scholarly journals Identification of Crizotinib Major Degradation Products Obtained Under Stress Conditions by RP-UHPLC-HRMS

2021 ◽  
Vol 94 (1) ◽  
Author(s):  
Kristina Tolić ◽  
Mislav Runje ◽  
Tatjana Gazivoda Kraljević ◽  
Dragana Mutavdžić Pavlović
Keyword(s):  
Degradation Products ◽  
Stress Conditions

scholarly journals Comparison of Three Complementary Analytical Techniques for the Evaluation of the Biosimilar Comparability of a Monoclonal Antibody and an Fc-Fusion Protein

2021 ◽  
Vol 9 ◽  
Author(s):  
Alice Demelenne ◽  
Arij Ben Yahia ◽  
Delphine Lempereur ◽  
Jacques Crommen ◽  
Anne-Catherine Servais ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Fusion Protein ◽  
Method Development ◽  
Reference Product ◽  
Degradation Products ◽  
Stress Conditions ◽  
Size Exclusion ◽  
Mild Stress ◽  
Molecular Weight Determination ◽  
Fc Fusion Protein

In this work, a monoclonal antibody, adalimumab, and an Fc-fusion protein, etanercept, were studied and compared to one of their biosimilars. Samples submitted to stress conditions (agitation and high temperature) were used for method development. The developed methods were also applied to samples reduced by beta-mercaptoethanol to evaluate their capability to distinguish the expected species. Capillary gel electrophoresis (CGE), reversed-phase liquid chromatography (RPLC), and size-exclusion chromatography (SEC) methods coupled with UV detection were used to analyze the biopharmaceuticals. Their complementarity was investigated. For further molecular weight determination, SEC-multi angle light scattering and RPLC-quadrupole time-of-flight were occasionally used. For adalimumab, a larger amount of fragments and aggregates was observed in the biosimilar compared with the reference product. For etanercept, more related species were found in the reference product. Those three separation techniques showed good complementarity. Indeed, RPLC enabled the separation of hydrophilic and hydrophobic degradation products. CGE provided good selectivity for several adalimumab fragments, and SEC was useful for the analysis of aggregates and certain fragments that cannot be separated by the other approaches. Moreover, those formulations were submitted to mild stress conditions (30°C, 300 rpm for 4 h) that mimic shipping conditions. No additional peak was found under these conditions for the two studied biopharmaceuticals.

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

2019 ◽  
Vol 31 (4) ◽  
pp. 851-854
Author(s):  
Santhosh Guduru ◽  
V.V.S.R.N. Anji Karun Mutha ◽  
B. Vijayabhaskar ◽  
Muralidharan Kaliyaperumal ◽  
Raghu Babu Korupolu ◽  
...  
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Acid Stress ◽  
2D Nmr ◽  
Stress Conditions ◽  
Preparative Hplc ◽  
Mass Spectral ◽  
2D Nmr Spectra ◽  
The Stability

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.

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

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.

Identification and characterization of olanzapine degradation products under oxidative stress conditions

2008 ◽  
Vol 20 (1) ◽  
pp. 81-93 ◽  
Author(s):  
S. Hiriyanna Hiriyanna ◽  
K. Basavaiah ◽  
P. Goud ◽  
V. Dhayanithi ◽  
K. Raju ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Degradation Products ◽  
Stress Conditions ◽  
Identification And Characterization

scholarly journals On the Stability and Degradation Pathways of Venetoclax under Stress Conditions

Pharmaceutics ◽  
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.

scholarly journals Development and Validation of a Stability-Indicating RP-HPLC Method for Determination of Atomoxetine Hydrochloride in Tablets

2010 ◽  
Vol 93 (4) ◽  
pp. 1207-1214 ◽  
Author(s):  
Sejal K Patel ◽  
Natvarlal J Patel
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Stress Conditions ◽  
Acid Base ◽  
Photodiode Array Detection ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Rp Hplc ◽  
Wet Heat

Abstract This paper describes the development of a stability-indicating RP-HPLC method for the determination of atomoxetine hydrochloride (ATX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. In stability tests, the drug was susceptible to acid, base, oxidation, and dry and wet heat degradation. It was found to be stable under the photolytic conditions tested. The drug was successfully separated from the degradation products formed under stress conditions on a Phenomenex C18 column (250 4.6 mm id, 5 m particle size) by using acetonitrilemethanol0.032 M ammonium acetate (55 + 05 + 40, v/v/v) as the mobile phase at 1.0 mL/min and 40C. Photodiode array detection at 275 nm was used for quantitation after RP-HPLC over the concentration range of 0.55 g/mL with a mean recovery of 100.8 0.4 for ATX. Statistical analysis demonstrated that the method is repeatable, specific, and accurate for the estimation of ATX. Because the method effectively separates the drug from its degradation products, it can be used as a stability-indicating method.

scholarly journals Validated Reverse Phase HPLC Method for the Determination of Impurities in Etoricoxib

2011 ◽  
Vol 8 (s1) ◽  
pp. S119-S126
Author(s):  
S. Venugopal ◽  
U. M. Tripathi ◽  
N. Devanna
Keyword(s):  
Degradation Products ◽  
Sodium Hydroxide Solution ◽  
Hplc Method ◽  
Stress Conditions ◽  
Forced Degradation ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Successful Separation ◽  
Forced Degradation Studies

This paper describes the development of reverse phase HPLC method for etoricoxib in the presence of impurities and degradation products generated from the forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of etoricoxib was observed under base and oxidation environment. The drug was found stable in other stress conditions studied. Successful separation of the drug from the process related impurities and degradation products were achieved on zorbax SB CN (250 x 4.6 mm) 5 μm particle size column using reverse phase HPLC method. The isocratic method employed with a mixture of buffer and acetonitrile in a ratio of 60:40 respectively. Disodium hydrogen orthophosphate (0.02 M) is used as buffer and pH adjusted to 7.20 with 1 N sodium hydroxide solution. The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness.

Separation, Identification, and Characterization of Degradation Products of Erlotinib Hydrochloride Under ICH-Recommended Stress Conditions by LC, LC-MS/TOF

2014 ◽  
Vol 38 (5) ◽  
pp. 629-639 ◽  
Author(s):  
Anand A. Mahajan ◽  
Pankaj B. Miniyar ◽  
Amol S. Patil ◽  
Rohan U. Waghmare ◽  
Jayawant J. Patil ◽  
...  
Keyword(s):  
Degradation Products ◽  
Stress Conditions ◽  
Identification And Characterization
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