Mass spectrometry imaging and its application in pharmaceutical research and development: A concise review

Swales, John G.; Hamm, Grégory; Clench, Malcolm R.; Goodwin, Richard J. A.

doi:10.1016/j.ijms.2018.02.007

Cited by 125 publications

(130 citation statements)

References 154 publications

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“…[18][19][20] Of all MSI ionization techniques, matrix-assisted laser desorption/ionization (MALDI) is the most popular, [21][22][23][24][25] particularly for imaging of pharmaceuticals. 26,27 A number of recent review articles have summarized the state-of-the-art of the topic. [28][29][30][31][32] One of the most promising applications for MSI is the measurement of the spatial distribution of xenobiotics in CNS tissue.…”

Section: Introductionmentioning

confidence: 99%

Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

et al. 2018

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Tissue-specific ion suppression is an unavoidable matrix effect in MALDI mass spectrometry imaging (MSI), the negative impact of which on precision and accuracy in quantitative MALDI-MSI can be reduced to some extent by applying isotope internal standards for normalization and matrix-matched calibration routines. The detection sensitivity still suffers, however, often resulting in significant loss of signal for the investigated analytes.An MSI application considerably affected by this phenomenon is the quantitative spatial analysis of central nervous system (CNS) drugs. Most of these drugs are low molecular weight, lipophilic compounds, which exhibit inefficient desorption and ionization during MALDI using conventional polar acidic matrices (CHCA, DHB). Here, we present the application of the (2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile) matrix for high sensitivity imaging of CNS drugs in mouse brain sections. Since DCTB is usually described as electron-transfer matrix, we provide a rationale (i.e. computational calculations of gas-phase proton affinity and ionization energy) for an additional protontransfer ionization mechanism with this matrix. Furthermore, we compare the extent of signal suppression for five different CNS drugs when employing DCTB versus CHCA matrices. The results showed that the signal suppression was not only several times lower with DCTB than with CHCA, but also depended on the specific tissue investigated. Finally, we present the application of DCTB and ultra-high resolution Fourier-transform ion cyclotron resonance mass spectrometry to quantitative MALDI imaging of the anesthetic drug xylazine in mouse brain sections based on a linear matrix-matched calibration curve. DCTB afforded up to 100fold signal intensity improvement over CHCA when comparing representative single MSI pixels, and > 440-fold for the averaged mass spectrum of the adjacent tissue sections.

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Section: Introductionmentioning

confidence: 99%

Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

et al. 2018

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“…Mass spectrometry imaging (MSI) provides spatial information on parent drug, drug metabolites and/or endogenous compounds (e.g., identification of biomarkers) on whole body or tissue slices without the need for any (radio)labeling . MSI has been around for more than two decades but its popularity in many fields, including ADME‐related analyses, has exponentially grown lately due to ever increasing HRMS (mainly sensitivity and MS resolution) and laser technology (mainly spatial resolution) performance. It provides complementary information to traditional methods such as tissue extraction followed by LC/MS analysis that suffers from the absence of spatial information and whole body autoradiography that lacks the specificity to resolve the parent drug from its metabolites.…”

Section: Ms Imagingmentioning

confidence: 99%

Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives

Cuyckens

2018

Rapid Comm Mass Spectrometry

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Drug Metabolism and Pharmacokinetics (DMPK) is a core scientific discipline within drug discovery and development as well as post-marketing. It helps to design and select the most promising drug candidate and obtain advanced insights on the processes that control absorption, distribution, metabolism and excretion (ADME) of the final drug candidate. Mass spectrometry is one of the key technologies applied in DMPK. Therefore, the continuous advances made in the field of mass spectrometry also directly impact the way in which we investigate the ADME properties of a compound, providing us with new tools to gather more information or improve our efficiency. An overview will be given of some important current trends and future perspectives in the field.

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“…Owing to its high chemical specificity and ability to track hundreds of analytes simultaneously, MALDI-MSI has gained traction in various areas of biomolecular research such as quantitative profiling of metabolites, lipids, peptides, proteins and drugs (1)(2)(3)(4). In the latter case, MALDI-MSI has found its way into pharmaceutical research and development, where disposition of drugs and their carriers can be effectively monitored alongside their pharmacodynamics and toxic effects (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, quantitative assessment of drug distribution in patient tissues employs bioanalytical techniques such as UPLC-ESI-MS, which assume homogenous distribution of analytes and require tissue homogenization resulting in a complete loss of spatial context (5). In contrast, MALDI-MSI provides spatial information, and much effort has recently been devoted to establish quantitative MSI (qMSI) techniques (1)(2)(3)(4)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib Penetration into Liver Metastases of Gastrointestinal Stromal Tumors

Sammour

Marsching

Geisel

et al. 2019

Preprint

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Mass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science-and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 28 imatinib-treated patients with biopsy-proven gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI. We introduced a novel generalized nonlinear calibration model of drug quantities based on focused computational evaluation of drug-containing areas that enabled better data fitting and assessment of the inherent method nonlinearities. Imatinib tissue spatial maps revealed striking inefficiency in drug penetration into GIST liver metastases even though the corresponding healthy liver tissues in the vicinity showed abundant imatinib levels beyond the limit of quantification (LOQ), thus providing evidence for secondary drug resistance independent of mutation status. Taken together, these findings underline the important application of MALDI-qMSI for studying the spatial distribution of molecularly targeted therapeutics in oncology.

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Mass spectrometry imaging and its application in pharmaceutical research and development: A concise review

Cited by 125 publications

References 154 publications

Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives

Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib Penetration into Liver Metastases of Gastrointestinal Stromal Tumors

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