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加速器质谱:其作为一线生物分析技术的作用。

Accelerator MS: its role as a frontline bioanalytical technique.

作者信息

Seymour Mark A

机构信息

Xceleron, York Biocentre, Innovation Way, York, UK.

出版信息

Bioanalysis. 2011 Dec;3(24):2817-23. doi: 10.4155/bio.11.285.

DOI:10.4155/bio.11.285
PMID:22185281
Abstract

Accelerator MS (AMS) is an ultrasensitive technique that can be used to quantify (14)C in biological samples. Prior to analysis, the carbon in samples is selectively isolated, with the result that the technique is independent of compound structure and nonsusceptible to matrix effects. AMS is a tracer technique and therefore can be used to quantify all compound-related material without the need to develop extraction or chromatographic separation methods. Thus AMS has some distinct advantages over conventional assay techniques, such as LC-MS/MS. AMS also complements conventional techniques, facilitating innovative, cost-effective clinical study designs. Thus, metabolism data can be obtained from early clinical trials, identifying any human metabolites that may raise safety concerns. By administration of an intravenous (14)C microtracer dose concomitantly with an extravascular dose of nonradiolabeled compound, AMS can also be used to determine absolute bioavailability and intravenous pharmacokinetic parameters without the need for intravenous toxicology or formulation development.

摘要

加速器质谱法(AMS)是一种超灵敏技术,可用于定量生物样品中的¹⁴C。在分析之前,样品中的碳被选择性分离,结果是该技术独立于化合物结构且不受基质效应影响。AMS是一种示踪技术,因此可用于定量所有与化合物相关的物质,而无需开发提取或色谱分离方法。因此,与传统分析技术(如液相色谱-串联质谱法(LC-MS/MS))相比,AMS具有一些明显优势。AMS还可补充传统技术,促进创新、具有成本效益的临床研究设计。因此,可从早期临床试验中获得代谢数据,识别任何可能引发安全问题的人体代谢物。通过静脉注射¹⁴C微量示踪剂剂量并同时给予非放射性标记化合物的血管外剂量,AMS还可用于确定绝对生物利用度和静脉药代动力学参数,而无需进行静脉毒理学或制剂开发。

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