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Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis 下载免费PDF全文
Prinesh N. Patel Roshan M. Borkar Pradipbhai D. Kalariya Rahul P. Gangwal Abhay T. Sangamwar Gananadhamu Samanthula Srinivas Ragampeta 《Journal of mass spectrometry : JMS》2015,50(2):344-353
A validated stability‐indicating HPLC method was established, and comprehensive stress testing of ivabradine, a cardiotonic drug, was carried out as per ICH guidelines. Ivabradine was subjected to acidic, basic and neutral hydrolysis, oxidation, photolysis and thermal stress conditions, and the resulting degradation products were investigated by LC‐PDA and LC‐HR‐MS/MS. The drug was found to degrade in acid and base hydrolysis. An efficient and selective stability assay method was developed on Phenomenex Luna C18 (250 × 4.6 mm, 5.0 µm) column using ammonium formate (10 mM, pH 3.0) and acetonitrile as mobile phase at 30 °C in gradient elution mode. The flow rate was 0.7 ml/min and detection wavelength was 286 nm. A total of five degradation products (I‐1 to I‐5) were identified and characterized by LC‐HR‐MS/MS in combination with accurate mass measurements. The drug exhibited different degradation behaviour in HCl and H2SO4 hydrolysis conditions. It is a unique example where two of the five degradation products in HCl hydrolysis were absent in H2SO4 acid hydrolysis. The present study provides guidance to revise the stress test for the determination of inherent stability of drugs containing lactam moiety under hydrolytic conditions. Most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation pattern of the drug and its degradation products. In silico toxicity revealed that the degradation products ( I‐2 to I‐5 ) were found to be severe irritants in case of ocular irritancy. The analytical assay method was validated with respect to specificity, linearity, range, precision, accuracy and robustness. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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CoFe2O4-BaTiO3 composites were prepared using conventional ceramic double sintering process with various compositions. Presence of two phases
in the composites was confirmed using X-ray diffraction. The dc resistivity and thermoemf as a function of temperature in
the temperature range 300 K to 600 K were measured. Variation of dielectric constant (ɛ′) with frequency in the range 100 Hz to 1 MHz and also with temperature at a fixed frequency of 1 kHz was studied. The ac
conductivity was derived from dielectric constant (ɛ′) and loss tangent (tan δ). The nature of conduction is discussed on the basis of small polaron hopping model. The static value of magnetoelectric
conversion factor has been studied as a function of magnetic field. 相似文献
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Anuseema Bhadauriya Gaurao V. Dhoke Rahul P. Gangwal Mangesh V. Damre Abhay T. Sangamwar 《Molecular diversity》2013,17(1):139-149
Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated $\text{ IC}_{50}$ value, quantitative estimation of drug-likeness and molecular docking analysis. Finally, three novel compounds with diverse scaffolds were selected as potential starting points for the design of novel dual ACC inhibitors. 相似文献
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The application of ac electric fields in aqueous suspensions of anisotropic particles leads to unbalanced liquid flows and nonlinear, induced-charge electrophoretic motion. We report experimental observations of the motion of Janus microparticles with one dielectric and one metal-coated hemisphere induced by uniform fields of frequency 100 Hz-10 kHz in NaCl solutions. The motion is perpendicular to the field axis and persists after particles are attracted to a glass wall. This phenomenon may find applications in microactuators, microsensors, and microfluidic devices. 相似文献
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DJ Smith KW Ledingham RP Singhal T McCanny P Graham HS Kilic P Tzallas C Kosmidis AJ Langley PF Taday 《Rapid communications in mass spectrometry : RCM》1999,13(14):1366-1373
With the development of high intensity femtosecond lasers, the ionisation and dissociation dynamics of molecules has become an area of considerable interest. Using the technique of femtosecond laser mass spectrometry (FLMS), the molecules carbon disulphide, pyrimidine, toluene, cyclohexanone and benzaldehyde are studied with pulse widths of 50 fs in the near infrared (IR) wavelength region (790 nm). Results are presented and contrasted for laser beam intensities around 10(15) and 10(16) W cm(-2). For the lower intensities, the mass spectra yield dominant singly charged parent ions. Additionally, the appearance of doubly charged parent ions is evident for carbon disulphide, toluene and benzaldehyde with envelopes of doubly charged satellite species existing in these local regions. Carbon disulphide also reveals a small triply charged component. Such atomic-like features are thought to be a strong fingerprint of FLMS at these intensities. However, upon increasing the laser intensity to approximately 10(16) W cm(-2), parent ion dominance decreases and the appearance of multiply charged atomic species occurs, particularly carbon. This phenomenon has been attributed to Coulomb explosions in which the fast absorption of many photons may produce transient highly ionised parent species which can subsequently blow apart. Copyright 1999 John Wiley & Sons, Ltd. 相似文献
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X Fang KW Ledingham P Graham DJ Smith T McCanny RP Singhal AJ Langley PF Taday 《Rapid communications in mass spectrometry : RCM》1999,13(14):1390-1397
The potential of femtosecond laser time-of-flight mass spectrometry (FLMS) for uniform quantitative analysis of molecules has been investigated. Various samples of molecular gases and vapours have been studied, using ultra-fast ( approximately 50 fs) laser pulses with very high intensity (up to 1.6 x 10(16) Wcm(-2)) for non-resonant multiphoton ionisation/tunnel ionisation. Some of these molecules have high ionisation potentials, requiring up to ten photons for non-resonant ionisation. The relative sensitivity factors (RSF) have been determined as a function of the laser intensity and it has been demonstrated that for molecules with very different masses and ionisation potentials, uniform ionisation has been achieved at the highest laser intensities. Quantitative laser mass spectrometry of molecules is therefore a distinct possibility. Copyright 1999 John Wiley & Sons, Ltd. 相似文献