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应用快速且高度选择性的 LC-MS/MS 方法进行 16 种药物和代谢物的汗液贴片筛查。

Application of sweat patch screening for 16 drugs and metabolites using a fast and highly selective LC-MS/MS method.

机构信息

*Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, The Netherlands; †SumID-Project, Zorgontwikkeling, Tactus Addiction Medicine, Deventer, The Netherlands; and ‡ACSW-Nijmegen Institute for Scientist-Practitioners in Addiction, Radboud University, Nijmegen, The Netherlands.

出版信息

Ther Drug Monit. 2014 Feb;36(1):35-45. doi: 10.1097/FTD.0b013e3182a04feb.

Abstract

BACKGROUND

To facilitate the monitoring of drug abuse by patients, a method was developed and validated for fast and highly selective screening for amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine, codeine, heroin, 6-monoacteylmorphine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, nicotine, and cotinine in PharmCheck sweat patches. The analysis of sweat patches would provide a noninvasive alternative matrix to urine or blood samples.

METHODS

The sweat patches were extracted during vigorous shaking for 10 minutes with 1.5 mL of 20 mmol/L ammonium formate, pH 7, and methanol (50%:50% vol/vol). The extracts were cleaned up by filtering through Whatman mini-Uniprep syringeless filter vials before injection. The method uses a single injection to detect and confirm all 16 drugs and metabolites within 9.6 minutes.

RESULTS

The validated substances have a linear range of 3.0-300 nanograms per patch, except for nicotine which has a linear range of 30-3750 nanograms per patch. Stabilities of all substances in worn sweat patches were validated at room temperature for 7 days and as a processed sample in the autosampler at 10°C for 5 days. Only heroin was unstable, with high individual variability and reported bias and coefficient of variation of, respectively, -30.6% and 22.1% in worn sweat patches at room temperature. The monitoring of ion ratios was added to the validation criteria. This resulted in analytical cutoff concentrations of 3.0 and 60 nanograms per patch for nicotine with validated qualifier/quantifier ratios. All analytical cutoff concentrations were lower than the cutoff concentrations proposed by the Substance Abuse and Mental Health Services Administration.

CONCLUSIONS

The method uses validated cutoff concentrations, qualifier/quantifier ratios, and a simple extraction without extensive sample treatment for the analysis of 16 drugs and metabolites with a runtime of 9.6 minutes. This method was successfully applied for the analysis of 96 worn sweat patches to monitor patients for drug abuse. The results provided the physician or health-care professional with information about drug abuse and could be used to improve patient care with patient-specific therapy.

摘要

背景

为了方便患者监测药物滥用情况,开发并验证了一种方法,用于快速且高度选择性地筛选安非他命、甲基苯丙胺、3,4-亚甲二氧基甲基苯丙胺、亚甲二氧基苯丙胺、亚甲基二氧乙基苯丙胺、哌醋甲酯、可卡因、苯甲酰爱康宁、吗啡、可待因、海洛因、6-单乙酰吗啡、美沙酮、2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷、尼古丁和可替宁在 PharmCheck 汗液贴片中的含量。汗液贴片的分析为尿液或血液样本提供了一种非侵入性的替代基质。

方法

在剧烈摇晃 10 分钟后,用 1.5 毫升 20mmol/L 甲酸铵、pH7 和甲醇(50%:50%体积/体积)提取汗液贴片。在进样前,通过 Whatman mini-Uniprep 无针注射器滤筒过滤对提取物进行净化。该方法使用单次进样可在 9.6 分钟内同时检测和确认 16 种药物和代谢物。

结果

除尼古丁的线性范围为 30-3750 纳克/贴片外,验证物质的线性范围均为 3.0-300 纳克/贴片。所有在佩戴的汗液贴片中的物质在室温下 7 天和在 10°C 的自动进样器中处理 5 天的稳定性均得到验证。只有海洛因不稳定,个体差异大,报告的偏差和变异系数分别为-30.6%和 22.1%。在室温下佩戴的汗液贴片。在验证标准中增加了离子比的监测。这导致尼古丁的分析截断浓度为 3.0 和 60 纳克/贴片,具有验证的限定符/定量器比。所有分析截断浓度均低于物质滥用和心理健康服务管理局提出的截断浓度。

结论

该方法使用验证的截断浓度、限定符/定量器比和简单的提取方法,无需广泛的样品处理,即可在 9.6 分钟内分析 16 种药物和代谢物。该方法成功应用于 96 个佩戴的汗液贴片分析,以监测患者的药物滥用情况。结果为医生或医疗保健专业人员提供了药物滥用信息,并可用于通过针对患者的治疗来改善患者护理。

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