Supercritical fluid chromatography-tandem mass spectrometry for high throughput bioanalysis of small molecules in drug discovery

Publication date: Available online 13 October 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Xiaolin Zhang, Xiao Ding, Jianshuang Wang, Brian DeanAbstractLiquid chromatography tandem mass spectrometry (LC-MS/MS) has been a golden standard for high throughput small molecule bioanalysis in drug discovery for decades. Supercritical fluid chromatography (SFC) has caught more attention in recent decade due to its advantages of greener mobile phase, lower backpressure and higher separation power. For the first time, we evaluated supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) as a high throughput technique for bioanalysis of small molecule drug candidates and compared it to reversed phase LC-MS/MS. Twenty five compounds with diversified structures were evaluated using combination of 6 achiral columns and 4 different mobile phase compositions. To be able to make direct comparison between SFC and HPLC, same type of mass spectrometer was used as the detector. Extracted biological samples were injected to an SFC-MS/MS system and then re-injected to an LC-MS/MS system. It was found that the success rate of the SFC-MS/MS method development was more than 95% if using certain combinations of achiral column and mobile phase compositions without the time-consuming method scouting process. Sensitivity was established between 0.1 to 5.0 ng/mL for both SFC-MS/MS and LC-MS/MS with better sensitivity on SFC-MS/MS. Data from application studi...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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