- Liquid Chromatography – Mass Spectrometry (LC-MS) is a powerful analytical technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry.
- It is widely used in fields such as proteomics, metabolomics, pharmaceutical development, environmental analysis, and clinical diagnostics because it allows the identification, quantification, and structural characterization of complex mixtures with high sensitivity and specificity.
- In the LC component, compounds are separated based on their physicochemical properties, such as polarity, hydrophobicity, or charge, as they pass through a chromatographic column under high-pressure liquid flow. Different stationary phases and mobile phase gradients can be applied to optimize separation for a wide variety of analytes. The resulting chromatographic peaks represent temporally resolved fractions of the sample, reducing chemical complexity before entering the mass spectrometer.
- Once eluted, analytes are introduced into the mass spectrometer, typically via ionization methods such as electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI). These techniques convert neutral molecules into gas-phase ions under atmospheric pressure conditions, which are then directed into the mass analyzer. The mass spectrometer measures the mass-to-charge ratio (m/z) of the ions, enabling detection of even minute amounts of compounds with high accuracy. Depending on the analyzer type—quadrupole, time-of-flight (TOF), orbitrap, or ion trap—different levels of resolution, speed, and mass accuracy can be achieved.
- One of the major strengths of LC-MS is its versatility in qualitative and quantitative applications. It enables untargeted discovery studies, such as profiling metabolites in biological samples, as well as targeted analyses, such as quantifying specific drugs in plasma. Tandem mass spectrometry (LC-MS/MS) further enhances structural elucidation by fragmenting precursor ions and analyzing their product ion spectra, providing detailed information on molecular structures, functional groups, and fragmentation pathways.
- Overall, LC-MS is valued for its sensitivity, selectivity, and ability to handle complex biological and environmental samples with minimal sample preparation. Its broad applicability, coupled with ongoing advances in instrumentation and bioinformatics, makes it an indispensable tool in modern analytical science.
