Desorption Electrospray Ionization Mass Spectrometry Imaging Allows Spatial Localization of Changes in Acetaminophen Metabolism in the Liver after Intervention with 4-Methylpyrazole

Akakpo, Jephte Y.; Jaeschke, M; Etemadi, Yasaman; Artigues, Antonio; Toerber, Scott; Olivos, Hernando J.; Shrestha, Bindesh; Midey, Anthony J.; Jaeschke, Hartmut; Ramachandran, Anup

doi:10.1021/jasms.2c00202

Cited by 15 publications

(13 citation statements)

References 61 publications

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“…27 Other MSI studies of APAP have only focused on liver tissues. 28,29 In this study, we showed the distribution of native APAP and APAP-CYS in mice kidneys at high spatial resolution (25 and 10 μm) by employing iMScope QT. Furthermore, we discovered a novel APAP metabolite in mice kidneys, brains, and liver.…”

Section: ■ Introductionmentioning

confidence: 88%

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Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 μm Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope

Mamun

Rahman

Sakamoto

et al. 2023

J. Am. Soc. Mass Spectrom.

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Drug distribution studies in tissue are crucial for understanding the pharmacokinetics and potential toxicity of drugs. Recently, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) has gained attention for drug distribution studies due to its high sensitivity, label-free nature, and ability to distinguish between parent drugs, their metabolites, and endogenous molecules. Despite these advantages, achieving high spatial resolution in drug imaging is challenging. Importantly, many drugs and metabolites are rarely detectable by conventional vacuum MALDI-MSI because of their poor ionization efficiency. It has been reported that acetaminophen (APAP) and one of its major metabolites, APAP-Cysteine (APAP-CYS), cannot be detected by vacuum MALDI-MSI without derivatization. In this context, we showed the distribution of both APAP and APAP-CYS in kidneys at high spatial resolution (25 and 10 μm) by employing an atmospheric pressure-MALDI imaging mass microscope without derivatization. APAP was highly accumulated in the renal pelvis 1 h after drug administration, while APAP-CYS exhibited characteristic distributions in the outer medulla and renal pelvis at both 30 min and 1 h after administration. Interestingly, cluster-like distributions of APAP and APAP-CYS were observed in the renal pelvis at 10 μm spatial resolution. Additionally, a novel APAP metabolite, tentatively coined as APAP-butyl sulfate (APAP-BS), was identified in the kidney, brain, and liver by combining MSI and tandem MSI. For the first time, our study revealed differential distributions of APAP, APAP-CYS (in kidneys), and APAP-BS (in kidney, brain, and liver) and is believed to enhance the understanding of the pharmacokinetics and potential nephrotoxicity of this drug.

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Section: ■ Introductionmentioning

confidence: 88%

“…Recently, it has been reported that APAP and APAP-CYS cannot be detected by conventional vacuum MALDI, and therefore OTCD has been employed to see their distributions in whole rat body (at 400 μm spatial resolution) and testes (at 50 μm spatial resolution) . Other MSI studies of APAP have only focused on liver tissues. , …”

Section: Introductionmentioning

confidence: 99%

Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 μm Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope

Mamun

Rahman

Sakamoto

et al. 2023

J. Am. Soc. Mass Spectrom.

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“…Mouse liver slices were studied after various APAP dosages to determine the spatial concentration and proliferation of oxidative and nonoxidative byproducts. 64 Signal intensity variations associated with metabolite concentrations could be clearly seen in tissues, and 4MP therapy drastically altered this spatial distribution. The work offered a unique label- and matrix-free framework with outstanding sensitivity to evaluate the regional fluctuations in APAP metabolite concentration post 4MP therapy with a spatial resolution of 50 micron.…”

Section: Ambient Liquid Extraction Techniques and Applicationsmentioning

confidence: 98%

“…4). 64 This was done utilizing DESI-MSI technique. Mouse liver slices were studied after various APAP dosages to determine the spatial concentration and proliferation of oxidative and nonoxidative byproducts.…”

Section: Ambient Liquid Extraction Techniques and Applicationsmentioning

confidence: 99%

Recent developments and applications of ambient mass spectrometry imaging in pharmaceutical research: an overview

Kumar

2024

Anal. Methods

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“…Several other studies have used DESI-MS imaging to study the distribution of drugs in tissues, including acetaminophen and its metabolites in the mouse liver 121 and extracellular signal-regulated kinase inhibitors in mouse brain tissues. 122 Finally, another recent study utilized SESI-MS for the real-time detection of inhaled aerosols in exhaled breath for the purpose of studying the aerosolization performance of inhaled drug products.…”

Section: Pharmaceuticalsmentioning

confidence: 99%

Applications of ambient ionization mass spectrometry in 2022: An annual review

Rankin‐Turner

Sears

Heaney

2023

Analytical Science Advances

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The development of ambient ionization mass spectrometry (AIMS) has transformed analytical science, providing the means of performing rapid analysis of samples in their native state, both in and out of the laboratory. The capacity to eliminate sample preparation and pre‐MS separation techniques, leading to true real‐time analysis, has led to AIMS naturally gaining a broad interest across the scientific community. Since the introduction of the first AIMS techniques in the mid‐2000s, the field has exploded with dozens of novel ion sources, an array of intriguing applications, and an evident growing interest across diverse areas of study. As the field continues to surge forward each year, ambient ionization techniques are increasingly becoming commonplace in laboratories around the world. This annual review provides an overview of AIMS techniques and applications throughout 2022, with a specific focus on some of the major fields of research, including forensic science, disease diagnostics, pharmaceuticals and food sciences. New techniques and methods are introduced, demonstrating the unwavering drive of the analytical community to further advance this exciting field and push the boundaries of what analytical chemistry can achieve.

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Desorption Electrospray Ionization Mass Spectrometry Imaging Allows Spatial Localization of Changes in Acetaminophen Metabolism in the Liver after Intervention with 4-Methylpyrazole

Cited by 15 publications

References 61 publications

Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 μm Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope

Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 μm Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope

Recent developments and applications of ambient mass spectrometry imaging in pharmaceutical research: an overview

Applications of ambient ionization mass spectrometry in 2022: An annual review

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