Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry.
Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry.
复制标题
DOI：
10.1016/j.jchromb.2014.01.006
复制
发表时间：
2014-02-15
影响因子：
3
通讯作者：
Logue, Brian A.
中科院分区：
文献类型：
--
作者：
Stutelberg, Michael W.;Vinnakota, Chakravarthy V.;Mitchell, Brendan L.;Monteil, Alexandre R.;Patterson, Steven E.;Logue, Brian A.
意外或故意的氰化物中毒是严重的健康风险。目前 FDA 批准的一系列解毒剂，包括羟钴胺、亚硝酸钠和硫代硫酸钠，是有效的，但每种解毒剂都有特定的主要局限性，例如有效剂量大或起效延迟。因此，正在研究下一代氰化物解毒剂以减轻这些限制。其中一种解毒剂 3-巯基丙酮酸 (3-MP) 通过充当硫供体将氰化物转化为硫氰酸盐（一种相对无毒的氰化物代谢物）来解毒氰化物。能够检测生物体液中 3-MP 的分析方法对于开发 3-MP 作为潜在解毒剂至关重要。因此，建立了高效液相色谱串联质谱（HPLC-MS-MS）分析兔血浆中3-MP的方法。样品制备包括用内标 (13C3-3-MP) 掺入血浆、沉淀血浆蛋白以及与一溴二甲胺反应以抑制 3-MP 的特征性二聚化。该方法的检测限为 0.1 µM，线性动态范围为 0.5–100 µM，具有出色的线性度 (R2 ≥ 0.999)、准确度（标称浓度的 ±9%）和精密度（<7% 相对标准偏差）。优化的 HPLC-MS-MS 方法能够检测暴露于氰化物后服用 sulfanegen（3-MP 的前药）的兔子体内的 3-MP。考虑到该方法的优异性能，将用于进一步研究这种有前途的氰化物解毒剂。
Accidental or intentional cyanide poisoning is a serious health risk. The current suite of FDA approved antidotes, including hydroxocobalamin, sodium nitrite, and sodium thiosulfate is effective, but each antidote has specific major limitations, such as large effective dosage or delayed onset of action. Therefore, next generation cyanide antidotes are being investigated to mitigate these limitations. One such antidote, 3-mercaptopyruvate (3-MP), detoxifies cyanide by acting as a sulfur donor to convert cyanide into thiocyanate, a relatively nontoxic cyanide metabolite. An analytical method capable of detecting 3-MP in biological fluids is essential for the development of 3-MP as a potential antidote. Therefore, a high performance liquid chromatography tandem mass spectrometry (HPLC-MS-MS) method was established to analyze 3-MP from rabbit plasma. Sample preparation consisted of spiking the plasma with an internal standard (13C3-3-MP), precipitation of plasma proteins, and reaction with monobromobimane to inhibit the characteristic dimerization of 3-MP. The method produced a limit of detection of 0.1 µM, a linear dynamic range of 0.5–100 µM, along with excellent linearity (R2 ≥ 0.999), accuracy (±9% of the nominal concentration) and precision (<7% relative standard deviation). The optimized HPLC-MS-MS method was capable of detecting 3-MP in rabbits that were administered sulfanegen, a prodrug of 3-MP, following cyanide exposure. Considering the excellent performance of this method, it will be utilized for further investigations of this promising cyanide antidote.
登录
查看更多内容
影响因子：
4.3
作者：
Bhandari, Raj K.;Oda, Robert P.;Logue, Brian A.
通讯作者：
Logue, Brian A.
影响因子：
7.3
作者：
Nagasawa, Herbert T.;Goon, David J. W.;Patterson, Steven E.
通讯作者：
Patterson, Steven E.
影响因子：
5.6
作者：
Spallarossa, A;Forlani, F;Bordo, D
通讯作者：
Bordo, D
影响因子：
4.1
作者：
Cambal, Leah K.;Swanson, Megan R.;Peterson, Jim
通讯作者：
Peterson, Jim
影响因子：
6.2
作者：
Borron, Stephen W.;Baud, Frederic J.;Bismuth, Chantal
通讯作者：
Bismuth, Chantal