Analytical Method Development and Validation for the Analysis of Nepafenac and its related substances using Ultra Performance Liquid Chromatography

2021 ◽  
pp. 4178-4184
Author(s):  
T. S. Balaji ◽  
Gavaskar. D ◽  
Somanathan T.
Keyword(s):  
Analytical Method ◽  
Method Development ◽  
Degradation Products ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Base Hydrolysis ◽  
Forced Degradation ◽  
Equilibration Time ◽  
Elution Time ◽  
Related Substances

A novel, economic and time-efficient reverse-phase ultra-performance liquid chromatographic (RP-UPLC) method has been developed for the analysis of Nepafenac in the presence of both impurities and degradation products generated by forced degradation. When Nepafenac was subjected to acid hydrolysis, oxidative, base hydrolysis, photolytic, and thermal stress, observed degradation only in oxidative and base hydrolysis. The drug was found to be stable to other stress conditions. Various method development trails were performed for the separation of drug from impurities. However, best chromatographic separation was achieved on a Waters Acquity CSHC18, 100mm x 2.1mm, 1.7µ particle size column, UV detection at 245nm, a gradient elution of Ammonium formate (pH 4.0), mixture of organic solvents (Acetonitrile, Methanol) as mobile phase for drug, its impurities and it was captured. The method was validated for specificity, precision, linearity, accuracy, robustness and can be used in quality control during manufacture and for assessment of the stability samples of Nepafenac. Total elution time was about 6.5 min and equilibration time of about 1.5 min which allowed analysis of more than 100 samples per day. The analytical method discussed in United states Pharmacopoeia was pH sensitive and compatible to LC-MS analysis.

Analytical Method Development and Validation for the Analysis of Donepezil Hydrochloride and Its Related Substances Using Ultra Perfomance Liquid Chromatography

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Mahalingam V. ◽  
Kalaivani V. ◽  
Somanathan T. ◽  
Vijayabaskar S.
Keyword(s):  
Analytical Method ◽  
Method Development ◽  
Degradation Products ◽  
Gradient Elution ◽  
Stress Conditions ◽  
Base Hydrolysis ◽  
Forced Degradation ◽  
Equilibration Time ◽  
Elution Time ◽  
Donepezil Hydrochloride

A novel, economic and time-efficient reverse-phase ultra-performance liquid chromatographic (RP-UPLC) method has been developed for the analysis of Donepezil hydrochloride in the presence of both impurities and degradation products generated by forced degradation. When Donepezil hydrochloride was subjected to acid hydrolysis, oxidative, base hydrolysis, photolytic, and thermal stress, degradation was observed only in oxidative and base hydrolysis. The drug was found to be stable to other stress conditions. Successful chromatographic separation of the drug from impurities formed during synthesis and from degradation products formed under stress conditions was achieved on a Waters Acquity C18, 50 mm x 2.1mm, 1.7µ particle size column, UV detection at 286nm and a gradient elution of Trifluoroacetic acid, Acetonitrile and methanol as mobile phase. The method was validated for specificity, precision, linearity, accuracy, robustness and can be used in quality control during manufacture and for assessment of the stability samples of Donepezil hydrochloride. Total elution time was about 6 min and equilibration time of about 2 min which allowed analysis of more than 100 samples per day. The analytical method discussed in British Pharmacopeia was pH sensitive and not compatible to LC-MS analysis but the method reported in this study is more compatible to LC-MS which will be more suitable to perform LC-MS.

scholarly journals Determination of Mesalamine Related Impurities from Drug Product by Reversed Phase Validated UPLC Method

2011 ◽  
Vol 8 (1) ◽  
pp. 131-148 ◽  
Author(s):  
Trivedi Rakshit Kanubhai ◽  
Patel Mukesh C ◽  
Kharkar Amit R
Keyword(s):  
Degradation Products ◽  
Drug Product ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Release Formulation ◽  
Delayed Release ◽  
Related Substances

In the present study gradient reversed-phase UPLC method was developed for simultaneous determination and separation of impurities and degradation products from drug product. The chromatographic separation was performed on acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm) using gradient elution. Other UPLC parameters which were optimised are flow rate, 0.7 mL/min; detection wavelength, 220 nm; column oven temperature, 40°C and injection volume 7 µL. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated as per International Conference on Harmonization (ICH) guideline. For all impurities and mesalamine, LOQ (limit of quantification) value was found precise with RSD (related standard daviation) of less than 2.0%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was successfully applied for quantification of impurities and degradation products in mesalamine delayed-release formulation. The same method can also be used for determination of related substances from mesalamine drug substance.

scholarly journals ANALYTICAL METHOD DEVELOPMENT AND VALIDATION STUDIES OF TICAGRELOR TABLETS BY RP-HPLC

2017 ◽  
Vol 9 (4) ◽  
pp. 10 ◽  
Author(s):  
K. Tabassum ◽  
R. Sarvesh
Keyword(s):  
Analytical Method ◽  
Validation Studies ◽  
Method Development ◽  
Forced Degradation ◽  
Modified Method ◽  
Related Substances ◽  
Rp Hplc ◽  
Ich Guidelines ◽  
Method Development And Validation ◽  
Development And Validation

Objective: The present study was conducted to develop a simple and precise analytical method for the estimation of ticagrelor in tablet formulation.Methods: Reverse Phase HPLC was used for method development and validation studies of ticagrelor. The optimum chromatographic conditions comprised of C18 column (Kromasil, 250×4.6 mm, 5 µ) as the stationary phase and aqueous buffer (containing 0.5 ml formic acid and triethylamine each in water) and acetonitrile in the ratio of 50:50 v/v as the mobile phase. The flow rate was 1.3 ml/min with detection at 256 nm and a run time of 6 min. Forced degradation studies were conducted and the isocratic mode was modified to a gradient mode to make the method stability indicating in nature.Results: The retention time of ticagrelor was 3.372 min. The linearity studies indicated that the range of the developed method was 20-90 ppm with a correlation coefficient of 0.9956. The method was specific with a percent mean recovery was found to be 99.93%.. The % RSD in the precision studies was 0.069. The validated method was applied to conduct the assay of ticagrelor in tablets and the with a percent mean recovery of 99.82%. The modified method was capable of resolving 13 related substances from the ticagrelor peak in the forced degradation studies.Conclusion: The developed and validated RP-HPLC isocratic method was simple, accurate and precise as per the ICH guidelines. It was suitable for the analysis of ticagrelor in bulk and tablet formulation. The modified gradient method can be used to resolve the in-process impurities and related substances and can be directly applied to liquid chromatography hyphenated with mass spectroscopy (LC/MS) studies with minor modifications for identification of related substances.

scholarly journals SIMULTANEOUS REVERSE-PHASE ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT AND VALIDATION FOR ESTIMATION OF GRAZOPREVIR AND ELBASVIR

2018 ◽  
Vol 11 (4) ◽  
pp. 100
Author(s):  
Madhavi S ◽  
Prameela Rani A
Keyword(s):  
Liquid Chromatography ◽  
Method Development ◽  
Degradation Products ◽  
Ultra Performance Liquid Chromatography ◽  
Main Peak ◽  
Forced Degradation ◽  
Reverse Phase ◽  
Stability Indicating ◽  
Short Period ◽  
The Stability

 Objective: The objective of this study was to develop and validate rapid, specific, sensitive, and precise reverse-phase ultra performance liquid chromatography (RP-UPLC) method for the quantitative determination of grazoprevir and elbasvir, as there are no official monograph and no analytical method by UPLC.Methods: Chromatographic separation was achieved on a Waters Acquity UPLC HSS C18 (2.1 mm × 100 mm, 1.8 micron) column with a 45:55 (v/v) mixture of 0.1% orthophosphoric acid (pH 2.8) and acetonitrile as a mobile phase, thermostated at 30°C with a short run time of 3.0 min.Results: The retention times were 0.73 and 1.29 min for grazoprevir and elbasvir, respectively. Quantification is achieved with TUV detection at 254 nm over the concentration range of 25–150 μg/ml for grazoprevir and for elbasvir 12.5–75 μg/ml, with a correlation coefficient of 0.999 and 0.999, respectively. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity, and robustness. Forced degradation study was extended out under acidic, alkaline, oxidative, photolytic, and thermal conditions to demonstrate the stability-indicating capability of the developed UPLC method. The degradation products were well resolved from the main peak, thus proved the stability-indicating power of the method. The results of the analysis were validated statistically.Conclusion: The method is precise, accurate, linear, robust, and fast. The short retention time allows the analysis of a large number of samples in a short period of time and, therefore, should be cost-effective for routine analysis in the pharmaceutical industry.

Simultaneous Determination of Methocarbamol and Paracetamol in the Presence of Three Related Substances by Ultra Performance Liquid Chromatography

2019 ◽  
Vol 15 (5) ◽  
pp. 505-510
Author(s):  
Yanjuan Zheng ◽  
Qiushi Peng ◽  
Rui Dong ◽  
Tingyu Chen ◽  
Yi Bao ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Pharmaceutical Preparations ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Related Substances ◽  
Bulk Powder ◽  
Highly Sensitive ◽  
Optimal Protocol ◽  
Acquity Uplc

Introduction: A rapid, and accurate Ultra Performance Liquid Chromatography (UPLC) method was developed to simultaneously analyze Methocarbamol, Paracetamol and the related substances Materials and Methods: Waters ACQUITY UPLC® BEH Phenyl C18 column was used in conjunction with UV detection at 225nm. Gradient elution with 0.05M, pH 6 phosphate buffer and acetonitrile flow at 0.3mL /min rate were used to separate the substances. The retention times for 4-Aminopheno, Paracetamol, Guaifenesin, Methocarbamol, and 4-Chloroacetanilide were 1.319 minute, 2.224 minute, 4.467 minute, 4.769 minute and 5.433 minute respectively. The concentration was linear in the range of 2-100 µg/ml for Methocarbamol, and 1-100 µg/mL for Paracetamol. The percentage recoveries were between 99.28±1.23% to 100.57±0.99% for Methocarbamol, and between 99.08±1.23% to 101.23±1.39% for Paracetamol. Results and Discussion: The validated optimal protocol is robust and accurate for simultaneous analysis of Methocarbamol, Paracetamol and the related substances, applicable for bulk powder as well as pharmaceutical formulation. Conclusion: In this paper, a highly sensitive, accurate, and precise UPLC method with UV-Vis detection was developed and validated for quality control of MET and PAR in bulk as well as in pharmaceutical preparations.

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.

A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets

2021 ◽  
Author(s):  
Rochele Cassanta Rossi ◽  
Josué Guilherme Lisbôa Moura ◽  
Vanessa Mossmann ◽  
Patrícia Weimer ◽  
Pedro Eduardo Fröehlich
Keyword(s):  
Quality Control ◽  
Protease Inhibitor ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Forced Degradation ◽  
Control Analysis ◽  
Quality Control Laboratory ◽  
The Stability

Abstract Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.

scholarly journals Fast and selective HPLC-DAD method for determination of pholcodine and related substances

2011 ◽  
Vol 30 (2) ◽  
pp. 139 ◽  
Author(s):  
Ana Petkovska ◽  
Hristina Babunovska ◽  
Marina Stefova
Keyword(s):  
Quality Control ◽  
Degradation Products ◽  
Ammonium Hydroxide ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Real Sample Analysis ◽  
Related Substances ◽  
Structural Analogues ◽  
Reliable Methods

Quality control of pharmaceuticals requires development of fast, efficient and reliable methods for determination of active compounds as well as known and very often unknown impurities within defined concentration ranges. In this work, a simple and rapid HPLC-UV-DAD method for identification and quantification of pholcodine process related impurities and some degradation products was developed and validated. Pholcodine and its five structural analogues such as morphine, codeine, thebaine, oripavine, and papaverine were separated in less than 10 minutes using reversed phase LiChrospher C-8 column. For optimal chromatographic performance with reproducible retention times, gradient elution with 2% ammonium hydroxide in water and acetonitrile was used. The method was validated by establishing its selectivity, specifity, sensitivity, linearity, intra- and inter-day precision and robustness. All tested parameters confirmed that the method is suitable for determination of pholcodine and its five impurities in pharmaceutical drug samples. The results obtained from real sample analysis give support to the suitability of the proposed method for the purpose of quality control.

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