A mass spectrometry quantitation technique enables high-throughput quantitation of small molecules using a laser-desorption (e.g., MALDI) ion source coupled to a triple-quadrupole mass analyzer. The ions generated from the ion source are collisionally damped/cooled, and then quantitatively analyzed using the triple-quadrupole analyzer operated in the multiple-reaction-monitoring (MRM) mode. Significantly improved measurement throughput is obtained by applying the laser to each sample spot on the target for an irradiation duration significantly shorter than the time required to deplete the sample material in the sample spot. The irradiation duration may be set based on a determination of the MRM peak broadening caused by the ion optics. This allows significantly reduced widths of the MRM peaks while maintaining good signal to noise ratios and provides a significantly improved throughput of the quantitation analyses as well as improved reproducibility of the MRM peaks and reduced compound dependence of the MRM peak widths.