Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study

Zecchi, Riccardo; Franceschi, Pietro; Tigli, Laura; Amidani, Davide; Catozzi, Chiara; Ricci, Francesca; Salomone, Fabrizio; Pieraccini, Giuseppe; Pioselli, Barbara; Mileo, Valentina

doi:10.1007/s00216-021-03393-6

Cited by 15 publications

(16 citation statements)

References 42 publications

(42 reference statements)

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“…Further studies will be needed to optimize MSI for the assessment of ZF larvae considering various classes of drugs. We plan to further investigate MSI for ZF larvae by applying existing and optimized methods using ZF larvae homogenates [49][50][51] in order to account for possible deviations based on different tissue types [49] and local interfering molecules [45].…”

Section: Spatial Distribution Of 4f-mdmb-binaca and Its Metabolites I...mentioning

confidence: 99%

Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

et al. 2022

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Zebrafish (ZF; Danio rerio) larvae have become a popular in vivo model in drug metabolism studies. Here, we investigated the metabolism of methyl 2-[1-(4-fluorobutyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate (4F-MDMB-BINACA) in ZF larvae after direct administration of the cannabinoid via microinjection, and we visualized the spatial distributions of the parent compound and its metabolites by mass spectrometry imaging (MSI). Furthermore, using genetically modified ZF larvae, the role of cannabinoid receptor type 1 (CB1) and type 2 (CB2) on drug metabolism was studied. Receptor-deficient ZF mutant larvae were created using morpholino oligonucleotides (MOs), and CB2-deficiency had a critical impact on liver development of ZF larva, leading to a significant reduction of liver size. A similar phenotype was observed when treating wild-type ZF larvae with 4F-MDMB-BINACA. Thus, we reasoned that the cannabinoid-induced impaired liver development might also influence its metabolic function. Studying the metabolism of two synthetic cannabinoids, 4F-MDMB-BINACA and methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB), revealed important insights into the in vivo metabolism of these compounds and the role of cannabinoid receptor binding.

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Section: Spatial Distribution Of 4f-mdmb-binaca and Its Metabolites I...mentioning

confidence: 99%

Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

et al. 2022

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“…However, the poor ionization of budesonide in lung tissue prevented us from the application of this strategy. To increase the budesonide signal, an on-tissue derivatization step with the GirP reactant had to be performed, as recently described by Zecchi et al [16], which required a dedicated sample preparation. Therefore, SP-C and budesonide images were obtained from consecutive tissue sections.…”

Section: Discussionmentioning

confidence: 99%

“…Budesonide is challenging to detect by MSI as it is not easily protonated or deprotonated. Therefore, to improve the detection of budesonide in lung tissue sections, an on-tissue chemical derivatization protocol was adopted as recently described by Zecchi et al [16]. Briefly, this approach uses GirP as an on tissue derivatizing agent, followed by FA matrix coating.…”

Section: Sample Preparation and Maldi-msi Analysis For Budesonide Det...mentioning

confidence: 99%

Surfactant-Assisted Distal Pulmonary Distribution of Budesonide Revealed by Mass Spectrometry Imaging

et al. 2021

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Direct lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lung.

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“…通常情况下, 萜类植物激素: 如脱落酸(abscisic acid, [207] . Zecchi 等人 [127] [120,123] 是一种常用的加成衍生化试剂, 其结合激光辅助组织转移 (laser-assisted tissue transfe, LATT)技术可以增强小分子组织原位衍生化效率. Guo 等人 [123]…”

Section: F O R R E V I E W O N L Yunclassified

Chemical derivatization: recent advances in mass spectrometry imaging

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Qin²,

Jiang³

et al. 2022

Sci. Sin.-Chim

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Recently, mass spectrometry imaging (MSI) has been drawing more and more attention due to its continuous development and improvement as well as its vital role in the study of biological science. Many MSI-based strategies have been widely applied to the in situ qualitative and quantitative detection and imaging of endogenous/exogenous molecules in tissues. Among, matrix assisted laser desorption/ionization MSI (MALDI-MSI) and desorption electrospray ionization MSI (DESI-MSI) are generally regarded as two the most commonly used molecular imaging techniques. Although MSI, as a histology-based emerging molecular imaging technique, has significant advantages over other imaging techniques because it is a label-free technique which provides high sensitivity, high throughput, and molecular specificity derived from the use of mass spectrometers as detectors for a wide variety of ionized biomolecules in situ within a tissue section, it still has obvious shortcomings in the in situ analysis of low-polarity and neutral biomolecules. To solve this issue, the application of chemical derivatization technology in MSI is one of the most important approaches to overcome these deficiencies of MS molecular imaging. This review provides an overview of various chemical derivatization techniques, such as, esterification derivatization, acylation derivatization, addition reaction derivatization, substitution derivatization, oxidative derivatization, and other derivatizations, used in MS analysis, highlights the application of these chemical derivatization methods in the in situ detection and imaging of biomolecules in tissues by MALDI-MSI and DESI-MSI. It can be predicted that with the advance progress of chemical derivatization technology, the application scope of MSI will be further expanded in the fields of spatial metabolomics, spatial lipidomics, spatial proteomics, and spatial glycomics.

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Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study

Cited by 15 publications

References 42 publications

Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

Surfactant-Assisted Distal Pulmonary Distribution of Budesonide Revealed by Mass Spectrometry Imaging

Chemical derivatization: recent advances in mass spectrometry imaging

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