The liquid chromatography-mass spectrometry (LC-MS) technique is a powerful tool for identifying and quantifying analytes in complex biological matrices. It requires low sample volumes and provides sensitivity, selectivity, and speedy results, making it an ideal tool for drug discovery and development studies.
The liquid chromatography segment separates the target analyte from the mixture, while the mass spectrometer unit measures the analytes based on their mass-to-charge ratio. Several innovative approaches are constructed to connect the LC and MS components. The current article focuses on concerns for LC-MS assays during drug discovery and development studies. This article highlights considerations for each stage of drug development. However, LC-MS method development remains a crucial aspect of reliable drug development studies.
LC-MS analysis in the drug discovery process
Early DMPK analyses are crucial for the success of new drug entities in completing the drug development process. Today LC-MS/MS systems with API and SRM modes have become the primary quantitative technique for drug discovery studies.
In vitro studies is one of the earliest screening approaches employed to study reduction, oxidation, and glucuronide conjugation in several animal models. Often, drug compounds produce metabolites with complex rearrangements. However, newer LC-MS/MS techniques help identify metabolites even at femtomole levels. The LC component efficiently separates the drug compound, whereas the MS unit accurately identifies individual constituents. Besides, the development of tandem mass spectrometers has further enhanced the sensitivity of LC-MS systems. Moreover, LC-MS systems can analyze multiple chemicals simultaneously, reducing assay run times and improving experimental throughput.
LC-MS in preclinical studies
Researchers employ in vitro and in vivo approaches to study the safety and efficacy of a drug product during the preclinical drug development phase. Several bioanalytical assays are used to evaluate the absorption and elimination of the drug in a study model. Also, approaches like tissue distribution and toxicokinetic studies analyze drug movement through various body compartments.
Over time, LC-MS systems have increasingly been used to identify degradants, impurities, and metabolites in preclinical studies. In addition, developing hyphenated techniques such as LC-MS/MS assays has further upgraded their use in drug development studies. Nevertheless, LC-MS/MS method development and validation will be necessary to ensure the reliability of the generated study results.
LC-MS in clinical studies
MS systems have developed significantly through research and routine analysis. Approaches such as ESI-LC-MS/MS systems and MALDI ionization have made LC-MS analysis an integral technique for studies used in clinical trials. Moreover, LC-MS/MS systems are currently widely used to generate clinical data. The principal consideration for using LC-MS systems in clinical studies is utilizing multidimensional LC-MS procedures. ls.
Conclusion
LC-MS analysis is a robust technique for screening and testing newer therapeutics and pharmaceutical interventions. Besides, it is a powerful tool for identifying, quantifying, and understanding the structural complexity of drugs, proteins, and biomarkers. However, they are associated with challenges such as high cost, specialized skilled staff, and complex operations. Not to mention, adequate approaches in LC-MS method development are necessary for its sustained use in clinical laboratories.
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