7 Vital Roles & Application of LC-MS In Preclinical Trials
The LC-MS method has become the primary choice of bioanalytical technique in the drug development process. The objective of the drug development process is to identify lead molecules that have the potential to emerge as a drug compound against disease and medical conditions. Researchers use LC-MS and LC-MS/MS assays throughout the drug development process. In the initial stages, LC-MS checks the purity and synthesis of lead compounds. In the second stage, researchers employ LC-MS to understand the chemical properties of the drug products. In later stages, crucial drug metabolism and pharmacokinetics tests are also performed using LC-MS and LC-MS/MS analysis. Hence, LC-MS assays have widespread applications in the development of drug products. The current article focuses on preclinical drug development and presents seven vital roles and applications of LC-MS in preclinical trials.
LC-MS systems are generally used in building a compound library of new drug entities. LCMS method provides information on the identity and purity of a drug entity and sorts them for compound libraries. Generally, a UV system assesses compound purity, and the MS unit confirms the identity. Besides, the MS unit used can be a single quadrupole or TOF system.
Although studies employ fluorescence techniques for high-throughput screening of drug compounds, researchers have also used LC-MS analysis for screening compounds. LC-MS uses a target protein plus compound mixtures to identify potential drug compounds. The LC-MS system identifies the ligand compounds using the TOF-MS system.
LC-MS method is most widely used to assess the ADME-PK properties of a drug product. Most ADME-PK properties provide a powerful understanding of drug metabolism and pharmacokinetics. There are several in vitro ADME assessments followed by in vivo preclinical evaluations. Most of these studies are supported by LC-MS analysis.
In vitro screening
In vitro testing is most commonly done by using three screening tests. Each screening tests a particular feature or ability of the drug compound. The human colon adenocarcinoma cell line measures the permeability of a drug compound. Another in vitro assay evaluates the potential of inhibiting human cytochrome p450 isoforms. This test is crucial in understanding drug-drug interactions. The third test is the metabolic stability assay. This assay aims at understanding the in vivo intrinsic clearance of a drug compound. All these screening tests employ the LC-MS method for robust analysis.
In vivo PK screening
LC-MS systems are widely used to assess in vivo PK screening of drug compounds, with triple quadrupole mass spectrometers being employed the most. In vivo screening provides a relatively lower throughput compared to in vitro assays. However, researchers primarily focus on sample preparation strategies, a faster HPLC system, and sample reduction options to increase in vivo PK screening the throughput.
LC-MS has emerged as an exceptional tool for identifying metabolites. Although a triple quadrupole mass spectrometer is sufficient for metabolite identification, it is recommended to use additional types of MS units.
As LC-MS becomes faster, matric ion suppression or matrix effects are a prominent concern. Matric effects can either reduce or enhance the response. Researchers can use the post-column infusion technique to lower the matrix effect. However, with time and experience, investigators can efficiently deal with potential matrix issues.
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