Qualitative and quantitative mass spectrometry imaging of drugs and metabolites

Abstract

Mass spectrometric imaging (MSI) has rapidly increased its presence in the pharmaceutical sciences. While quantitative whole-body autoradiography and microautoradiography are the traditional techniques for molecular imaging of drug delivery and metabolism, MSI provides advantageous specificity that can distinguish the parent drug from metabolites and modified endogenous molecules. This review begins with the fundamentals of MSI sample preparation/ionization, and then moves on to both qualitative and quantitative applications with special emphasis on drug discovery and delivery. Cutting-edge investigations on sub-cellular imaging and endogenous signaling peptides are also highlighted, followed by perspectives on emerging technology and the path for MSI to become a routine analysis technique.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 1: Surface and Cross-Sectional Chemical Analysis

“…For ions with an equal charge, this 6 will result in equal kinetic energy and thus the velocity of these ions will depend on their massto-charge ratio (m/z). Hence, the time needed to reach the detector is indicative for the m/z of the detected molecular fragment and will result in a negative or positive mass spectrum, depending on the charge of the collected molecular fragments 19,20,[25][26][27] ToF-SIMS has a very low detection limit (ppb range), a high surface sensitivity and high spatial resolution (0.2µm) 28 . Owing to these properties, ToF-SIMS is highly suited for surface chemical identification and surface chemical distribution (mapping) and will therefore be used to analyze the layered beads, and by doing so, elucidate their chemical structure.…”

Recent Advances in Solid-State Analysis of Pharmaceuticals

“…In the last decade or so, mass spectrometry imaging (MSI) has garnered considerable interest in the pharmaceutical community [21]. It detects the actual molecules in the image based on their characteristic mass-to-charge ratios (m/z) and does not require the use of labelled compounds such as those used in chemical imaging.…”

“…The three most common sources for MSI: (a) Desorption electrospray ionization which uses a stream of solvent ions to desorb and ionize analyte molecules, (b) secondary ion mass spectrometry which uses a beam of ions from an ion gun to sputter analyte ions off the sample, and (c) matrix-assisted laser desorption/ ionization which uses laser irradiation of a matrix-coated sample for desorption and ionization. "Reprinted (adapted) with permission from [21]. Copyright (2015) Elsevier."…”

“…In addition to that, depth profiling can offer very sensitive compositional and molecular information as a function of depth as well as provide full 3-dimensional distributions within the analysed volume [22,23]. Time-of-flight instruments have resolving powers ranging from 10,000 to 100,000 and can routinely achieve less than 5 ppm mass accuracy [21]. Moreover, using tandem mass spectrometry (MS/MS) will increase confidence in drug identification and improve the dynamic range of the analysis.…”

“…Thus by measuring the time it takes for the secondary ions to reach the detector, the mass-to-charge ratio can be deduced and used to separate them. A diagram depicting the process of ionization is given below [21].…”