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采用液相色谱串联质谱法测定小体积样本中的吗啡、芬太尼及其代谢物。

Determination of Morphine, Fentanyl and Their Metabolites in Small Sample Volumes Using Liquid Chromatography Tandem Mass Spectrometry.

机构信息

Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, 148TF, Boston, 02115 MA, USA.

出版信息

J Anal Toxicol. 2020 May 18;44(4):325-330. doi: 10.1093/jat/bkz104.

DOI:10.1093/jat/bkz104
PMID:31897488
Abstract

The USA and numerous other countries worldwide are currently experiencing a public health crisis due to the abuse of heroin and illicitly manufactured fentanyl. We have developed a liquid chromatography tandem mass spectrometry (LC-MS-MS)-based method for the detection of morphine, fentanyl and their metabolites, including morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), normorphine, norfentanyl and deuterated internal standards in limited sample volumes with the limit of detection of 5.0/0.5 ng/mL (morphine, M3G, M6G, normorphine/fentanyl, norfentanyl). The inter-assay precision (%CV) was less than 12% for all assays, and the inter-assay bias (%) was less than 5%. The ruggedness of the method, dilution effect and carryover were also investigated as part of the study. The simultaneous quantification of morphine, fentanyl and its metabolites via this simple and time- and cost-efficient method could be successfully applied to samples taken for pharmacokinetic evaluation (antemortem and postmortem) after a single dose of morphine or co-administration of morphine with other drugs (e.g., fentanyl) in rats.

摘要

由于海洛因和非法制造的芬太尼滥用,美国和世界上许多其他国家目前正面临一场公共卫生危机。我们开发了一种基于液相色谱串联质谱(LC-MS-MS)的方法,用于检测吗啡、芬太尼及其代谢物,包括吗啡-3-葡糖苷酸(M3G)、吗啡-6-葡糖苷酸(M6G)、去甲吗啡、去甲芬太尼和内标物(氘代),在有限的样品体积下检测限为 5.0/0.5 ng/mL(吗啡、M3G、M6G、去甲吗啡/芬太尼、去甲芬太尼)。所有分析物的批内精密度(%CV)均小于 12%,批间偏差(%)均小于 5%。该方法的耐用性、稀释效应和交叉污染也作为研究的一部分进行了考察。通过这种简单、省时、高效的方法,可同时定量检测吗啡、芬太尼及其代谢物,成功应用于单次吗啡给药或吗啡与其他药物(如芬太尼)联合给药后(如生前和死后)的药代动力学评估样本。

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