Advances in Ultra-High-Resolution Mass Spectrometry for Pharmaceutical Analysis

Abstract

Pharmaceutical analysis refers to an area of analytical chemistry that deals with active compounds either by themselves (drug substance) or when formulated with excipients (drug product). In a less simplistic way, it can be defined as a complex science involving various disciplines, e.g., drug development, pharmacokinetics, drug metabolism, tissue distribution studies, and environmental contamination analyses. As such, the pharmaceutical analysis covers drug development to its impact on health and the environment. Moreover, due to the need for safe and effective medications, the pharmaceutical industry is one of the most heavily regulated sectors of the global economy. For this reason, powerful analytical instrumentation and efficient methods are required. In the last decades, mass spectrometry has been increasingly used in pharmaceutical analysis both for research aims and routine quality controls. Among different instrumental setups, ultra-high-resolution mass spectrometry with Fourier transform instruments, i.e., Fourier transform ion cyclotron resonance (FTICR) and Orbitrap, gives access to valuable molecular information for pharmaceutical analysis. In fact, thanks to their high resolving power, mass accuracy, and dynamic range, reliable molecular formula assignments or trace analysis in complex mixtures can be obtained. This review summarizes the principles of the two main types of Fourier transform mass spectrometers, and it highlights applications, developments, and future perspectives in pharmaceutical analysis.

Identification of Acid Hydrolysis Metabolites of the Pimelea Toxin Simplexin for Targeted UPLC-MS/MS Analysis

“…The current method on the Orbitrap showed simplexin LOD to be five times more sensitive when compared to the older triple quadrupole used in Fletcher et al [ 9 ]. The high resolving power and mass accuracy of the Orbitrap [ 31 , 32 ] allowed simplexin analysis in very low concentrations and allows the identification of potential simplexin metabolites.…”

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

“…HRMS such as Orbitrap or Fourier transform ion cyclotron resonance provided excellent mass accuracy, acceptable dynamic range, reliable assignments of molecular formulas, and the ability to analyze trace compounds in complex mixtures [ 17 ]. Therefore, LC-HRMS could be utilized to conduct untargeted analyzes of anti-TB drugs and endogenous metabolites simultaneously.…”

“…Regardless of the type of biospecimens, it includes high sensitivity and selectivity, broad linear ranges, high-throughput capability, and simultaneous analysis (measurement of both parental and active metabolites or multiple co-medications) [ 16 ]. Furthermore, the possibility of dissociating ion(s) into fragments and detecting the mass-to-charge ratio ( m/z ) of the ion(s) by using LC-tandem mass spectrometry (LC-MS/MS) enhances the selectivity [ 16 , 17 ]. Many LC-MS/MS methods have been established to measure concentrations of anti-TB agents and their metabolites in various matrices [ [18] , [19] , [20] , [21] , [22] ].…”

“…Many LC-MS/MS methods have been established to measure concentrations of anti-TB agents and their metabolites in various matrices [ [18] , [19] , [20] , [21] , [22] ]. Therefore, it has arguably become the gold standard in research and applications on small molecule analysis, either of exogenous or endogenous origins [ 17 , 23 ]. LC-MS is a powerful technique for drug quantification and multi-omics analyses, including proteomics and metabolomics.…”

The Crosstalk between Gut Microbiota and Nervous System: A Bidirectional Interaction between Microorganisms and Metabolome

“…However, a significant number of compounds in complex mixtures give variable responses during MS, making the interpretation of results difficult; in addition, MS often leads to the degradation of analytes, or the disruption of their molecular complex interactions, ultimately leading to the loss of important information. Finally, MS-based metabolomics analyses are disadvantaged in terms of repeatability, inter-evaluator fidelity, and reproducibility, and thus require the use of complex statistical tools for processing the results [ 18 ].…”