Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

Abstract

Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

Small molecule-sensing strategy and techniques for understanding the functionality of green tea

“…5) To overcome the limitation of the 1,5-DAN-MALDI-MSI technique and to ensure its practical use, further improvement of its detection sensitivity, such as employing a targeted selective reaction monitoring mode (SRM) approach using a triple quadrupole system (QqQ), 89) application of a Fourier transform ion cyclotron resonance-MS (FT-ICR-MS) instrument capable of accumulating continuously selected ions, 90) and on-tissue chemical derivatization approaches to increase the ionization efficiency 91,92) as well as the improvement of MALDI efficiency based on matrix choice and development, may be required. Additionally, other studies including kinetic histochemistry, 80,84,93) microscopic analysis with high-spatial resolution, [94][95][96] 3D imaging, [97][98][99] , and distribution of other metabolites 86,99) will be required to unravel both the biological consequences of biotransformation of the dietary polyphenol and its mechanism (s) of action.…”

MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications

“…Other groups increased the ionization of the target molecule by adapting the matrix composition (Atkinson et al 2007) or the application procedure (Goodwin et al 2010b). Chemical derivatization may be employed to increase ion yields (Manier et al 2011). This approach may be also useful if the target molecules are within the low-molecular weight region (less than m/z 1,000), since there is a strong chemical background in this mass range, created by ions from compounds endogenous to the tissue sample, such as matrix clusters or lipids .…”

“…Some studies addressed this issue by spotting a dilution series of the compound of interest directly on the tissue sections or carrier to obtain a linear standard curve (Hsieh et al 2006;Nilsson et al 2010), but most combined liquid chromatography coupled with MS/ MS for the quantification and confirmation of molecular species in tissue sections (Goodwin et al 2010b;Manier et al 2011;Prideaux et al 2011;Reyzer et al 2003;Signor et al 2007). However, quantification of MALDI-IMS data is still an ongoing technical challenge, due to the lack of appropriate calibration and internal standards, but novel approaches have been proposed (Koeniger et al 2011).…”

“…Despite these current challenges, MALDI-IMS has so far been successfully applied in several studies for analyzing pharmaceutical compounds in cancer (Atkinson et al 2007;Bouslimani et al 2010;Marko-Varga et al 2011;Signor et al 2007;Trim et al 2008), lung diseases (Manier et al 2011;Nilsson et al 2010;Prideaux et al 2011), and brain diseases (Hsieh et al 2006;KhatibShahidi et al 2006;Koeniger et al 2011). Bouslimani et al (2010) observed by MALDI-IMS that oxaliplatin and its metabolites showed an almost exclusive presence at the margins of rat kidneys, whereas the previously applied heat treatment was expected to increase the uptake of the drug into the kidney.…”

A derivatization and validation strategy for determining the spatial localization of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry

“…However, the selection of the optimal MALDI matrix [20][21][22] or chemical derivatization of the analytes [18,[23][24] in tissue may be used to minimize molecular interferences and improve sensitivity. The use of high-resolution FT-MS analysis [12,25] or MS/MS analysis [7,[10][11] may aid in the detection of some compounds when simple sample preparation procedures alone are insufficient.…”