Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 May 1;879(15-16):1098-104. doi: 10.1016/j.jchromb.2011.03.026. Epub 2011 Mar 21.
We report the development of a sensitive liquid chromatography-tandem mass spectrometric assay to quantitate 3-methoxysalicylamine (3-MoSA) in biological samples. Derivatization with 1,1'-thiocarbonyldiimidazole followed by C(18) reverse-phase chromatography allowed the detection of both analyte and internal standard (hexylsalicylamine) using electrospray ionization and selected reaction monitoring (SRM) in positive ion mode. We monitored the transitions from m/z 196.7 to 65.1 and from m/z 250.1 to 77.1 for 3-MoSA and HxSA, respectively. The method is validated with respect to linearity (r(2)=0.995), precision (<17% RSD), recovery (100% for 3-MoSA and HxSA), and stability (77% after storage up to 7 month at -80°C). The LOD and LOQ were 16.12 and 48.87 μg/l, respectively and the LLOQ of 1 pg/ml. In addition, we used this assay to analyze the pharmacokinetics of 3-MoSA in mouse plasma and tissues following both intraperitoneal and oral administration, providing new information regarding the distribution of this compound in vivo.
我们开发了一种灵敏的液相色谱-串联质谱分析方法，用于定量生物样品中的 3-甲氧基水杨酰胺（3-MoSA）。用 1,1'-硫代羰基二咪唑衍生化，然后进行 C(18)反相色谱分离，在正离子模式下采用电喷雾电离和选择反应监测（SRM），可以同时检测到分析物和内标（己基水杨酰胺）。我们分别监测了 m/z 196.7 到 65.1 和 m/z 250.1 到 77.1 的跃迁，用于 3-MoSA 和 HxSA。该方法在线性（r(2)=0.995）、精密度（<17% RSD）、回收率（3-MoSA 和 HxSA 均为 100%）和稳定性（在-80°C 下储存长达 7 个月后为 77%）方面均得到验证。LOD 和 LOQ 分别为 16.12 和 48.87 μg/l，LLOQ 为 1 pg/ml。此外，我们还使用该方法分析了腹腔内和口服给药后 3-MoSA 在小鼠血浆和组织中的药代动力学，提供了关于该化合物在体内分布的新信息。
