Stability, robustness and time efficiency are three major challenges in laboratories where a large number of samples are analyzed routinely. Here we report usability study of a new two channels HPLC, a new tandem mass spectrometer and a new data processing software to address these challenges. A total of 2,000 crashed synthetic serum samples spiked with Alprazolam and isotopic internal standard were analyzed continuously over 100 hours, with additional 44 QC samples. Instrument-to-instrument precision studies (3 units) are reported with four example compounds (Reserpine, Chloramphenicol, Testosterone, Estradiol) using both HESI probe and APCI probe in both positive and negative ionization modes.