The Q Exactive MS is well suited for targeted quantification providing two powerful HR/AM approaches, msx tSIM and tHCD. Both approaches demonstrate high selectivity, high sensitivity and high throughput due to several hardware and software innovations. ? For the msx tSIM approach, high mass accuracy (< 5 ppm) and high resolution (140K) ensures accurate identification of target ions in the presence of complex background, while spectrum multiplexing dramatically increases throughput without sacrificing resolution. ? A LOD of 10 amol and 4-order linear dynamic range was obtained for most peptides with msx tSIM method in the presence of medium complex background. ? Different from triple-quadrupole-based SRM, all fragment ions are simultaneously detected with high mass accuracy and high resolution using the tHCD approach. The HR/AM of fragment ions provides unmatched selectivity. The simultaneous detection of all fragment ions allows more efficient sampling of target peptides and results in improved sensitivity. A scan speed of 12 Hz at a resolution of 17,500 ensures high throughput. ? A LOD of 50 amol and 3-4 orders linear dynamic range was obtained for most peptides with tHCD method in the presence of strong complex background.