Dataset Information

Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

ABSTRACT: Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

SUBMITTER: Swales JG

PROVIDER: S-EPMC5121636 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

Swales John G JG Strittmatter Nicole N Tucker James W JW Clench Malcolm R MR Webborn Peter J H PJH Goodwin Richard J A RJA

Scientific reports 20161124

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viabl ...[more]

PMID: 27883030

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Project description:The distribution of active compounds of traditional Chinese medicine Salvia miltiorrhiza Bunge (Chinese name: Danshen) in vivo was determined by establishing a liquid extraction surface analysis coupled with the tandem mass spectrometry (LESA-MS/MS) method. Stability analysis and distribution analysis were designed in the present study using normal animals or a myocardial ischemia model. The model assessment was performed four weeks after surgery, and then three groups were created: a normal-dose group, a model-blank group, and a model-dose group. Meanwhile, Danshen decoction administration began in dose groups and lasted for four weeks. In stability analysis, four salvianolic acids-Danshensu (DSS), caffeic acid (CAA), rosmarinic acid (RA), and salvianolic acid A (SAA)-in kidney tissues from the normal-dose group were detected by LESA-MS/MS under four conditions, and then distribution analysis was conducted in different tissues using the same method. Ejection fraction (EF) and fractional shortening (FS) in animals from two model groups decreased significantly four weeks after surgery (P < 0.01) and were improved after four weeks of Danshen decoction administration (P < 0.01). Results of stability analysis demonstrated that this method was basically stable since there were no significant differences in signal intensities of DSS, CAA, and SAA under four conditions (P > 0.05). Distribution analysis showed the signal intensities of DSS in the liver and kidney and SAA in the heart were higher in the model-dose group than in the normal-dose group (P < 0.05 or P < 0.01). Signal intensities of RA in the liver and kidney, and SAA in the liver were lower in the model-dose group compared with the normal-dose group (P < 0.05 or P < 0.01). In conclusion, Danshen decoction has the effect of improving the ischemic condition in a chronic myocardial ischemia model, and the content of two active compounds increased in the targets. These findings contribute to an understanding of the therapeutic role of Danshen in cardiovascular disease.

Dataset Information

Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

Publications

Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

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