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一种用于定量测定人血浆中阿比特龙活性代谢物Δ(4)-阿比特龙(D4A)的液相色谱-串联质谱法。

An LC-MS/MS method for quantification of the active abiraterone metabolite Δ(4)-abiraterone (D4A) in human plasma.

作者信息

van Nuland Merel, Rosing Hilde, de Vries Jelle, Ovaa Huib, Schellens Jan H M, Beijnen Jos H

机构信息

Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands; Division of pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 15;1068-1069:119-124. doi: 10.1016/j.jchromb.2017.10.033. Epub 2017 Oct 16.

Abstract

Δ(4)-Abiraterone (D4A) is a recently discovered active metabolite of the oral anti-androgen drug abiraterone acetate. For quantification of this metabolite in human plasma, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. Human plasma samples of patients treated with abiraterone acetate were prepared by protein precipitation with acetonitrile. The method was validated over a linear range of 0.2-20ng/mL. Intra-assay and inter-assay variabilities were within ±15% of the nominal concentrations for quality control (QC) samples at medium and high concentrations and within ±20% at the lower limit of quantification (LLOQ), respectively. The described method for quantification of D4A was validated successfully and implemented to support therapeutic drug monitoring in patients treated with abiraterone acetate.

摘要

Δ(4)-阿比特龙(D4A)是最近发现的口服抗雄激素药物醋酸阿比特龙的活性代谢产物。为了定量测定人血浆中的这种代谢产物,开发并验证了一种液相色谱-串联质谱(LC-MS/MS)方法。用乙腈进行蛋白沉淀制备接受醋酸阿比特龙治疗患者的人血浆样本。该方法在0.2-20ng/mL的线性范围内得到验证。中、高浓度质量控制(QC)样本的批内和批间变异分别在标称浓度的±15%以内,定量下限(LLOQ)处的变异在±20%以内。所描述的D4A定量方法已成功验证,并用于支持接受醋酸阿比特龙治疗患者的治疗药物监测。

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