scholarly journals Identification and Structure Elucidation of Forced Degradation Products of the Novel Propionic acid Derivative Loxoprofen: Development of Stability-Indicating Chromatographic Methods Validated as per ICH Guidelines

Author(s):  
Maya S. Eissa ◽  
Osama I. Abd El-Sattar
2020 ◽  
Vol 103 (4) ◽  
pp. 980-988
Author(s):  
Ghada AbdElHamid Sedik ◽  
Doha Mohamed Naguib ◽  
Fahima Morsy ◽  
Hala Elsayed Zaazaa

Abstract Background Imidocarb dipropionate (IMD) is an immunomodulator agent commonly used for treatment of anaplasmosis in cattle. Objective Thus, two sensitive, specific, and precise stability-indicating chromatographic methods have been developed, optimized, and validated for its determination in presence of its acid, alkaline, and oxidative stressed degradation products. Method The first method is based on separation of IMD and its forced induced degradation products on reversed phase cyano column using isocratic elution system consisted of sodium acetate buffer–methanol–acetonitrile (55: 30:15, v/v/v), pH 4.6 at a flow rate of 1.2 mL/min, and UV detection at 254 nm. The second method utilized TLC combined with densitometric determination of the separated bands at 254 nm. The separation was achieved using silica gel 60 F254 TLC plates with a mixture of ethyl acetate–methanol–ammonia–water (8.5:1:0.5:0.2, v/v/v/v) as a developing system. Results HPLC analysis was applied in range of 0.25–40 µg/mL with LOD of 0.073 µg/mL. While densitometric measurements showed linearity in the range of 0.1–1.8 µg/band with LOD of 0.02 µg/band. Conclusions The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of IMD in its commercial veterinary formulations with good recoveries. Furthermore, the proposed HPLC method was extended to the determination of IMD residues in bovine meat and milk samples Highlights Bovine meat, HPLC, Imidocarb dipropionate, Milk, TLC.


Author(s):  
M. Rizk ◽  
S. Toubar ◽  
E. Ramzy ◽  
Marwa Helmy

AbstractNew, sensitive, rapid, cost-effective, and validated stability-indicating thin layer chromatographic (TLC) method coupled with fluorescence (FL) detection was developed for the quantitative analysis of celecoxib (CEL) and amlodipine besylate (AMLO) in their laboratory prepared binary mixture using the non-fluorescent TLC silica gel 60 plates. Ethyl acetate: diethylamine: 1-propanol (9:1:0.2, V/V) was used as a developing system. The retention factor (Rf) for each drug was 0.80 ± 0.03 and 0.44 ± 0.01 for CEL and AMLO, respectively. The plates were excited at 264 nm for the simultaneous FL measurement of CEL and AMLO, the calibration curves were linear over a concentration ranges of 30.0–300.0 ng/band and 15.0–150.0 ng/band with mean percentage recoveries of 99.80 ± 0.85 and 99.80 ± 0.77 For CEL and AMLO, respectively. The developed method was applied for the stability studies of the cited drugs in their laboratory prepared binary mixture and the forced degradation products were determined when present in presence of the pure drugs so the method can be considered as a stability-indicating one and it was validated as per ICH guidelines and proved to be accurate and precise.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Josilene Chaves Ruela Corrêa ◽  
Cristina Helena dos Reis Serra ◽  
Hérida Regina Nunes Salgado

Chemical and physical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the aim of this work was to study the stability of darunavir and to develop and validate a liquid chromatography (LC) method to determine darunavir in raw material and tablets in the presence of degradation products. The novel method showed to be linear from 6.0 to 21.0 μg/mL, with high precision (CV < 2%) and accuracy (recuperation of 99.64%). It is simple and reliable, free of placebo interferences. The robustness of the method was evaluated by a factorial design using seven different parameters. Forced degradation study was done under alkaline, acidic, and oxidative stress at ambient temperature and by heating. The LC method was able to quantify and separate darunavir and its degradation products. Darunavir showed to be unstable under alkaline, acid, and oxidative conditions. The novelty of this study is understanding the factors that affect darunavir ethanolate stability in tablets, which is the first step to unravel the path to know the degradation products. The novel stability-indicating method can be used to monitor the drug and the main degradation products in low concentrations in which there is linearity.


2021 ◽  
Vol 12 (4) ◽  
pp. 2485-2491
Author(s):  
Nageswara Rao Jakkam ◽  
Sudhakar Chintakula ◽  
Sreenivasa Rao Battula

In order to develop a stability regulatory system for drug substances and degraded products, a forced degradation study is an essential part in the design of the method. As per ICH Guidelines Q1A in 1993, it was established as an essential requirement for the regulatory system to assess the stability of drugs and their degradation products under the degradation studies by force. These analytical methods are helpful in the development of stability, indicating the method by conducting the studies on forced degradation with their mechanism of degradation. Drug products by degradation and new drug substance by forced degradation conditions are more severe than a demonstration of specificity of stability indicating methods. The analytical method development is facilitated by those techniques for better understanding of (API) active pharmaceutical ingredients and (DP) drug products stability.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ramakrishna Kommana ◽  
Praveen Basappa

The present paper describes the development of quick stability indicating RP-HPLC method for the simultaneous estimation of codeine phosphate and chlorpheniramine maleate in the presence of its degradation products, generated from forced degradation studies. The developed method separates codeine phosphate and chlorpheniramine maleate in impurities/degradation products. Codeine phosphate and chlorpheniramine maleate and their combination drug product were exposed to acid, base, oxidation, dry heat, and photolytic stress conditions, and the stressed samples were analysed by proposed method. The proposed HPLC method utilizes the Shimadzu HPLC system on a Phenomenex C18 column (, 5 μ) using a mixture of 1% o-phosphoric acid in water : acetonitrile : methanol (78 : 10 : 12) mobile phase with pH adjusted to 3.0 in an isocratic elution mode at a flow rate of 1 mL/min, at 23°C with a load of 20 μL. The detection was carried out at 254 nm. The retention time of codeine phosphate and chlorpheniramine maleate was found to be around 3.47 min and 9.45 min, respectively. The method has been validated with respect to linearity, robustness, precision, accuracy, limit of detection (LOD), and limit of quantification (LOQ). The developed validated stability indicating HPLC method was found to be simple, accurate, and reproducible for the determination of instability of these drugs in bulk and commercial products.


2018 ◽  
Vol 3 (4) ◽  
pp. 207-218 ◽  
Author(s):  
Mouloud Yessaad ◽  
Lise Bernard ◽  
Daniel Bourdeaux ◽  
Philip Chennell ◽  
Valérie Sautou

Abstract Background Water-soluble vitamins are often included simultaneously in pharmaceutical formulations as food complements or in parenteral nutrition mixtures. Given their sensitivity to heat, light or pH variations, it is important to study their stability using validated stability indicating methods. We thus aimed to validate a liquid chromatography (LC) stability-indicating method for the simultaneous quantification of 5 water-soluble vitamins. Methods We analyzed four water-soluble B vitamins (nicotinamide, pyridoxine, folic acid, cyanocobalamin) and ascorbic acid using a LC method with diode array detector. They were separated on a C18 stationary phase under gradient elution of solvent A [0.2 % of metaphosphoric acid in water and acetonitrile 98:2] and solvent B (100 % acetonitrile). All vitamins were subjected to forced degradation conditions and we showed that the obtained degradation products didn’t interfere with the vitamins. Results The method allows the separation of the 5 water-soluble vitamins in a 30 minute run without any interference from the breakdown products obtained with acid/alkaline solutions, hydrogen peroxide, temperature and light. It meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity. Conclusions This stability-indicating method can be used for carrying out stability studies of water-soluble vitamins in pharmaceutical preparations.


Author(s):  
Birva A. Athavia ◽  
Zarna R. Dedania ◽  
Ronak R. Dedania ◽  
S. M. Vijayendra Swamy ◽  
Chetana B. Prajapati

Objective: The aim and objective of this study was to develop and validate Stability Indicating HPLC method for determination of Vilazodone Hydrochloride.Methods: The method was carried out on a Phenomenex, C18 (250x4.6 mm, 5 µm) Column using a mixture of Acetonitrile: Water (50:50v/v), pH adjusted to 3.3 with Glacial Acetic Acid for separation. The flow rate was adjusted at 1 ml/min and Detection was carried out at 240 nm.Results: The retention time of vilazodone hydrochloride was found to be 2.3 min. The calibration curve was found to be linear in the range 25-75µg/ml with a correlation coefficient (R2=0.996). The limit of detection and limit of quantitation were found to be 4.78µg/ml and 14.48µg/ml respectively. The % recovery of vilazodone hydrochloride was found to be in the range of 98.21±0.08 % to 99.07±0.64%. The proposed method was successfully applied for the estimation of vilazodone hydrochloride in marketed tablet formulation.Vilazodone Hydrochloride was subjected to forced degradation under Acidic, Alkaline, Oxidation, Dry Heat and Photolytic degradation conditions. Vilazodone hydrochloride showed 3.12% degradation under acidic condition, 4.78% under alkaline condition, 7.8% under oxidation condition, 3.53% under dry heat condition and 4.9% under photolytic condition.Acid degradation impurity was identified and characterised by LC-MS/MS was found to be 1-(4-Penten-1-yl) piperazine having molecular weight 154.253 (m/z 155.08) and Molecular Formula C9H18N2.Conclusion: A simple, precise, rapid and accurate Stability Indicating HPLC method has been developed and validated for the determination of Vilazodone Hydrochloride in presence of its degradation products as per the ICH Guidelines. 


Author(s):  
Ramreddy Godela ◽  
Sowjanya G

A trouble-free, simple, specific and highly sensitive stability indicating phase HPLC method was developed for concurrent assessment of Daclatasvir and Sofosbuvir in pure and in their combined tablet formulation. An effectual separation was accomplished by using XDB Phenyl (250 x 4.6mm, 5µ,100 A0) column, mobile phase composition of Acetonitrile: buffer(0.1%v/v Trifluoroaceticacid in water) (50:50 v/v) and isocratic elution at a flow rate of 1ml/min and detection wavelength of 275nm. The extreme stress conditions like hydrolysis with acid and base, peroxide oxidation, thermal decomposition were used as per ICH specifications to assess the stability of the analytes in bulk and dosage forms. The retention times of Daclatasvir and Sofosbuvir were found at 2.8 and 3.7min respectively. The proposed method has linear response in the concentration ranges from 12 to 36µg/ml and 80 to 240 µg/ml for Daclatasvir and Sofosbuvir respectively. The detection and quantification limits calculated as 2.5μg/ml and 7.8μg/ml for DCL, 5.2μg/ml and 15.8μg/ml SOF respectively. All the method validation parameters were met the acceptance limits of Q2 specifications of ICH procedures. The degradation products produced by forced degradation studies were have good resolution from Daclatasir and Sofosbuvir peaks, which represents the methods stability. The proposed RP-HPLC method was highly sensitive, precise, stability indicating and economical. That’s why the method has the capacity to employ in the pharmaceutical manufacturing of Daclatasvir and Sofosbuvir and routine analysis in quality control department.


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