Isolation and Structural Characterization of Degradation Products of Aceclofenac by HPLC, HRMS and 2D NMR

The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.

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Degradation Studies of Lacidipine: Identification, Isolation and Structural Characterization of Stress Degradation Products using LCMS, Mass mediated Prep-HPLC, NMR and HRMS

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23189 ◽

2021 ◽

Vol 33 (6) ◽

pp. 1341-1350

Author(s):

K.V.K. Mohan Pulletikurthi ◽

S.S.K. Chakravarthy Kotha ◽

Raju Doddipalla ◽

Chidananda Swamy Rumalla ◽

Muralidharan Kaliyaperumal ◽

...

Keyword(s):

Mass Spectrometer ◽

Degradation Products ◽

Gradient Elution ◽

Stress Conditions ◽

Drug Degradation ◽

Ich Guidelines ◽

Oxidative Condition ◽

Stress Degradation ◽

The Stability

The stability of lacidipine drug under stress conditions and the identification of the degradation products, according to ICH guidelines Q1A (R2) were investigated in the hydrolytic and oxidative stress conditions. The drug degradation occurred under hydrolytic conditions like (acidic and basic) while it was stable in the oxidative condition. Three degradation products were formed under acidic condition and one degradation product was formed under basic condition, which was separated by using APMS (Auto Purification Mass Spectrometer) and gradient elution with C18 column. The four degradants have not been characterized earlier and in the present study all the structures were established and characterized using NMR spectroscopy (1D and 2D) and HRMS (high resolution mass spectrometer).

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Isolation and Structural Characterization of Degradation Products of Finasteride by Preparative HPLC, HRMS and 2D NMR

Asian Journal of Chemistry ◽

10.14233/ajchem.2019.21955 ◽

2019 ◽

Vol 31 (7) ◽

pp. 1514-1518

Author(s):

Santhosh Guduru ◽

V.V.S.R.N. Anji Karun Mutha ◽

B. Vijayabhaskar ◽

Muralidharan Kaliyaperumal ◽

Prabhakar S. Achanta ◽

...

Keyword(s):

Structural Characterization ◽

Degradation Products ◽

2D Nmr ◽

Preparative Hplc

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A Cytotoxic Natural Product from Patrinia villosa Juss

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190416101014 ◽

2019 ◽

Vol 19 (11) ◽

pp. 1399-1404 ◽

Cited By ~ 1

Author(s):

Yangcheng Liu ◽

Wei Liu ◽

Changlan Chen ◽

Zheng Xiang ◽

Hongwei Liu

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Silica Gel ◽

Column Chromatography ◽

Bioactive Compound ◽

Antitumor Agent ◽

2D Nmr ◽

Preparative Hplc ◽

Dependent Manner ◽

2D Nmr Spectra

Background and Purpose:: Patrinia villosa Juss is an important Chinese herbal medicine widely used for thousands of years, but few reports on the ingredients of the herb have been presented. In this study, we aim to isolate the bioactive compound from the plant. Material and Methods:: The air-dried leaves of P. villosa (15kg) were extracted three times with 70% EtOH under reflux. The condensed extract was suspended in H2O and partitioned with light petroleum, dichloromethane and n-BuOH. The dichloromethane portion was then subjected to normal-phase silica gel column chromatography, ODS silica gel column chromatography and semi-preparative HPLC to yield compound 1. Cytotoxicities of 1 were assayed on HepG2, A549 and A2780 cell lines. The mechanism of apoptosis and cell cycle on A549 was confirmed subsequently. Results: A new impecylone (Impecylone A) was isolated from the leaves of Patrinia villosa Juss, and its structures were established using 1D, 2D-NMR spectra and HR-ESI-MS. Impecylone A could selectivity inhibit HepG2 and A549 cell lines. The compound could induce apoptosis of A549 and arrest the cell cycle at G2/M phase in a dose-dependent manner. Conclusion: Impecylone A is a novel compound from Patrinia villosa Juss and could be a potential antitumor agent especially in the cell lines of A549.

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Characterization of stress degradation products of nintedanib by UPLC, UHPLC-Q-TOF/MS/MS and NMR: evidence of a degradation product with a structure alert for mutagenicity

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2021.114037 ◽

2021 ◽

pp. 114037

Author(s):

Vivek Dhiman ◽

Ankit Balhara ◽

Saranjit Singh ◽

Shristy Tiwari ◽

Samanthula Gananadhamu ◽

...

Keyword(s):

Degradation Product ◽

Degradation Products ◽

Stress Degradation ◽

Tof Ms

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IMPURITY PROFILING IMPURITY PROFILING OF THIAMINE HYDROCHLORIDE INJECTION BY RP-HPLC AND CHARACTERIZATION OF DEGRADATION PRODUCT BY LC-MS/MS/QTOF

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i6.38283 ◽

2020 ◽

pp. 151-161

Author(s):

SRINIVASU KONDRA ◽

BAPUJI A. T. ◽

D. GOWRI SANKAR ◽

POTTURI MURALI KRISHNAM RAJU

Keyword(s):

Degradation Product ◽

Degradation Products ◽

Hplc Method ◽

Thiamine Hydrochloride ◽

Injectable Formulation ◽

Hyphenated Technique ◽

Isolation And Characterization ◽

Impurity Profiling ◽

Rp Hplc

Objective: To propose a comprehensive, simple, and affordable RP-HPLC method for impurity profiling and characterization of unknown degradation products of thiamine hydrochloride injectable formulation. Methods: The chromatographic separation employs gradient mode using the octadecyl silane column using a mobile phase consisting of phosphate buffer with ion pair reagent, acetonitrile, and methanol delivered flow rate at 1.2 ml/min. The detection was carried out at 248 nm using empower software. LC-MS/MS/QTOF hyphenated technique was used for isolation and characterization of unknown degradation impurity. The performance of the method was systematically validated as per ICH Q2 (R1) guidelines. Results: Degradation product observed in accelerated stability was characterized by LC-MS/MS/QTOF hyphenated technique and found m/z value 351.1604 and postulated as an oxidative degradation product of thiamine due to excipient interaction. The validated method was sensitive, selective, and specific data proves the method is precise and accurate from LOQ to 150% level and results are within 95-108% and less than 4.5% RSD. The developed method is linear from 0.03-58.83 µg/ml with a correlation coefficient of more than 0.990 and LOD and LOQ value ranged from 0.03 to1.51 μg/ml. Conclusion: An efficient RP-HPLC method for impurity profiling of thiamine injectable formulation was successfully developed and unknown degradation product observed instability condition samples characterized by LC-MS/MS/QTOF technique. The validated method can be successfully employed for the impurity profiling of thiamine injectable in the quality control department.

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Development and Validation of a Novel Stability-Indicating Reversed-Phase Ion-Pair Chromatographic Method for the Quantitation of Impurities in Marbofloxacin Tablets

Journal of AOAC International ◽

10.5740/jaoacint.17-0108 ◽

2018 ◽

Vol 101 (4) ◽

pp. 1021-1029

Author(s):

Priyanka Maheshwari ◽

Neelima Shukla ◽

Manish Kumar Dare

Keyword(s):

Mobile Phase ◽

Chromatographic Method ◽

Degradation Products ◽

Reversed Phase ◽

Ion Pair ◽

Stress Conditions ◽

Main Peak ◽

Stability Indicating ◽

Photolytic Degradation ◽

The Stability

Abstract A stability-indicating isocratic reversed-phase ion-pair chromatographic method was designed for the separation of impurities in the presence of degradation products. Marbofloxacin tablets and a placebo were exposed to the stress conditions of oxidative, acid, base, humidity, thermal, and photolytic degradation. Significant and moderate degradation was observed in acidic and oxidative stress conditions, respectively. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating analytical method. The method was developed by using an XTerra RP18 3.5 μm (150 × 4.6 mm) column, with the mobile phase containing a mixture of buffer (pH 2.5)–methanol–glacial acetic acid (77 + 23 + 0.5, v/v). The flow rate of the mobile phase was 1.2 mL/min, with a column oven temperature of 40°C and a detection wavelength of 315 nm. The proposed method met Veterinary International Conference on Harmonization requirements and was successfully used for impurity quantitation in marbofloxacin tablets.

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Chemometric outlier classification of 2D-NMR spectra to enable higher order structure characterization of protein therapeutics

Chemometrics and Intelligent Laboratory Systems ◽

10.1016/j.chemolab.2020.103973 ◽

2020 ◽

Vol 199 ◽

pp. 103973 ◽

Cited By ~ 1

Author(s):

David A. Sheen ◽

Vincent K. Shen ◽

Robert G. Brinson ◽

Luke W. Arbogast ◽

John P. Marino ◽

...

Keyword(s):

Nmr Spectra ◽

2D Nmr ◽

Higher Order ◽

Protein Therapeutics ◽

Structure Characterization ◽

Order Structure ◽

2D Nmr Spectra

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Identification and characterization of olanzapine degradation products under oxidative stress conditions

Acta Chromatographica ◽

10.1556/achrom.20.2008.1.7 ◽

2008 ◽

Vol 20 (1) ◽

pp. 81-93 ◽

Cited By ~ 21

Author(s):

S. Hiriyanna Hiriyanna ◽

K. Basavaiah ◽

P. Goud ◽

V. Dhayanithi ◽

K. Raju ◽

...

Keyword(s):

Oxidative Stress ◽

Degradation Products ◽

Stress Conditions ◽

Identification And Characterization

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On the Stability and Degradation Pathways of Venetoclax under Stress Conditions

Pharmaceutics ◽

10.3390/pharmaceutics12070639 ◽

2020 ◽

Vol 12 (7) ◽

pp. 639

Author(s):

Nina Žigart ◽

Martin Črnugelj ◽

Janez Ilaš ◽

Zdenko Časar

Keyword(s):

High Resolution Mass Spectrometry ◽

Degradation Products ◽

Single Agent ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Stress Conditions ◽

Forced Degradation ◽

Degradation Pathways ◽

Orally Bioavailable ◽

The Stability

Venetoclax is an orally bioavailable, B-cell lymphoma-2 (BCL-2) selective inhibitor, used for the treatment of various types of blood cancers, such as chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this study we investigated the degradation of venetoclax under various stress conditions including acidic, basic, oxidative, photolytic and thermolytic conditions. We isolated and identified six of its main degradation products produced in forced degradation studies. The structures of the isolated degradation products were determined by using nuclear magnetic resonance (NMR) spectroscopy, high resolution mass spectrometry (HRMS) and infrared (IR) spectroscopy. Additionally, one oxidation degradation product was identified with comparison to a commercially obtained venetoclax impurity. We proposed the key degradation pathways of venetoclax in solution. To the best of our knowledge, no structures of degradation products of venetoclax have been previously published. The study provides novel and primary knowledge of the stability characteristics of venetoclax under stress conditions. Venetoclax is currently the only BCL-2 protein inhibitor on the market. In addition to single agent treatment, it is effective in combinational therapy, so future drug development involving venetoclax can be expected. A better insight into the stability properties of the therapeutic can facilitate future studies involving venetoclax and aid in the search of new similar therapeutics.

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