Mass
spectrometry (MS) in hyphenated techniques is widely accepted
as the gold standard quantitative tool in life sciences. However,
MS possesses intrinsic analytical capabilities that allow it to be
a stand-alone quantitative technique, particularly with current technological
advancements. MS has a great potential for simplifying quantitative
analysis without the need for tedious chromatographic separation.
Its selectivity relies on multistage MS analysis (MSn),
including tandem mass spectrometry (MS/MS), as well as the ever-growing
advancements of high-resolution MS instruments. This perspective describes
various analytical platforms that utilize MS as a stand-alone quantitative
technique, namely, flow injection analysis (FIA), matrix assisted
laser desorption ionization (MALDI), including MALDI-MS imaging and
ion mobility, particularly high-field asymmetric waveform ion mobility
spectrometry (FAIMS). When MS alone is not capable of providing reliable
quantitative data, instead of conventional liquid chromatography (LC)-MS,
the use of a guard column (i.e., fast chromatography) may be sufficient
for quantification. Although the omission of chromatographic separation
simplifies the analytical process, extra procedures may be needed
during sample preparation and clean-up to address the issue of matrix
effects. The discussion of this manuscript focuses on key parameters
underlying the uniqueness of each technique for its application in
quantitative analysis without the need for a chromatographic separation.
In addition, the potential for each analytical strategy and its challenges
are discussed as well as improvements needed to render them as mainstream
quantitative analytical tools. Overcoming the hurdles for fully validating
a quantitative method will allow MS alone to eventually become an
indispensable quantitative tool for clinical and toxicological studies.