Identification and structural characterization of the stress degradation products of omeprazole using Q-TOF-LC-ESI-MS/MS and NMR experiments: evaluation of the toxicity of the degradation products

2019 ◽  
Vol 43 (19) ◽  
pp. 7294-7306 ◽  
Author(s):  
G. Shankar ◽  
Roshan M. Borkar ◽  
Suresh Udutha ◽  
M. Kanakaraju ◽  
G. Sai Charan ◽  
...  
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Proton Pump Inhibitor ◽  
Gastroesophageal Reflux ◽  
Degradation Products ◽  
Forced Degradation ◽  
Peptic Ulcers ◽  
Ich Guidelines ◽  
Stress Degradation ◽  
Forced Degradation Studies

Omeprazole (OMP), a prototype proton pump inhibitor used for the treatment of peptic ulcers and gastroesophageal reflux disease (GERD), was subjected to forced degradation studies as per ICH guidelines Q1A (R2).

scholarly journals LC-MS/MS CHARACTERIZATION OF FORCED DEGRADATION PRODUCTS OF TUCATINIB, A NOVEL TYROSINE KINASE INHIBITOR: DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD

2022 ◽  
pp. 58-66
Author(s):  
S. K. REEHANA ◽  
K. SUJANA
Keyword(s):  
Kinase Inhibitor ◽  
Degradation Products ◽  
Degradation Pathway ◽  
Hplc Method ◽  
Forced Degradation ◽  
Ich Guidelines ◽  
System Suitability ◽  
Forced Degradation Studies ◽  
Development And Validation

Objective: The current study focused on the development, validation, and characterization of forced degradation products using LC-MS/MS. Methods: A simple, selective, validated and well-defined isocratic HPLC methodology for the quantitative determination of Tucatinib at a wavelength of 239 nm. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6 mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 ml/min. MS/MS was used to characterize degradation products formed in the forced degradation study. The validation and characterization of forced degradation products were performed in accordance with ICH guidelines. Results: Over the concentration range of 5-100μg/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. According to standard guidelines, the method was quantitatively evaluated in terms of system suitability, linearity, precision, accuracy, and robustness, and the results were found to be within acceptable limits. The drug was degraded under acidic, alkaline, and reduction conditions in forced degradation studies. Conclusion: The method was found to be applicable for routine tucatinib analysis. Because no LC-MS/MS method for estimating tucatinib and its degradation products has been reported in the literature. There is a need to develop a method for studying the entire tucatinib degradation pathway.

Characterization of stress degradation products of blonanserin by UPLC-QTOF-tandem mass spectrometry

RSC Advances ◽  
2015 ◽  
Vol 5 (85) ◽  
pp. 69273-69288 ◽  
Author(s):  
Pradipbhai D. Kalariya ◽  
Prinesh N. Patel ◽  
Mahesh Sharma ◽  
Prabha Garg ◽  
R. Srinivas ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Tandem Mass Spectrometry ◽  
Degradation Products ◽  
Structural Elucidation ◽  
Forced Degradation ◽  
Tandem Mass ◽  
Degradation Study ◽  
Stress Degradation

Forced degradation study of blonanserin and structural elucidation of its degradation products was performed using high resolution tandem mass spectrometry.

Characterization of the degradation products of bambuterol using LCMS-QTOF and NMR

2015 ◽  
Vol 7 (18) ◽  
pp. 7659-7673 ◽  
Author(s):  
A. Abiramasundari ◽  
V. Sudarsanam ◽  
Kamala K. Vasu
Keyword(s):  
Degradation Products ◽  
Forced Degradation ◽  
Degradation Study ◽  
Ich Guidelines ◽  
Mechanisms Of Formation

A systematic forced degradation study of bambuterol was carried out according to ICH guidelines. Twelve degradation products of bambuterol were identified and characterized. Plausible mechanisms of formation of the degradation products are discussed.

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

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).

scholarly journals Isolation, Identification and Characterization of Gefitinib Novel Degradation Products by NMR and HRMS, Method Development and Validation by UPLC

2021 ◽  
Vol 33 (8) ◽  
pp. 1743-1748
Author(s):  
Ramulu Yanaka ◽  
Hima Bindu Gandham ◽  
Chidananda Swamy Rumalla ◽  
Muralidharan Kaliyaperumal ◽  
Shaik John Saida ◽  
...  
Keyword(s):  
Method Development ◽  
Degradation Products ◽  
2D Nmr ◽  
The Novel ◽  
Ich Guidelines ◽  
Stress Degradation ◽  
Method Development And Validation ◽  
Development And Validation ◽  
Identification And Characterization

Gefitinib (GFT) sold under the brand name Iressa, is a medication used to treat certain type of breast, lung and other cancers, Gefitinib was subject to stress degradation under acidic, basic, peroxide mediated oxidation, photolytic and thermal degradation. The stress degradation was performed according to ICH guidelines Q1A(R2) and the drug was inert under thermal and photolytic conditions. One degradant is identified in acid hydrolysis referred as 7-methoxy-6-(3-morpholinopropoxy) quinazolin-4(3H)-one (GFT-DP1) and two degradants were formed in peroxide mediated hydrolysis referred as 4-(3-((4-((3- chloro-4-fluorophenyl)amino)-7-methoxy-1-oxidoquinazolin-6-yl)oxy)-propyl)morpholine-4-oxide (GFT-DP2) and 4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)-propyl)- morpholine-4-oxide (GFT-DP3). In present study, all the novel three degradation product structures were confirmed by HRMS and 1D (1H, 13C) and 2D (COSY, HSQC and HMBC) based on 1D and 2D NMR data proton and carbon chemical shift values assigned exactly for all degradation products. A stability indicating RP-UPLC method was developed and validated with shorter run time and this method was validated in terms of linearity, specificity, accuracy, LOD and LOQ.

scholarly journals Chemical characterization of the photodegradation products of midazolam complexes with randomly methylated-β-cyclodextrin by HPLC and LC-MS/MS

2016 ◽  
Vol 81 (9) ◽  
pp. 1037-1053 ◽  
Author(s):  
Snezana Agatonovic-Kustrin ◽  
Mosimotsana Lebete ◽  
Michael Brown ◽  
David Morton ◽  
Beverley Glass
Keyword(s):  
Degradation Products ◽  
Degradation Mechanism ◽  
Chemical Characterization ◽  
Aqueous Solubility ◽  
Forced Degradation ◽  
Intermediate Structure ◽  
Forced Degradation Studies ◽  
Photodegradation Products ◽  
Methylated Cyclodextrin

Midazolam, a potent anxiolytic drug with sedative properties, is susceptible to degradation by both light and hydrolysis in aqueous solution. When formulated as an intranasal product it was found to be effective in achieving seizure control in epileptic patients. In order to deliver an adequate therapeutic dose to a patient, a nasal formulation requires the concentration of midazolam to be higher than its? aqueous solubility. One way to increase midazolam solubility to a therapeutic concentration, is complexation with randomly methylated-?-cyclodextrin. Thus, it is important to determine how complexation with cyclodextrin affects the rate of degradation and type of midazolam degradants that are formed. We have found that complexation with cyclodextrin decreases its photostability. More importantly, the degradation profile for midazolam is significantly altered when it is complexed with randomly methylated-?-cyclodextrin, what we partly confirmed in our previous work.1 By continuing our study we have found that degradation products, not observed on the photodegradation of uncomplexed midazolam are observed in significant quantities when it is complexed with randomly methylated-?-cyclodextrin. The decreased photostability was accompanied by the appearance of two new degradation products, an intermediate structure and a dimer. Photoproduct formation followed the same pattern as in the forced degradation studies, further confirming the presence of an intermediate. The production of these new photodegradants, characterized with their MS spectra, as well as proposed degradation mechanism of midazolam is discussed.

Characterization of the stress degradation products of tolvaptan by UPLC-Q-TOF-MS/MS

RSC Advances ◽  
2015 ◽  
Vol 5 (27) ◽  
pp. 21142-21152 ◽  
Author(s):  
Prinesh N. Patel ◽  
D. Rajesh Kumar ◽  
S. Gananadhamu ◽  
R. Srinivas
Keyword(s):  
Degradation Products ◽  
Forced Degradation ◽  
Dry Heat ◽  
Stress Degradation ◽  
Tof Ms

TVT was subjected to forced degradation under hydrolysis, oxidation, dry heat and photolysis conditions and the degradation products (DPs) formed have been characterized through UPLC-PDA and UPLC-Q-TOF-MS/MS studies.

scholarly journals Chemometrics Approaches in Forced Degradation Studies of Pharmaceutical Drugs

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3804
Author(s):  
Benedito Roberto de Alvarenga Junior ◽  
Renato Lajarim Carneiro
Keyword(s):  
Degradation Products ◽  
Drug Product ◽  
Forced Degradation ◽  
Pharmaceutical Drugs ◽  
Know How ◽  
Pharmaceutical Ingredients ◽  
Physicochemical Stability ◽  
Forced Degradation Studies ◽  
Degradation Studies

Chemometrics is the chemistry field responsible for planning and extracting the maximum of information of experiments from chemical data using mathematical tools (linear algebra, statistics, and so on). Active pharmaceutical ingredients (APIs) can form impurities when exposed to excipients or environmental variables such as light, high temperatures, acidic or basic conditions, humidity, and oxidative environment. By considering that these impurities can affect the safety and efficacy of the drug product, it is necessary to know how these impurities are yielded and to establish the pathway of their formation. In this context, forced degradation studies of pharmaceutical drugs have been used for the characterization of physicochemical stability of APIs. These studies are also essential in the validation of analytical methodologies, in order to prove the selectivity of methods for the API and its impurities and to create strategies to avoid the formation of degradation products. This review aims to demonstrate how forced degradation studies have been actually performed and the applications of chemometric tools in related studies. Some papers are going to be discussed to exemplify the chemometric applications in forced degradation studies.

Sign in / Sign up

Export Citation Format

Share Document