Stability Testing

Clapham, David

doi:10.1002/9781118971147.ch2

Cited by 50 publications

(2 citation statements)

References 27 publications

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“…The structures of degradation products and the mechanics of their formation were designed in accordance with the information on the mass of quasi-molecular ions and fragmented degradation products using the DataAnalysis Program [ 29 ]. The structure of the degradation products and the mechanisms of their formation were deduced based on information on the mass of quasi-molecular ions and fragmented degradation products based on previous information and literature reports [ 27 , 30 ]. The chromatogram of the sample solution and the proposed E – I imide degradation pathways are shown in Scheme 4 , Scheme 5 and Scheme 6 and in additional materials: I ( E ), II ( F ), III ( G ), IV ( H ), and V ( I ).…”

Section: Resultsmentioning

confidence: 99%

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A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

Szkatuła

Krzyżak

Stanowska

et al. 2021

IJMS

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Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.

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Section: Resultsmentioning

confidence: 99%

“…The instability of the piperazine ring has been previously described for fluoroquinolone derivatives. Not all fragmentation products have been solved ( Scheme 4 , m/z = 307; Scheme 5 , m/z = 375), for some, they have not been confirmed in the literature [ 27 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

Szkatuła

Krzyżak

Stanowska

et al. 2021

IJMS

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Integrative analysis of tepotinib forced degradation: Combining in‐silico and liquid chromatography‐quadrupole time‐of‐flight‐tandem mass spectrometry approaches for structural elucidation

Mahajan,

Bishnani,

Sapkal

et al. 2024

Separation Science Plus

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The present research aimed to comprehensively investigate the forced degradation of tepotinib through a combined in‐silico and experimental analysis. Tepotinib is a recently approved drug for metastatic non‐small cell lung cancer. A short and precise ultra‐high‐performance liquid chromatography (UHPLC) method utilizing a CSH C18 column (100 × 2.1 mm, 1.7 μm) was developed, using a mobile phase A as 0.1% formic acid and mobile phase B as HPLC‐grade acetonitrile. The flow rate was set at 0.2 mL/min, and detection was carried out at 260 nm. Forced degradation was carried out under acidic, basic, oxidative, and photolytic environments and also virtually with Zeneth software. Structural characterization of degradation products (DPs) was carried out using hyphenated techniques such as LC‐quadrupole time‐of‐flight‐tandem mass spectrometry in positive electrospray ionization mode. Further, toxicity was assessed with Derek and Sarah software. Analysis revealed the formation of five distinct forced DPs: DP‐1 (m/z 511), DP‐2 (m/z 527), DP‐3 (m/z 525), DP‐4 (m/z 512), and DP‐5 (m/z 509) under experimental conditions and eight in Zeneth prediction. Furthermore, nephrotoxicity alerts were observed for DP‐3 and DP‐5, whereas DP‐3 also showed mutagenicity alerts. This integrated blend of in‐silico and real experimental analyses was found to be effective in quality control for routing monitoring of degradation products of tepotinib.

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