Recent applications of liquid chromatography tandem mass spectrometry at various stages of drug development
摘要
Liquid chromatography–tandem mass spectrometry is a combination of liquid chromatography and mass spectrometry. In this process, high-performance liquid chromatography separates analytes, ionizes them, and then analyzes them using mass filters that are based on mass-to-charge ratio. The strength of the signal shows the concentration. It surpasses traditional high-performance liquid chromatography and immunoassays in sensitivity, specificity, and multi-analyte capabilities, offering better throughput than gas chromatography–mass spectrometry while accommodating higher molecular weight or highly polar molecules. Liquid chromatography–tandem mass spectrometry is widely used in therapeutic drug monitoring, endocrinology, and toxicology.
Main textThis article outlines the advantages and pharmaceutical applications of LC–MS/MS in quantifying various drugs, metabolites, and genotoxic impurities. It is also used in therapeutic drug monitoring and proteomics. This technique allows for precise quantification of compounds, including antidepressants, antipsychotics, benzodiazepines, antifungals, and antihypertensives across diverse biological matrices. Therapeutic drug monitoring benefits from LC–MS/MS by accurately measuring drug levels to optimize dosage for drugs with narrow therapeutic ranges, like immunosuppressant and anticancer drugs. It also quantifies genotoxic impurities, such as sulfonate esters and nitrosamine impurities, in drug substances. LC–MS/MS is also used in stability-indicating methods for various drugs and for the quantification of drugs in dosage forms. Excellent sensitivity and specificity within protein analysis in proteomics are achievable with LC–MS/MS. Thousands of proteins can be precisely measured through methods like parallel reaction monitoring and selected reaction monitoring.
ConclusionLC–MS/MS is a fast and accurate way to measure different drugs, metabolites, and genotoxic impurities in pharmaceutical analysis. It is also used in stability-indicating methods and for the quantification of drugs in dosage forms. Compared to high-performance liquid chromatography with ultraviolet detection, radioimmunoassay, enzyme-linked immunosorbent assay, and gas chromatography–mass spectrometry, liquid chromatography–tandem mass spectrometry is a powerful analytical method that offers quick, precise analysis and improved selectivity and sensitivity.