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.

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.

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.

Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

2020 ◽  
Vol 16 (8) ◽  
pp. 1130-1139
Author(s):  
Singaram Sathiyanarayanan ◽  
Chidambaram Subramanian Venkatesan ◽  
Senthamaraikannan Kabilan
Keyword(s):  
Mass Spectra ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
A2a Adenosine Receptor ◽  
Degradation Study ◽  
Related Substances ◽  
Adenosine Receptor Agonist

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents. Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis. Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier. Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

LC-MS/MS method for the characterization of the forced degradation products of Entecavir

2014 ◽  
Vol 37 (4) ◽  
pp. 368-375 ◽  
Author(s):  
Thippani Ramesh ◽  
Pothuraju Nageswara Rao ◽  
Ramisetti Nageswara Rao
Keyword(s):  
Degradation Products ◽  
Forced Degradation

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

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.

Sign in / Sign up

Export Citation Format

Share Document