Liquid chromatography-mass spectrometry (LC/MS) couples high resolution chromatographic separation with MS detection.  As the system adopts the high separation of HPLC, analytes which are in the liquid mobile phase are often ionized by various soft ionization methods including atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI), which attains the gas phase ionization required for the coupling with MS. These ionization methods allow the analysis of a wider range of biological molecules, including those with larger masses, thermally unstable or nonvolatile compounds where GC-MS is typically incapable of analyzing.
LC-MS provides high selectivity as unresolved peaks can be isolated by selecting a specific mass. Furthermore, better identification is also attained by mass spectra and the user does not have to rely solely on the retention time of analytes. As a result, molecular mass and structural information as well as quantitative data can all be obtained via LC-MS. LC-MS can therefore be applied to various fields, such as impurity identification and profiling in drug development and pharmaceutical manufacturing, since LC provides efficient separation of impurities and MS provides structural characterization for impurity profiling.
Common solvents used in normal or reversed phase LC such as water, acetonitrile, and methanol are all compatible with ESI, yet a LC grade solvent may not be suitable for MS. Furthermore, buffers containing inorganic ions should be avoided as they may contaminate the ion source. Nonetheless, the problem can be resolved by 2D LC-MS, as well as other various issues including analyte coelution and UV detection responses.