Fast Mass Spectrometry-Based Methodologies for Pharmaceutical Analyses

Abstract

Historically, most bioanalytical methods for drug analysis in pharmaceutical industry were developed using HPLC coupled with UV or fluorescence detection. However, there is a trend toward interfacing separation technologies with more sensitive tandem mass spectrometry (MS/MS)-based systems. MS/MS detection offers complete resolution of the parent compounds from their first pass metabolites to avoid extra efforts for separation and sample clean-up procedures resulting in shorter run times. With the increasing demand for ever faster screening, there is a continuing demand for bioanalytical methods possessing higher sample throughput for both in vitro and in vivo drug metabolism and pharmacokinetic evaluations to accelerate the discovery process. This review focuses on the current approaches for fast MS-based assays (cycle-time less than 5 min) of pharmaceuticals and their metabolites that have been reported in the peer-reviewed publications.

A mixed-mode liquid chromatography-tandem mass spectrometric method for the determination of cytarabine in mouse plasma

“…The high performance liquid chromatography (HPLC) coupled with a tandem mass spectrometer (MS/MS) provides excellent sensitivity and selectivity for monitoring drug compounds and has become a standard equipment in modern pharmaceutical industries [4,5]. While fast liquid chromatography technologies using a micro-column [6,7], monolithic silica column [8,9] or ultra-performance [10,11] linked with a tandem mass spectrometer have been utilized to shorten run cycle times, it is important to maintain appropriate separation power to avoid ion suppression issues or endogenous interferences [6,7,12].…”

Supercritical fluid chromatography‐mass spectrometry for chemical analysis

“…Addition of a proton-donating organic modifier such as methanol to the CO 2 generation. For the APCI, the effluent is vaporized through the heated nebulizer which consists of a pneumatic nebulizer and a heated quartz tube.…”

The Role of Liquid Chromatography–Mass Spectrometry in Pharmacokinetics and Drug Metabolism

“…Toward this end, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo-ionization (APPI) have proven valuable for both qualitative and quantitative screening of small molecules (e.g., pharmaceutical products) [9][10][11][12][13][14].…”