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高效液相色谱-串联质谱法分析大鼠血浆中的 2-巯基乙磺酸钠。

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry.

机构信息

Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, South Dakota 57007, USA.

Department of Pediatrics-Pulmonary and Sleep Medicine Section, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Jan 15;1189:123088. doi: 10.1016/j.jchromb.2021.123088. Epub 2021 Dec 22.

Abstract

Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide). Also, it scavenges free radicals which cause numerous disorders by attacking biological molecules. Current methods available to analyze MESNA in biological matrices include colorimetry and high-performance liquid chromatography (HPLC) with ultraviolet, fluorescence, or electrochemical detection. These methods have several limitations including low sensitivity, poor selectivity, a high degree of difficulty, and long analysis times. Hence, a rapid, simple, and sensitive HPLC tandem mass spectrometry (MS/MS) method was developed and validated to quantify MESNA in rat plasma following IP administration. The analysis of MESNA was accomplished via plasma protein precipitation, centrifugation, supernatant evaporation, reconstitution, and HPLC-MS/MS analysis. The method showcases an outstanding limit of detection (20 nM), excellent linearity (R = 0.999, and percent residual accuracy >90%) and a wide linear range (0.05-200 μM). The method also produced good accuracy and precision (100 ± 10% and <10% relative standard deviation, respectively). The validated method was successfully used to analyze MESNA from treated animals and will allow easier development of MESNA for therapeutic purposes.

摘要

2-巯基乙磺酸单钠盐(MESNA)是一种含硫醇的化合物,已被证明能有效灭活某些抗癌药物(如环磷酰胺和异环磷酰胺)的毒性代谢物丙烯醛。此外,它还能清除自由基,自由基通过攻击生物分子会导致多种疾病。目前分析生物基质中 MESNA 的方法包括比色法和高效液相色谱法(HPLC),检测手段有紫外、荧光或电化学。这些方法存在灵敏度低、选择性差、难度大、分析时间长等局限性。因此,建立并验证了一种快速、简单、灵敏的 HPLC 串联质谱(MS/MS)法,用于检测腹腔注射 MESNA 后大鼠血浆中的 MESNA。通过血浆蛋白沉淀、离心、上清液蒸发、复溶和 HPLC-MS/MS 分析来完成 MESNA 的分析。该方法的检测限低(20 nM),线性度好(R=0.999,残留准确度大于 90%),线性范围宽(0.05-200 μM)。方法的准确度和精密度也很好(100±10%和<10%相对标准偏差)。验证后的方法成功地用于分析治疗动物中的 MESNA,将有助于开发 MESNA 用于治疗目的。

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