**Author details**

*Mass Spectrometry - Future Perceptions and Applications*

nents cause ion suppression are as follows:

insufficient desolvation [121, 124].

and become better acquiescent to automation.

• Gas phase deprotonation.

surface.

higher dilution [128].

**5. Conclusion**

unrelated to the analyte" [105, 106]. The process of ion suppression/enhancement is in general referred as matrix effect and is main subject of various published reviews [107–112].Matrix effects result in significant deviation in precision and accuracy of results which in turn debate the reliability of pharmacokinetic parameters of NCE's generated. Matrix effect alters the sensitivity, reproducibility and challenges the reliability of analytical techniques. Although matrix effects occur as a result of various exogenous and endogenous components, one major area of concern is formulation excipients (an exogenous component) used in the preparation of formulations. Dosing vehicles are generally used at high concentrations to solubilize test articles of highly lipophilic nature [113–115]. This in turn can be instrumental in causing matrix effects, thereby questioning the reliability of preclinical PK parameters. This phenomenon has been reported by us in the past for various excipients such as PEG

400 [110, 116, 117], Cremophor EL [111, 118] and Solutol HS15 [112, 119].

Several mechanisms have been proposed to explain matrix effects, but the exact process remains uncertain [120, 121]. Various mechanisms by which matrix compo-

• Change in droplet surface tension leading to formation of large droplets and

• Preferential ion evaporation due to matrix components gathering at droplet

Reduction of matrix effects can be achieved through various strategies includ-

Over the past few decades, technological advancements in mass spectrometer enabled it to surpass other detection platforms and evolve as an indispensable analytical tool to support the bioanalytical needs of drug discovery and development. Current generation mass spectrometers could efficiently handle both qualitative and quantitative aspects of bioanalysis. Additionally, the likelihood of hyphenation of mass spectrometers with ultrafast liquid chromatography systems, extended its applications to high throughput bioanalysis. Even though significant achievements were made in the past, instruments will continue to get more and more sensitive

• Charge competition between analyte and matrix components [122, 123].

• Change in mass of analyte ion due to ion pairing and adduct formation

ing decreasing the level of matrix components, improving chromatographic separation of interfering materials from the analyte, various sample preparation strategies, lower injection volumes, and even by simple dilution of samples to reduce the overall concentrations of both analyte and co-extracted materials [126, 127]. Switching ionization sources will also help in mitigating the matrix effects [112, 116, 118, 119]. Matrix effects occurring in the early time point samples can be monitored, using another aliquot of the early time point samples analyzed at a

• Co-precipitation with non-volatile matrix components [125].

**56**

Vijayabhaskar Veeravalli1 \*, Lakshmi Mohan Vamsi Madgula1 and Pratima Srivastava<sup>2</sup>

1 Syngene International Limited, Biocon Park, SEZ, Bangalore India

2 GVK BIO Pvt Ltd, Hyderabad, Telangana, India

\*Address all correspondence to: vveerav1@jhmi.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
