Introduction Rapid development of quantitative LC-MS/MS assays for bioanalytical application is often slowed down by memory effects due to ion scattering in the mass spectrometer, following optimization by infusional analysis at high analyste concentrations. This can be particularly problematical for drugs with detection limits in the sub ng/mL range, where it may take several hours for background levels decline to acceptable levels. Use of high LC flow rate can also cause high chemical background due to inefficient desolvation, which over time, can cause system contamination necessitating maintenance and interrupt the continuous operation of the mass spectrometer that is required for high throughput analysis. Here, we evaluated the application and performance a new high signal-to-noise atmospheric pressure interface, HSID. This new interface very effectively focuses target analyte ions through orthogonal samp領, such that memory effects are minimal. In addition, it has been designed to improve sensitivity at high LC flows by reducing background chemical noise, through better desolvation by using energy transfer of heated gas as ions flow through moderate pressure laminar flow regions of the interface.