Highly Sensitive Pharmaceutical and Clinical Analysis Using Selective Solid-Phase Extraction Coupled to Microflow Liquid Chromatography and Isotope-Dilution Mass Spectrometry

摘要: The capacity of ultrasensitive quantification is highly desirable in many clinical and pharmaceutical applications, such as the PK study low-dose administration low-abundance markers circulating systems. Nonetheless, this task challenging even for a LC-MS/MS approach, due to extremely low levels analytes complex matrices. Here we describe robust method therapeutic agents or biological This achieved by combination selective solid-phase extraction (SPE) with sensitive capillary LC (μLC)-MS/MS analysis. Comparing conventional LC-MS/MS, μLC-MS/MS provides much higher sensitivity lower peak dilution. SPE washing elution conditions were optimized so that target drugs are selectively extracted from matrix. By eliminating most undesirable matrix components, procedure enabled high sample loading volume on μLC column without compromising chromatographic performance operational robustness, helped achieve ultralow detection limits. Sufficient separation was employed order further improve analytical decrease effects. To show application strategy, three paradigms, respectively, quantifications (1) corticosteroids after an intravitreous injection, (2) anticancer agent treatment, (3) several vitamin D (VitD) metabolites plasma, introduced chapter. Typically, pg/mL LOQ achieved, linearity, accuracy, precision these developed methods excellent.