A new method for screening aldose reductase inhibitors using ultrahigh performance liquid chromatography-tandem mass spectrometry

Hou, Guangyue; Zhang, Ruixing; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

doi:10.1039/c4ay00857j

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…Epalrestat (5-[(1 Z ,2 E )− 2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3-thiazolidie acetic acid), which is approved for human use in Japan, is a carboxylic acid derivative and is currently available for the treatment of diabetic peripheral neuropathy [1], [2], [3], [4], [5], [6], [7]. Diabetic peripheral neuropathy is one of the most common long-term complications in diabetic patients [8], [9], [10].…”

Section: Introductionmentioning

confidence: 99%

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

Sun¹,

Liu

Gao

et al. 2019

Journal of Pharmaceutical Analysis

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Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as different pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A = 1.6 × 105C–1.3 × 103 (r = 0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength; however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.

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Section: Introductionmentioning

confidence: 99%

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

Sun¹,

Liu

Gao

et al. 2019

Journal of Pharmaceutical Analysis

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“…[1] HPLC-MS provides an increasingly convenient and economical means for direct detection of enzymatic products, and thus offers a viable alternative to more limited detection methods. A number of exciting HPLC-MS based inhibition assays have been described recently, [2–4] however, no HPLC-MS based inhibitor assays compatible with lipoxygenase (LOX) enzymes and their hydrophobic substrates/inhibitors have currently been reported.…”

Section: 1 Introductory Statementmentioning

confidence: 99%

A high-throughput mass spectrometric assay for discovery of human lipoxygenase inhibitors and allosteric effectors

Jameson

Kenyon

Holman

2015

Analytical Biochemistry

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Lipoxygenases (LOX) regulate inflammation through the production of a variety of molecules whose specific downstream effects are not entirely understood due to the complexity of the inflammation pathway. The generation of these biomolecules can potentially be inhibited and/or allosterically regulated by small synthetic molecules. The current work describes the first mass spectrometric, high throughput method for identifying small molecule LOX inhibitors and LOX allosteric effectors, which change the substrate preference of human lipoxygenase enzymes. Using a volatile buffer and an acid-labile detergent, enzymatic products can be directly detected using liquid chromatography-mass spectrometry (HPLC-MS), without the need of organic extraction. The method also reduces the required enzyme concentration compared to traditional UV absorbance methods by approximately 30-fold, allowing accurate binding affinity measurements for inhibitors with nanomolar affinity. The procedure was validated using known LOX inhibitors and the allosteric effector, 13(S)-hydroxy-9Z,11E-octadecadienoic acid (13-HODE).

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Quantitative analysis of urinary endogenous markers for the treatment effect of Radix Scutellariae on type 2 diabetes rats

Hou

Men

Wang

et al. 2017

Chinese Chemical Letters

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A new method for screening aldose reductase inhibitors using ultrahigh performance liquid chromatography-tandem mass spectrometry

Abstract: Because aldose reductase as a key enzyme is closely related to diabetic complications, an ultrahigh performance liquid chromatography-tandem mass spectrometry method was developed for screening aldose reductase inhibitors in this study.

Cited by 4 publications

References 29 publications

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

A high-throughput mass spectrometric assay for discovery of human lipoxygenase inhibitors and allosteric effectors

Quantitative analysis of urinary endogenous markers for the treatment effect of Radix Scutellariae on type 2 diabetes rats

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