Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of Rifampicin in Liver Tissues

Chumbley, Chad W.; Reyzer, Michelle L.; Allen, James L.; Marriner, Gwendolyn A.; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

doi:10.1021/acs.analchem.5b04409

Cited by 155 publications

(189 citation statements)

References 42 publications

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“…Absolute quantitative analysis by MSI has posed a real challenge and only now are the first publications starting to appear, demonstrating its feasibility40. While absolute quantification of PTX was beyond the scope of this work, we estimated PTX concentration in the different tumor volumes, correlating the different PTX ion signal intensity ranges to the concentration values of a calibration curve.…”

Section: Resultsmentioning

confidence: 99%

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Giordano

Morosi

Veglianese

et al. 2016

Sci Rep

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Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.

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Section: Resultsmentioning

confidence: 99%

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Giordano

Morosi

Veglianese

et al. 2016

Sci Rep

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“…Hence, the sampling sizes achieved herein represent a significant improvement in spatial resolution for quantitative analysis of drugs in tissue. 9,16,26,47,49 It is worth noting that, once an external calibration curve was generated (∼1 h), quantitation could be achieved in seconds after cutting and dropping an individual sample. Furthermore, additional tissue preparation beyond sectioning and mounting was not required prior to analysis.…”

Section: ■ Conclusionmentioning

confidence: 99%

Online, Absolute Quantitation of Propranolol from Spatially Distinct 20- and 40-μm Dissections of Brain, Liver, and Kidney Thin Tissue Sections by Laser Microdissection–Liquid Vortex Capture–Mass Spectrometry

et al. 2016

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Spatial resolved quantitation of chemical species in thin tissue sections by mass spectrometric methods has been constrained by the need for matrix-matched standards or other arduous calibration protocols and procedures to mitigate matrix effects (e.g., spatially varying ionization suppression). Reported here is the use of laser "cut and drop" sampling with a laser microdissection-liquid vortex capture electrospray ionization tandem mass spectrometry (LMD-LVC/ESI-MS/MS) system for online and absolute quantitation of propranolol in mouse brain, kidney, and liver thin tissue sections of mice administered with the drug at a 7.5 mg/kg dose, intravenously. In this procedure either 20 μm × 20 μm or 40 μm × 40 μm tissue microdissections were cut and dropped into the flowing solvent of the capture probe. During transport to the ESI source drug related material was completely extracted from the tissue into the solvent, which contained a known concentration of propranolol-d7 as an internal standard. This allowed absolute quantitation to be achieved with an external calibration curve generated from standards containing the same fixed concentration of propranolol-d7 and varied concentrations of propranolol. Average propranolol concentrations determined with the laser "cut and drop" sampling method closely agreed with concentration values obtained from 2.3 mm diameter tissue punches from serial sections that were extracted and quantified by HPLC/ESI-MS/MS measurements. In addition, the relative abundance of hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous findings.

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“…A validated quantitative IMS approach was recently developed in which an isotopically labeled standard was deposited using a robotic spotter in an array of microspots (~200 μm in diameter) across a liver tissue section dosed with a drug [34]. Calibration standards were deposited on a non-dosed tissue section and analyzed in the same way as those on the dosed tissue.…”

Section: Quantitative Ims: a Prerequisite For Its Use In Toxicologicamentioning

confidence: 99%

“…The results from IMS and HPLC-MS/MS were in agreement for the entire tissue section, and the image provides additional information about the localization of PMZ to the cortex region of the kidney. Adapted from Chumbley et al [34] with permission. Copyright 2016 American Chemical Society.…”

Section: Figmentioning

confidence: 99%

Potential of MALDI imaging for the toxicological evaluation of environmental pollutants

Lagarrigue

Caprioli

Pineau

2016

Journal of Proteomics

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Risk assessment related to the exposure of humans to chemicals released into the environment is a major concern of our modern societies. In this context, toxicology plays a crucial role to characterize the effects of this exposure on health and identify the targets of these molecules. MALDI imaging mass spectrometry (IMS) is an enabling technology for biodistribution studies of chemicals. Although the majority of published studies are presented in a pharmacological context, the concepts discussed in this review can be applied to the toxicological evaluation of chemicals released into the environment. The major asset of IMS is the simultaneous localization and identification of a parent molecule and its metabolites without labeling and without any prior knowledge. Quantification methods developed in IMS are presented with application to an environmental pollutant. IMS is effective in the localization of chemicals and endogenous species. This opens unique perspectives for the discovery of molecular alterations in metabolites and protein biomarkers that could help for a better understanding of toxicity mechanisms. Distribution studies of agrochemicals in plants by IMS can contribute to a better understanding of their mode of action and to a more effective use of these chemicals, avoiding the current concern of environmental damage.

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Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of Rifampicin in Liver Tissues

Cited by 155 publications

References 42 publications

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Online, Absolute Quantitation of Propranolol from Spatially Distinct 20- and 40-μm Dissections of Brain, Liver, and Kidney Thin Tissue Sections by Laser Microdissection–Liquid Vortex Capture–Mass Spectrometry

Potential of MALDI imaging for the toxicological evaluation of environmental pollutants

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