The primary drug discovery technique is to identify or find out new drug candidates with the assistance of screening chemical libraries of small molecules, natural extracts instead of biological targets. At the same time, screening is done for compounds with therapeutic effects. Medicinal chemistry plays a pivotal role in ensuring that the chemical libraries are a fir-for-purpose to a broad range of disease targets and evolving molecules for drug candidates. The inclusion of proteomics, parallel chemistry, absorption, distribution, metabolism, and excretion (ADMET) plays a crucial role in the new leads.
The Evolved techniques such as LC-MS/MS analysis plays a pivotal role in a series of phases of the drug discovery process to identify and analyze compounds. The LC-MS method assesses a particular drug candidate for efficacy, adsorption, desorption, metabolism, elimination, and toxicity; quality control characterization, biological screening, physical properties, and DMPK properties is a must. The techniques are tedious, too expensive, and challenging, and consists of screening to obtain optimized compound properties.
Mass Spectrometry is a productive tool for high-quality compound libraries, to evaluate compound properties, and to reduce the time required for the process. MS is apt in the development of qualitative and quantitative analytical methods meant for drug discovery. LC-MS testing in combination is highly efficient in the separation of complex mixtures using multi-dimensional LC (2DLC) and other sensitive, much higher resolution and ion mobility separations by MS.
Two-dimensional LC-MS analysis or LC-MS assay are highly efficient techniques in analyzing and characterizing complex samples like active pharmaceutical ingredients (APIs) in the separation of compounds of interest (COI) along with LC in the determination of COI purities, identities, and structures by UV diode array detection (DAD) and MS. In recent times, online two-dimensional HPLC (2DLC) is getting commercial and is opted by the pharmaceutical industry.2DLC enhances the peak capacity and resolves power, and can resolve complex mixtures that were initially not feasible by one dimensional HPLC.
According to reports, 2DLC applies to many needs such as sample analysis in complex matrices, enhanced profiling of complex mixtures, compound degradation studies, quantification of impurities that are a part of co-elute, and API separations of the chiral compound. A combination of 2DLC with a mass spectrometer (2DLC-MS) is potent for identifying trace-level impurity and quantification while minimizing the buffer and matrix interference to obtain enhanced MS sensitivity.
High-resolution MS for quantitative analysis/MS-based quantitative analysis has conventionally been established using tandem mass spectrometer ( LC MS ). This method is stable and is contemplated as the ‘highest standard’ for MS quantification for its extreme selectivity and sensitivity. This method’s procedure is quite tedious and time-consuming as it comprises several operations of product selection, parent-ion fragmentation, and collision energy optimization. In the recent era, the researchers have put forward details regarding the usage of high-resolution accurate mass (HRMS) systems for quantitative analysis, which is extremely simple and is independent of fragmentation for quantitative analysis.
However, the latest advancements seem to have many advances not just with instrumentation and ionization technology, but it is also seen in separation science like multi-dimensional LC-MS method that employs separation and analysis for dealing with complex problems. The evolvements in mass spectrometers and separation science will enhance the potential and application of LC-MS method development in all facets of research.