Know The Basics: Pros And Cons of LC-MS Method Development And LCMS Testing

LC-MS systems combine liquid chromatography and mass spectrometry to identify and quantify compounds in complex study samples. Irrespective of the drug discovery vs. drug development debate, scientists employ LC-MS systems throughout the drug development life cycle. However, with any technique, LC-MS has its strengths and weaknesses. The current article highlights them for the readers.

Pros of LC-MS testing and LC-MS method development

The primary strength of LC-MS analysis is that they fulfill all limitations of traditional immunoassays. Following is a comprehensive list of lc ms method development .

Selectivity

High-resolution separation is a characteristic feature of the LC-MS method. LC-MS analysis can identify and quantitate biomolecules in complex biological matrices. They can even distinguish biomolecules that are structurally very similar. Though LC-MS can face issues due to interference, researchers easily fix them by modifying MS conditions. A novel LC-MS assay can be developed within days, which takes several months for traditional immunoassays. 

Sensitivity

Sophisticated MS units can detect at attomole levels. However, to achieve this level of sensitivity, researchers must thoroughly focus on sample preparation and chromatography development.

Sample throughput

Ultra high-performance liquid chromatography can achieve a separation time of fewer than five minutes. Both analyses by MS and separation by LC component take place concurrently. Hence, no additional time is required. Automated systems need no human handling. However, researchers must run each sample in a sequence.

Sample volumes

LC-MS typically requires less than 5 µl of sample volume. Hence, researchers can micro-sample the assay and save valuable samples or samples that are available in smaller quantities, such as CSF.

Cost per sample

Most LC components are relatively less expensive. Besides, a typical LC column provides over 500 separations with low sample volumes.

Reproducible

LC-MS assays have higher inter and intra-assay reproducibility. Moreover, retention times are exceptionally high, and recent advances in ionization have greatly enhanced the measurement reproducibility of MS units.

Multiplexing

Multiplexing is one of the most vital advantages of LC-MS systems. Besides, compared to immunoassays, LC-MS systems require no extra costs or time to assess additional target analytes.

Extended compound range

LC-MS testing is not just restricted to biomolecules. As long as a molecule is ionizable, LC-MS can quantity all inorganic or organic compounds. Though LC-MS is widely used in quantifying and detecting biomolecules, they are increasingly becoming specialized in therapeutic drug monitoring.

Cons of LC-MS method development and LC-MS analysis

LC-MS has many advantages over traditional immunoassays. However, immunoassays are still widely used in bioanalytical studies, which means LC-MS has its limitations.

Equipment costs

A vast installation cost is a primary reason why smaller laboratories do not readily adopt LC-MS. Moreover, the equipment cost rises with more specialized MS detectors. However, the cost per analysis does come down when operating LC-MS systems over several years.

Equipment complexity

MS units are complex. Assessing MS spectra is also challenging to interpret. Hence, LC-MS analysis requires skilled staff trained in operating LC-MS systems. Although, current automated systems and software have considerably reduced LC-MS assay complexity.

Sample complexity

Clinical samples are inherently complex. To assess analytes present at lower concentrations, scientists first remove proteins that are present in abundance. This step increases the sample complexity while running LC-MS systems.

LC-MS is a robust bioanalytical method validation . However, researchers must focus on LC-MS validation to ensure reliable and accurate results.