Quadrupole mass spectrometry molecules

Currently, high-performance liquid chromatography (HPLC) combined with atmospheric pressure ionization (API) triple-quadrupole mass spectrometry (MS) is the predominate quantitative technique used in modem pharmaceutical bioanalysis. The key technological achievement in API-MS was the efficient ionization in a liquid stream and transference of ions from atmosphere to vacuum. Of the API approaches developed, electrospray ionization (ESI) is the most commonly used. ESI provides an efficient means of soft ionization amenable to most molecules encountered in a dmg discovery setting. An alternative soft ionization approach is the use of desorption ionization (DI) techniques. The major distinguishing feature of DI techniques is that ions are typically produced from dried samples. 

The vapour pressures of all lanthanide trifluorides have been measured, including P111F3. Various techniques have been used, which can be divided in indirect techniques (effusion and boiling point methods) which provide accurate data for the total vapour pressure, and direct mass spectrometric techniques, which are less precise, particularly in case of quadrupole mass spectrometry, but give information on the vapour composition and the presence of dimeric or polymeric molecules or dissociation products. 

Rathore R, Coir JJ, Lebre DT, Seibel WL, Greis KD (2009) Extending matrix-assisted laser desorption/ionization triple quadrupole mass spectrometry enzyme screening assays to targets with small molecule substrates. Rapid Commun Mass Spectrom 23 3293-3300... 

MALDl coupled with triple quadrupole mass spectrometry has been shown recently to be a potentially ultra-high-throughput technique for small molecule quantification. MALDl analyses can be achieved in 1 s per sample with adequate sensitivity, accuracy and precision for in vitro ADME quantification, as presented at the 55th ASMS Conference on Mass Spectrometry and Allied Topics. For quantitation by MALDl, microsomal incubations are performed and the reactions quenched by acetonitrile precipitation. Immediately afterwards, the samples are applied to 96- or 384-well SPE clean-up and the eluate applied to the MALDl target. Figure 21.10 shows an example of microsomal stability analysis by the... 

Tandem mass spectrometry (MS/MS) is a method for obtaining sequence and structural information by measurement of the mass-to-charge ratios of ionized molecules before and after dissociation reactions within a mass spectrometer which consists essentially of two mass spectrometers in tandem. In the first step, precursor ions are selected for further fragmentation by energy impact and interaction with a collision gas. The generated product ions can be analyzed by a second scan step. MS/MS measurements of peptides can be performed using electrospray or matrix-assisted laser desorption/ionization in combination with triple quadruple, ion trap, quadrupole-TOF (time-of-flight), TOF-TOF or ion cyclotron resonance MS. Tandem... 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Kovarik, P., Corr, J. J., and Covey, T. R. (2003). Application of orthogonal MALDI for quantitation of small molecules using a triple quadrupole mass spectrometer. In Proceedings of The 51st ASMS Conference on Mass Spectrometry and Allied Topics, Montreal, Canada. 

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