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Supercritical fluid chromatography-tandem mass spectrometry for high throughput bioanalysis of small molecules in drug discovery
Liquid 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 studies correlated very well between the data produced by SFC-MS/MS and LC?MS/MS. Approximately 95% samples tested had ?25% difference between SFC-MS/MS and LC?MS/MS data. It was demonstrated that SFC-MS/MS was comparable to golden standard LC?MS/MS and was an alternative choice for routine high throughput bioanalysis of small molecule drugs.
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data.Safety of Atorvastatin lactone, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 125995-03-1, in my other articles.
Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics