diazepam and for all the compounds, the cutoff for the screening analyses were 200 ng/mL.
The maximum detection times for diazepam and N-desmethyldiazepam in oral fluid were 7 and 9 days, respectively. For clonazepam and 7-aminoclonazepam, the maximum detection times in oral fluid were 5 and 6 days, respectively. The maximum detection time for alprazolam in oral fluid was 2.5 days. New ingestions were not suspected in any of the cases, because the corresponding concentrations in urine were decreasing. Results from blood samples revealed that high doses of benzodiazepines had been ingested before admission, and explains the longer detection times in oral fluids than reported previously after intake of therapeutic doses of these drugs.
This study has shown that oral fluid might be a viable alternative medium to urine when the abuse of benzodiazepines is suspected.
氯硝西泮、地西泮和阿普唑仑是具有镇静、抗惊厥和抗焦虑作用的苯二氮䓬类药物，但它们在药物滥用和药物过量中的流行情况早已为人所知。当报告口腔液中精神活性药物的检测时间时，它们大多基于临床研究中给予的治疗剂量。然而，如药物滥用后所见的重复高剂量摄入很可能导致长时间的阳性样本。从被监禁者收集的口腔液中发现滥用药物可能会导致负面制裁，因此了解这些药物的检测时间对于确保正确解读很重要。本研究的目的是调查戒毒所收治的吸毒成瘾者口腔液中地西泮、氯硝西泮和阿普唑仑的检测时间窗。
纳入25名有重度药物滥用史且入住戒毒病房的患者。使用Intercept装置，每天早晚收集口腔液，连续10天每天早上收集尿液样本。如果患者同意，则收集全血样本。口腔液中地西泮、N-去甲地西泮和7-氨基氯硝西泮的截断水平为1.3 ng/mL，氯硝西泮和阿普唑仑的截断水平为1 ng/mL。在尿液中，阿普唑仑、α-羟基阿普唑仑和7-氨基氯硝西泮定量的截断水平为30 ng/mL，N-去甲地西泮为135 ng/mL，3-羟基地西泮为150 ng/mL，所有化合物的筛查分析截断水平为200 ng/mL。
口腔液中地西泮和N-去甲地西泮的最长检测时间分别为7天和9天。氯硝西泮和7-氨基氯硝西泮在口腔液中的最长检测时间分别为5天和6天。口腔液中阿普唑仑的最长检测时间为2.5天。由于尿液中相应浓度在下降，所有病例均未怀疑有新的摄入情况。血样结果显示，入院前曾摄入高剂量苯二氮䓬类药物，这解释了口腔液中的检测时间比先前报告的这些药物治疗剂量摄入后的检测时间更长。
本研究表明，当怀疑存在苯二氮䓬类药物滥用时，口腔液可能是尿液的一种可行替代介质。
