Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn

Factorial design tool applied for development of isocratic reversed-phase stability-indicating HPLC method for the analysis of mycophenolate mofetil (MMF) and its degradation products. MMF stress degradation products mycophenolate acid (MPA) and DP3 (USP impurity H) were isolated and used for quantitation. Separation achieved on a Symmetry C18 (250 mm × 4.6 mm, 5.0 μ) column using a methanol: acetate buffer (75 : 25 v/v), pH 6.0 (adjusted with acetic acid), at 0.5 mL flow rate, column maintained at 55°C, and data integrated at 251 nm. MMF is subjected to hydrolysis, oxidation, heat degradation, and so forth; under all these conditions degraded products are well separated. The method validation characteristics included accuracy, precision, linearity, range, specificity, and sensitivity. Robustness testing is conducted to evaluate the effect of minor changes to the chromatographic conditions and to establish appropriate system suitability parameters. The proposed method is used to investigate kinetics of acid, alkali hydrolysis and oxidation process. Major degradation products MPA and DP3 were isolated and quantitated. Characterization of MPA by NMR and LC-MS/MS and other degraded products by LC-MS/MS is attempted successfully. The method is used successfully for the quality assessment of three MMF drug commercial formations and its acid, alkali, and oxidative degradation kinetics study.

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Chemistry of renieramycins. Part 6: Transformation of renieramycin M into jorumycin and renieramycin J including oxidative degradation products, mimosamycin, renierone, and renierol acetate

Tetrahedron ◽

10.1016/j.tet.2004.02.071 ◽

2004 ◽

Vol 60 (17) ◽

pp. 3873-3881 ◽

Cited By ~ 37

Author(s):

Naoki Saito ◽

Chieko Tanaka ◽

Yu-ichi Koizumi ◽

Khanit Suwanborirux ◽

Surattana Amnuoypol ◽

...

Keyword(s):

Degradation Products ◽

Oxidative Degradation

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Electrochemical degradation of quercetin: Isolation and structural elucidation of the degradation products

Electrochemistry Communications ◽

10.1016/j.elecom.2007.06.026 ◽

2007 ◽

Vol 9 (9) ◽

pp. 2246-2255 ◽

Cited By ~ 61

Author(s):

Ailing Zhou ◽

Samuel Kikandi ◽

Omowunmi A. Sadik

Keyword(s):

Degradation Products ◽

Structural Elucidation ◽

Electrochemical Degradation

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LC-MS-(MS) determination of oxidative degradation products of nonylphenol ethoxylates, carboxylates and nonylphenols in water

Water Science & Technology ◽

10.2166/wst.2004.0332 ◽

2004 ◽

Vol 50 (5) ◽

pp. 227-234 ◽

Cited By ~ 14

Author(s):

M. Petrovic ◽

P. Gehringer ◽

H. Eschweiler ◽

D. Barceló

Keyword(s):

Electron Beam ◽

Electron Beam Irradiation ◽

Limit Of Detection ◽

Degradation Products ◽

Oxidative Degradation ◽

Nonylphenol Ethoxylates ◽

Beam Irradiation ◽

Treatment Processes ◽

By Products

A commercial blend of nonylphenol ethoxylates (NPEOs) was chosen as representative for non-ionic polyethoxylated surfactants to study the oxidative degradation of this class of surfactants in water using ozonation as well as electron beam irradiation with and without the addition of ozone as treatment processes. The electron beam irradiation processes applied represent so-called Advanced Oxidation Processes (AOPs); the combined ozone/electron beam irradiation is, moreover, the most powerful AOP which can be applied in aqueous systems. It was found that both ozonation and the two AOPs applied were able to decompose not only the NPEOs but also the polyethyleneglycoles (PEGs) formed as by-products from NPEO degradation to residual concentrations below the limit of detection. Moreover, the treatment processes were also used to study the oxidative degradation of nonylphenoxy acetic acid (NPEC) and of nonylphenol (NP) which are formed as by-products from biodegradation of NPEOs.

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Oxidation of Plasmalogens Produces Highly Effective Modulators of Macrophage Function

Zeitschrift für Naturforschung C ◽

10.1515/znc-2000-1-221 ◽

2000 ◽

Vol 55 (1-2) ◽

pp. 115-120 ◽

Cited By ~ 2

Author(s):

Helmut Heinle ◽

Nadja Gugeler ◽

Roswitha Felde ◽

Dagmar Okech ◽

Gerhard Spiteller

Keyword(s):

Degradation Products ◽

Oxidative Degradation ◽

Oxidative Modification ◽

Oxygen Species ◽

Cytotoxic Effects ◽

Macrophage Function ◽

Enhanced Chemiluminescence ◽

Derivatives Of ◽

Assay Conditions

Abstract Model derivatives of plasmalogens and chemically synthesized oxidative degradation products as found e.g. during oxidation of low density lipoproteins show strong effects on phagocytosis induced secretion of reactive oxygen species of macrophages which was measured by luminol-enhanced chemiluminescence. Whereas a plasmalogen epoxide showed enhancing effects in submicromolar range, inhibition was found with higher concentrations as well as with a-hydroxyaldehydes. The substances showed only little effects on the non-cellular ROSdependent chemiluminescence of the reaction between hydrogen peroxide and opsonized zymosan and no cytotoxic effects under the assay conditions used. These results show that oxidative modification and degradation of plasmalogens occuring also under pathophysiological situations in vivo produces effective modulators of macrophage function which could be important; e.g. during inflammation or atherogenesis.

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RP-HPLC assay method development for Paracetamol and Lornoxicam in combination and characterization of oxidative degradation products of Lornoxicam

Chemical Industry and Chemical Engineering Quarterly ◽

10.2298/ciceq120404084j ◽

2013 ◽

Vol 19 (4) ◽

pp. 471-484

Author(s):

Pritam Jain ◽

Miketa Patel ◽

Amar Chaudhari ◽

Sanjay Surana

Keyword(s):

Method Development ◽

Degradation Products ◽

Oxidative Degradation ◽

Assay Method ◽

Forced Degradation ◽

Control Analysis ◽

Reverse Phase ◽

Solution Form ◽

Forced Degradation Studies ◽

Degradation Studies

A simple, specific, accurate and precise reverse phase high pressure liquid chromatographic method has been developed for the simultaneous determination of Paracetamol and Lornoxicam from tablets and to characterize degradation products of Lornoxicam by reverse phase C18 column (Inertsil ODS 3V C-18, 250 x 4.6 mm, 5 ?). The sample was analyzed using Buffer (0.02504 Molar): Methanol in the ratio of 45:55, as a mobile phase at a flow rate of 1.5 mL/min and detection at 290 nm. The retention time for Paracetamol and Lornoxicam was found to be 2.45 and 9.40 min respectively. The method can be used for estimation of combination of these drugs in tablets. The method was validated as per ICH guidelines. The linearity of developed method was achieved in the range of 249.09 - 747.29 ?g/mL (r2=0.9999) for Paracetamol and 4.0125 - 12.0375 ?g/mL (r2=0.9999) for Lornoxicam. Recoveries from tablets were between 98 and 102%. The method was validated with respect to linearity, accuracy, precision, robustness and forced degradation studies which further proved the stability-indicating power. During the forced degradation studies lornoxicam was observed to be labile to alkaline hydrolytic stress and oxidative stress (in the solution form). However, it was stable to the acid hydrolytic, photolytic and thermal stress (in both solid and solution form). The degraded products formed were investigated by electrospray ionization (ESI) time-of-flight mass spectrometry, NMR and IR spectroscopy. A possible degradation pathway was outlined based on the results. The method was found to be sensitive with a detection limit of 0.193 ?g/ml, 2.768 ?g/ml and a quantitation limit of 0.638 ?g/ml, 9.137 ?g/ml for lornoxicam and paracetamol, respectively. Due to these attributes, the proposed method could be used for routine quality control analysis of these drugs in combined dosage forms.

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Isolation and Structure Determination of Echinochrome A Oxidative Degradation Products

Molecules ◽

10.3390/molecules25204778 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4778

Author(s):

Natalia P. Mishchenko ◽

Elena A. Vasileva ◽

Andrey V. Gerasimenko ◽

Valeriya P. Grigorchuk ◽

Pavel S. Dmitrenok ◽

...

Keyword(s):

Mass Spectrometry ◽

Degradation Products ◽

Lethal Dose ◽

Oxidative Degradation ◽

Degradation Process ◽

Oxidation Products ◽

Chemical Mechanism ◽

Ionization Mass ◽

Echinochrome A ◽

Esi Ms

Echinochrome A (Ech A, 1) is one of the main pigments of several sea urchin species and is registered in the Russian pharmacopeia as an active drug substance (Histochrome®), used in the fields of cardiology and ophthalmology. In this study, Ech A degradation products formed during oxidation by O2 in air-equilibrated aqueous solutions were identified, isolated, and structurally characterized. An HPLC method coupled with diode-array detection (DAD) and mass spectrometry (MS) was developed and validated to monitor the Ech A degradation process and identify the appearing compounds. Five primary oxidation products were detected and their structures were proposed on the basis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) as 7-ethyl-2,2,3,3,5,7,8-heptahydroxy-2,3-dihydro-1,4-naphthoquinone (2), 6-ethyl-5,7,8-trihydroxy-1,2,3,4-tetrahydronaphthalene-1,2,3,4-tetraone (3), 2,3-epoxy-7-ethyl-2,3-dihydro-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (4), 2,3,4,5,7-pentahydroxy-6-ethylinden-1-one (5), and 2,2,4,5,7-pentahydroxy-6-ethylindane-1,3-dione (6). Three novel oxidation products were isolated, and NMR and HR-ESI-MS methods were used to establish their structures as 4-ethyl-3,5,6-trihydroxy-2-oxalobenzoic acid (7), 4-ethyl-2-formyl-3,5,6-trihydroxybenzoic acid (8), and 4-ethyl-2,3,5-trihydroxybenzoic acid (9). The known compound 3-ethyl-2,5-dihydroxy-1,4-benzoquinone (10) was isolated along with products 7–9. Compound 7 turned out to be unstable; its anhydro derivative 11 was obtained in two crystal forms, the structure of which was elucidated using X-ray crystallography as 7-ethyl-5,6-dihydroxy-2,3-dioxo-2,3-dihydrobenzofuran-4-carboxylic acid and named echinolactone. The chemical mechanism of Ech A oxidative degradation is proposed. The in silico toxicity of Ech A and its degradation products 2 and 7–10 were predicted using the ProTox-II webserver. The predicted median lethal dose (LD50) value for product 2 was 221 mg/kg, and, for products 7–10, it appeared to be much lower (≥2000 mg/kg). For Ech A, the predicted toxicity and mutagenicity differed from our experimental data.

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