Multi-Target Screening of Biological Samples Using LC–MS/MS: Focus on Chromatographic Innovations

Abstract

Multi-target screening of biological fluids is a key tool in clinical and forensic toxicology. A complete toxicological analysis encompasses the sample preparation, the chromatographic separation and the detection. The present review briefly covers the new trends in sample preparation and detection and mainly focuses on the chromatographic stage, since a lot of technical improvements have been proposed over the last years. Among them, columns packed with sub-2 μm fully porous particles and sub-3 μm core-shell particles allow for significant improvements of resolution and higher throughput. Even if reversed-phase LC remains the most widely used chromatographic mode for toxicological screening, hydrophilic interaction chromatography and supercritical fluid chromatography appear as promising alternatives for attaining orthogonal selectivity, retention of polar compounds, and enhanced MS sensitivity.

SFC–MS Versus RPLC–MS for Drug Analysis in Biological Samples

“…With such a mobile phase, and considering the wide range of stationary phase chemistries available for SFC operation (e.g., polar, nonpolar, aromatic and mixedmode), this separation technique covers the application domain of different chromatographic modes including normal-phase LC, reversed phase LC (RPLC) and hydrophilic (2015) 7(10) future science group Editorial Desfontaine, Nováková & Guillarme interaction chromatography. As described in [6], the range of analytes compatible with SFC is very broad since compounds possessing log P between -2 and >10 were successfully analyzed.…”

“…When dealing with the analysis of biological samples, another important aspect to consider is compatibility of the separation technique with MS, as this detector allows improving selectivity, sensitivity and identification power [6]. In theory, the coupling of SFC with ESI source should be straightforward since the mobile phase is composed of a high proportion of CO 2 , which should enhance the evaporation step during the ionization process.…”

“…These new systems tackle the above-mentioned shortcomings. In addition, they also make SFC compatible with the most recent column types, such as the ones packed with fully porous sub-2 μm particles, or with sub-3 μm superficially porous particles [5].When dealing with the analysis of biological samples, another important aspect to consider is compatibility of the separation technique with MS, as this detector allows improving selectivity, sensitivity and identification power [6]. In theory, the coupling of SFC with ESI source should be straightforward since the mobile phase is composed of a high proportion of CO 2 , which should enhance the evaporation step during the ionization process.…”

Systematic evaluation of matrix effects in hydrophilic interaction chromatography versus reversed phase liquid chromatography coupled to mass spectrometry

“…ACN or MeOH with a 3:1 (v/v) ratio is considered one of the most efficient PP procedure for such biosamples [39], but it cannot be used prior to SPE since an immediate elution of the compounds would occur during sample loading. Thus, a solution of 6% perchloric acid was used for PP prior to SPE procedure [39]. It may have led to a less efficient removal of other endogenous interferents than ACN [36].…”

“…The targeted compounds were not eluted at the beginning or the end of the chromatogram, which corresponded to the range where the most important signal modifications occurred in RPLC mode [1,5,7,34]. ACN or MeOH with a 3:1 (v/v) ratio is considered one of the most efficient PP procedure for such biosamples [39], but it cannot be used prior to SPE since an immediate elution of the compounds would occur during sample loading. Thus, a solution of 6% perchloric acid was used for PP prior to SPE procedure [39].…”