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用于定量豚鼠血浆中纳曲酮和6β-纳曲醇的液相色谱-质谱法的开发与验证

Development and validation of a liquid chromatography-mass spectrometry method for the quantitation of naltrexone and 6beta-naltrexol in guinea pig plasma.

作者信息

Valiveti Satyanarayana, Nalluri Buchi N, Hammell Dana C, Paudel Kalpana S, Stinchcomb Audra L

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Oct 25;810(2):259-67. doi: 10.1016/j.jchromb.2004.08.016.

DOI:10.1016/j.jchromb.2004.08.016
PMID:15380723
Abstract

A quantitative liquid chromatographic-electrospray ionization mass spectrometry method for the determination of naltrexone and 6beta-naltrexol in guinea pig plasma has been developed and validated using naloxone as an internal standard. A single step precipitation-extraction technique was carried out to extract the plasma samples using acetonitrile:ethyl acetate (1:1, v/v). The chromatographic separation was performed on a C(18) column using a mobile phase consisting of 35:65 (v/v) acetonitrile:2 mM ammonium acetate with 0.01 mM ammonium citrate at a flow rate of 0.25 mL/min. The analyte was detected after positive electrospray ionization using selected ion monitoring (SIM) mode. The mean recoveries for naltrexone, naltrexol, and naloxone were 91.7, 89.3, and 99.0%, respectively. The lower limit of quantification (LLOQ) for naltrexone and 6beta-naltrexol was 1.25 ng/mL, and the limit of detection (LOD) was 0.75 ng/mL. The method was applied to a pharmacokinetic study in order to assess the drug disposition of naltrexone in guinea pigs.

摘要

已建立并验证了一种定量液相色谱 - 电喷雾电离质谱法,用于测定豚鼠血浆中的纳曲酮和6β - 纳曲醇,采用纳洛酮作为内标。采用一步沉淀 - 萃取技术,使用乙腈:乙酸乙酯(1:1,v/v)萃取血浆样品。色谱分离在C(18)柱上进行,流动相由35:65(v/v)乙腈:2 mM乙酸铵与0.01 mM柠檬酸铵组成,流速为0.25 mL/min。使用选择离子监测(SIM)模式在正电喷雾电离后检测分析物。纳曲酮、纳曲醇和纳洛酮的平均回收率分别为91.7%、89.3%和99.0%。纳曲酮和6β - 纳曲醇的定量下限(LLOQ)为1.25 ng/mL,检测限(LOD)为0.75 ng/mL。该方法应用于药代动力学研究,以评估纳曲酮在豚鼠体内的药物处置情况。

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