Combining MALDI mass spectrometry imaging and droplet-base surface sampling analysis for tissue distribution, metabolite profiling, and relative quantification of cyclic peptide melanotan II

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

“…Melanotan II is a cyclic heptapeptide drug that has been shown to increase insulin sensitivity, increase skin pigmentation, and treat sexual dysfunction in various preclinical and clinical studies 63 . Of particular interest, Chen et al .…”

“…used both matrix‐assisted laser desorption/ionization (MALDI)‐FT‐ICR‐mass spectrometry imaging (MSI) to study the spatial distribution of the drug and its metabolites in resected organs and whole‐body tissue, and droplet‐based liquid micro‐junction surface sampling‐HPLC‐Q‐Orbitrap‐MS to provide a chromatographic separation, molecular profiling, structural elucidation, and quantification of tissue analytes at the expense of spatial resolution. This work highlights the capabilities of using these label‐free MS techniques, either together or independently, to qualitatively study the pharmacokinetics and pharmacodynamics of a drug to evaluate in vivo stability and biodistribution 63 . However, the lack of chromatographic separation and the influence of matrix effects makes it unlikely that MSI will become a widely used quantitative technique for small molecules in biological matrices.…”

“…62 Melanotan II is a cyclic heptapeptide drug that has been shown to increase insulin sensitivity, increase skin pigmentation, and treat sexual dysfunction in various preclinical and clinical studies. 63 together with network protein analysis to identify and quantify the proteome's changes. Overall, 2328 proteins were identified of which 39 altered significantly in 0.125% LWM-HA, 149 in 0.25% LWM-HA, and 496 in 0.50% LWM-HA.…”

Toward Revealing Microcystin Distribution in Mouse Liver Tissue Using MALDI-MS Imaging

“…Here, matrix-assisted laser desorption/ionization MS imaging (MALDI-MSI) was investigated as a method that could provide information about MC localization and distribution in the mouse liver. MALDI-MSI is a label-free technique that has been used to simultaneously image different molecules, including cyclic peptides, in tissue sections with high sensitivity and near-single-cell resolution [19,20]. The technique allowed studying the distribution of molecules in tissue sections covered with an organic matrix, which absorbs the light from a pulsed laser and supports efficient ionization of peptides and other biomolecules.…”

Local metabolism in preclinical disease models studied with mass spectrometry imaging

“…Most of targeted MALDI-MSI metabolomics studies focus on the local detection of drugs, toxicants and their metabolites in different tissues to investigate their pharmacological/toxicological effects [188]. These exogenous compounds include acetaminophen [189], cyclic peptide melanotan II [190], scutellarin [191], thymoquinone [192], sulfamethoxazole [193], triamcinolone acetonide [194], sunitinib (anti-angiogenic drug) [195], tetrandrine [196], polyphenols [197], citalopram [198], brimonidine [199], amodiaquine [200], methamphetamine [201], platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) [202], tuberculosis [203], oligonucleotide therapeutics [204,205], irinotecan [206], amitriptyline [207], retigabine [208], dufulin [209], nicotine and mannitol [210], cocaine, benzoylecgonine, and cocaethylene [211], irinotecan [206], fosdevirine [212], l-DOPA [213], as well as seasonal trivalent influenza vaccine [214] among others.…”