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3. Study on the impurity profiles of cloxacillin and flucloxacillin based on liquid chromatography tandem ion trap/time‐of‐flight mass spectrometry.

Author

Xu, Bingyong, Gao, Jiarui, Wang, Jian, and Wang, Fan

Subjects
*LIQUID chromatography, *ION exchange chromatography, *MASS spectrometry, *HIGH performance liquid chromatography, *GRADIENT elution (Chromatography), *TIME-of-flight mass spectrometry, *PENNING trap mass spectrometry, *LIQUID chromatography-mass spectrometry, *ION traps
Abstract

Rationale: Cloxacillin and flucloxacillin are prone to degradation and polymerization in humid and hot environments, and their polymers have long been recognized to trigger allergic manifestations. A series of the degradation and polymerized impurities in cloxacillin and flucloxacillin were separated and characterized to ensure safe use of these drugs by the public. Methods: By studying the chromatographic behavior of the degradation impurities and polymerized impurities in reversed‐phase high‐performance liquid chromatography (RP‐HPLC) gradient elution, the impurities in cloxacillin and flucloxacillin were effectively separated and eluted. RP‐HPLC tandem ion trap/time‐of‐flight mass spectrometry (MS) was applied to characterize the structures of unknown impurities eluted from the RP‐HPLC methods for cloxacillin and flucloxacillin. The mechanisms of formation of the impurities in cloxacillin and flucloxacillin were also investigated. Results: The structures of 10 unknown impurities in cloxacillin and 8 unknown impurities in flucloxacillin were elucidated based on the high‐resolution MSn data at positive and negative modes, respectively. Six polymerized impurities were found and characterized, of which three were from the polymerization of cloxacillin and three were from the polymerization of flucloxacillin. Conclusions: The study on the impurity profiles of cloxacillin and flucloxacillin provided a scientific basis for improving their production processes and quality control. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Methyl Gallate Improves Hyperuricemia Nephropathy Mice Through Inhibiting NLRP3 Pathway

Author

Liu, Peng, Wang, Wen, Li, Qiang, Hu, Xin, Xu, Bingyong, Wu, Chen, Bai, Lijie, Ping, Li, Lan, Zhou, and Chen, Lvyi

Subjects
Pharmacology, methyl gallate, integumentary system, NLRP3, uric acid, nephropathy, Pharmacology (medical), ROS, Therapeutics. Pharmacology, RM1-950, Original Research
Abstract

Hyperuricemia nephropathy (HN) is a form of chronic tubulointerstitial inflammation, caused by the deposition of monosodium urate crystals (MSU) in the distal collecting duct and medullary interstitium, associated with a secondary inflammatory reaction. Numerous published reports indicated that NLRP3 inflammasome pathway play crucial roles in HN symptoms. The present study aims to investigate the protective effects of methyl gallate on HN mice and the underlying mechanisms. An HN model was established by intraperitoneal injection of potassium oxide (PO) to assess the effect of methyl gallate on renal histopathological changes, renal function, cytokine levels and expressions of NLRP3-related protein in HN mice. Moreover, in vitro models of lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs) were established to explore the mechanism of methyl gallate on NLRP3 inflammasome activation. The results showed that methyl gallate significantly ameliorated HN by inhibiting uric acid production and promoting uric acid excretion as well as ameliorating renal injury induced by NLRP3 activation. Mechanistically, methyl gallate is a direct NLRP3 inhibitor that inhibits NLRP3 inflammasome activation but has no effect on the activation of AIM2 or NLRC4 inflammasomes in macrophages. Furthermore, methyl gallate inhibited the assembly of NLRP3 inflammasomes by blocking the ROS over-generation and oligomerization of NLRP3. Methyl gallate was also active ex vivo against ATP-treated PBMCs and synovial fluid mononuclear cells from patients with gout. In conclusion, methyl gallate has a nephroprotective effect against PO-induced HN through blocking the oligomerization of NLRP3 and then exerting anti-inflammatory activity in the NLRP3-driven diseases.

Published
2021

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