Utility of Mass Spectrometry for Pharmaceutical Profiling Applications

Abstract

MS has great utility for pharmaceutical profiling, the measurement of physicochemical and metabolic properties that are crucial to the discovery and development of new drug candidates. An evaluation of the capabilities of MS to improve the speed, specificity, sensitivity and cost per compound of method in development indicates when MS technologies have utility compared to other analytical techniques. MS has been used successfully for methods that profile the critical properties: permeability, lipophilicity, plasma and solution stability, solubility, plasma protein binding and integrity. In general, MS has utility in these methods using analytical strategies involving unique MS technologies (e.g., parallel multiplexed interfaces, trap-and-elute), orthogonal detection to UV, high sensitivity for low LOQs, low concentration studies, highly specific MS/MS SRM, combinatorial analysis, use of internal standards, providing initial structural data in addition to quantitative and facile integration with HPLC autosamplers and other hardware that allow enhanced on-line experiments. Ultimately, it is important to evaluate the appropriateness of any technique that is being considered for use in a method, to insure that it best meets all of the criteria for the organization's needs.

Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry: Application to a pharmacokinetic study

“…The combination liquid chromatography/mass spectrometry is currently accepted as being a powerful means of determining organic molecules from complex biological matrices [21][22][23]. The selectivity and sensitivity of LC-MS/MS allowed analysis times to be reduced, such that sample preparation time often exceeds the analysis time of samples.…”

MS Applications in Support of Medicinal Chemistry Sciences

“…one solution is to use liquid chromatography with well-end-capped C 18 type of stationary phase allowing a rather good correlation between the retention time index (logk) and logP to be made, the general setup being the calculation of the logP by comparing the retention time of the test compounds with the retention time of well-known standards. A variety of semi-quantitative isocratic and even faster gradient methods using different commercially available HPlC columns, and ultimately the new uPlC technique, coupled to both MS and MS/MS detection, have been reported and are based on using very small amounts of the compound [101,108,111]. An interesting HPlC-MS-based method able to simultaneously assess the lipophilic in terms of the logD and the purity/compound integrity was described in 2003 by Kerns et al [110].…”

Ultra-high capacity liquid chromatography chip/quadrupole time-of-flight mass spectrometry for pharmaceutical analysis

“…The quantitative analysis of active pharmaceutical ingredients (API) including their related impurities and degradation products is one of the most active areas in modern analytical chemistry [1][2][3][4]. The purity profiling for API in any pharmaceutical product is crucial to ensure the quality of the drug while API quantitation in preclinical and clinical samples plays an important role in drug discovery and development.…”