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采用液相色谱/串联质谱法测定毛发样本中的阿片类镇痛药及其在姑息治疗患者中的应用。

Determination of opioid analgesics in hair samples using liquid chromatography/tandem mass spectrometry and application to patients under palliative care.

作者信息

Musshoff Frank, Lachenmeier Katrin, Trafkowski Jens, Madea Burkhard, Nauck Friedemann, Stamer Ulrike

机构信息

Institute of Forensic Medicine, University of Bonn, Bonn, Germany.

出版信息

Ther Drug Monit. 2007 Oct;29(5):655-61. doi: 10.1097/FTD.0b013e318155a329.

Abstract

Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple methanolic extraction, and the evaporated extract was analyzed directly. A selective and sensitive procedure for the simultaneous determination of bisnortilidine, nortilidine, tilidine, buprenorphine, codeine, oxycodone, fentanyl, norfentanyl, hydromorphone, morphine, normorphine, oxymorphone, methadone, piritramide, and tramadol was developed and fully validated. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection ranging from 0.008 to 0.017 ng/mg hair matrix, and precision ranging between 3.1% and 14.9 %. The applicability of the method was shown by analysis of authentic hair samples from patients receiving opioids for the treatment of cancer pain (eg, fentanyl was detected in concentrations up to 0.292 ng/mg, tramadol in concentrations up to 0.612 ng/mg of hair of 1 patient). Hair analysis was shown to be a complementary and useful tool in monitoring the drug-taking behavior of patients consuming opioid analgesics for the treatment of pain. In self-reports and medical records especially, the ingestion of tramadol and methadone was found to be dramatically underreported. In summary, hair analyses gave important additional information for the medical treatment of patients, the results often coming as a surprise to even the attending physicians.

摘要

毛发检测程序能够累积反映长期药物滥用情况,在临床毒理学中作为一种合规性检测手段很有用。在本研究中,采用液相色谱-串联质谱法测定毛发样本中的阿片类镇痛药物。该程序采用简单的甲醇提取法,蒸发后的提取物直接进行分析。开发并全面验证了一种同时测定双去甲替利定、去甲替利定、替利定、丁丙诺啡、可待因、羟考酮、芬太尼、去甲芬太尼、氢吗啡酮、吗啡、去甲吗啡、羟吗啡酮、美沙酮、匹利卡明和曲马多的选择性灵敏程序。该方法符合验证标准,灵敏度高,毛发基质的检测限为0.008至0.017 ng/mg,精密度在3.1%至14.9%之间。通过分析接受阿片类药物治疗癌症疼痛患者的真实毛发样本,证明了该方法的适用性(例如,在1名患者的毛发中检测到芬太尼浓度高达0.292 ng/mg,曲马多浓度高达0.612 ng/mg)。毛发分析被证明是监测服用阿片类镇痛药治疗疼痛患者用药行为的一种补充且有用的工具。特别是在自我报告和医疗记录中,发现曲马多和美沙酮的摄入量被严重低估。总之,毛发分析为患者的医疗提供了重要的额外信息,其结果往往甚至会让主治医生感到惊讶。

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