scholarly journals Development of HPLC Method for Stress Testing of Combination of Two Drugs Using Design of Experiment Concept

2019 ◽  
Vol 11 (06) ◽  
Author(s):  
Mohini Bajaj ◽  
Sanju Nanda
Keyword(s):  
Design Of Experiment ◽  
Stress Testing ◽  
Degradation Products ◽  
Hold Time ◽  
Hplc Method ◽  
Array Detector ◽  
Organic Modifier ◽  
Primary Stage ◽  
Diethylcarbamazine Citrate ◽  
Secondary Stage

This study was conducted to develop, an High Performance Liquid Chromatography using photodiode array detector (HPLC-PDA) method to analyse the samples generated by the stress testing of antifilarial combination (albendazole and diethylcarbamazine citrate) in the solution state. The concept of Quality by Design (Design of Experiment, DoE) approach was used for the development. For the separation of the drugs and its degradation products (DPs), DoE was applied in two stages, i.e., primary parameter stage where factors having major effect were selected. This stage gives us CQA (Critical Quality Attribute) which along with minor factors affecting were varied to get the secondary design. For each of the stage a different design was selected; for primary stage IV optimal design (Response Surface Method) was selected whereas for secondary stage, Taguchi orthogonal array design was selected. The major primary parameters affecting the HPLC method as screened by preliminary studies were the buffer pH, organic modifier (methanol or acetonitrile), initial hold time (start of gradient) and gradient time. The primary stage was completed successfully. The results were compiled in form of resolution of peak from next peak and analysed by DoE. The process fixed the values for buffer pH (4.38), organic modifier (acetonitrile) and gradient time (30 min). The CQA from primary run was initial hold time. This parameter along with other parameters: initial and final concentration of organic modifier, buffer type (phosphate or acetate), buffer strength (mM) and oven temperature were further varied and samples withdrawn were analysed. The data of secondary design was compiled in the form of resolution (R), analysed by Design Expert and final value for secondary parameter for HPLC method were fixed. The resolution of the peaks for some secondary runs was sufficient reflecting some type of interaction between the drugs and/or degradation products.

Development and validation of a fast and simple HPLC method for the simultaneous determination of aniline and its degradation products in wastewater

2016 ◽  
Vol 8 (30) ◽  
pp. 5949-5956 ◽  
Author(s):  
Soumia Boulahlib ◽  
Ali Boudina ◽  
Kahina Si-Ahmed ◽  
Yassine Bessekhouad ◽  
Mohamed Trari
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Reversed Phase ◽  
Hplc Method ◽  
Array Detector ◽  
Simple Method ◽  
Photodiode Array Detector ◽  
Photodiode Array ◽  
Development And Validation

In this study, a rapid and simple method based on reversed-phase high performance liquid chromatography (RP-HPLC) using a photodiode array detector (PDA) for the simultaneous analysis of five pollutants including aniline and its degradation products, para-aminophenol, meta-aminophenol, ortho-aminophenol and phenol, was developed.

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 DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR DETERMINATION OF β-ACETYLDIGOXIN

2016 ◽  
Vol 9 (1) ◽  
pp. 54
Author(s):  
Megha Sharma ◽  
Neeraj Mahindroo
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Hplc Method ◽  
Stability Study ◽  
Array Detector ◽  
Forced Degradation ◽  
Simple Method ◽  
Stability Indicating ◽  
Rp Hplc

Objective: The objective of the present study was to develop and validate a novel stability indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for determination of β-acetyldigoxin, an active pharmaceutical ingredient (API).Methods: The chromatographic separation was carried out on Agilent Technologies 1200 series HPLC system equipped with photo diode array detector and C-18 (4.6x250 mm, 5 µ) column. The mobile phase consisted of water: acetonitrile (65:35 v/v), delivered at a flow rate of 1.5 ml/min and eluents were monitored at 225 nm.Results: The retention time of β-acetyldigoxin was 9.2 min. The method was found to be linear (R2= 0.9995) in the range of 31.25-500 µg/ml. The accuracy studies showed the mean percent recovery of 101.02%. LOD and LOQ were observed to be 0.289 µg/ml and 0.965 µg/ml, respectively. The method was found to be robust and system suitability testing was also performed. Forced degradation analysis was carried out under acidic, alkaline, oxidative and photolytic stress conditions. Significant degradation was observed under tested conditions, except for oxidative condition. The method was able to separate all the degradation products within runtime of 20 min and was able to determine β-acetyldigoxin unequivocally in presence of degradation products.Conclusion: The novel, economic, rapid and simple method for analysis of β-acetyldigoxin is reported. The developed method is suitable for routine quality control and its determination as API, and in pharmaceutical formulations and stability study samples.

Development and Validation of a Stability-Indicating HPLC Method for Imidapril and Its Degradation Products Using a Design of Experiment (DoE) Approach

2017 ◽  
Vol 100 (6) ◽  
pp. 1727-1738 ◽  
Author(s):  
Abiramasundari Arumugam ◽  
Amita Joshi ◽  
Kamala K Vasu
Keyword(s):  
Flow Rate ◽  
Design Of Experiment ◽  
Degradation Products ◽  
Desirability Function ◽  
Hplc Method ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Two Factors ◽  
Derringer’S Desirability Function ◽  
Imidapril Hydrochloride

Abstract The present work focused on the application of design of experiment (DoE) principles to the development and optimization of a stability-indicating method (SIM) for the drug imidapril hydrochloride and its degradation products (DPs). The resolution of peaks for the DPs and their drug in a SIM can be influenced by many factors. The factors studied here were pH, gradient time, organic modifier, flow rate, molar concentration of the buffer, and wavelength, with the aid of a Plackett–Burman design. Results from the Plackett–Burman study conspicuously showed influence of two factors, pH and gradient time, on the analyzed response, particularly, the resolution of the closely eluting DPs (DP-5 and DP-6) and the retention time of the last peak. Optimization of the multiresponse processes was achieved through Derringer’s desirability function with the assistance of a full factorial design. Separation was achieved using a C18 Phenomenex Luna column (250 × 4.6 mm id, 5 µm particle size) at a flow rate of 0.8 mL/min at 210 nm. The optimized mobile phase composition was ammonium–acetate buffer (pH 5) in pump A and acetonitrile–methanol (in equal ratio) in pump B with a run time of 40 min using a gradient method.

scholarly journals RP-HPLC Estimation of Bumetanide and its Impurities in Oral Solid Dosage Form

2019 ◽  
Vol 31 (10) ◽  
pp. 2215-2221
Author(s):  
P. Suresh Kumar ◽  
G.V. Krishna Mohan ◽  
A. Naga Babu
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Drug Product ◽  
Pharmaceutical Formulations ◽  
Hplc Method ◽  
Fixed Dose ◽  
Array Detector ◽  
Rp Hplc ◽  
Photodiode Array Detector ◽  
Limit Of Quantitation

A novel and simultaneous stability indicating RP-HPLC method has been developed for quantitative analysis of bumetanide in fixed dose pharmaceutical formulations. Bumetanide and its degradation products are well separated by the Discovery C18, 250 × 4.6 mm, 5 μm column as a stationary phase and (50:50 v/v) of 0.1 % o-phthalaldehyde and acetonitrile as a mobile phase. All the compounds are monitored using photodiode array detector at 254 nm with an isocratic method and the flow rate of 1.0 mL/min was maintained. Validation of method was performed as per International Council for Harmonization (ICH) guidelines and the parameters namely; precision, accuracy, specificity, stability, robustness, linearity, limit of quantitation (LOQ) and limit of detection (LOD) were evaluated. The linearity of the proposed method was found to be 0.315-1.875 μg/mL for bumetanide and its impurities. The developed method is more economical and suitable for laboratory use because of solvent consumption is very less. Hence, the developed method can be used for the determination of bumetanide and its impurities in drug product stability studies and pharmaceutical formulations.

scholarly journals Quantification of Pimavanserin in Bulk and Tablet Dosage Form Using A Stability Indicating High Performance Liquid Chromatographic Method

2018 ◽  
Vol 24 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Geetha Bhavani Koduri ◽  
Hari Babu Bollikolla ◽  
Ramachandran Dittakavi ◽  
Srinivasu Navuluri
Keyword(s):  
High Performance ◽  
Dosage Form ◽  
Degradation Products ◽  
Antipsychotic Agent ◽  
Hplc Method ◽  
Array Detector ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Stability Indicating ◽  
Tablet Dosage

Background: Pimavanserin, an antipsychotic agent, is used to treat patients suffering with Parkinson's disease. Till now no stability indicating reverse phase HPLC method was reported for the quantification of pimavanserin in bulk and tablet dosage form. Hence in the present study, a new sensitive, precise and accurate stability indicating reverse phase HPLC method with photodiode array detector has been developed for the quantification of pimavanserin in bulk and tablet dosage form. Methods: Separation and analysis of pimavanserin was achieved on Kromasil C18 (5 µm, 250 mm × 4.6 mm) column using 0.1M NaH2PO4, methanol and acetonitrile in ratio of 55:30:15 (v/v/v) as mobile phase at 25°C. The flow rate was 1.0 ml/min. The effluents were monitored with detector set at 239 nm. The method validation was done with regard to the guidelines by the International Conference on Harmonization. Pimavanserin was subjected to acid, alkali and neutral hydrolysis, hydrogen peroxide oxidation, thermal degradation, and photo (sunlight) degradation. Results: Linear relationship was obtained between the concentration of drug and peak area response in the range of 4.25-34.0 µg/ml. The limits of detection and quantitation were found to be 0.027 µg/ml and 0.089 µg/ml, respectively. All the validation characteristics were within the acceptance criteria. The peaks of degradation products were well resolved from the pimavanserin peak. Conclusion: The developed and validated method is able to quantify the pimavanserin in the presence of degradation products.

Development and Validation of a Stability Indicating RP-HPLC Method for Hydrocortisone Acetate Active Ingredient, Propyl Parahydroxybenzoate and Methyl Parahydroxybenzoate Preservatives, Butylhydroxyanisole Antioxidant, and Their Degradation Products in a Rectal Gel Formulation

2015 ◽  
Vol 98 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Magda Ascaso ◽  
Pilar Pérez-Lozano ◽  
Mireia García ◽  
Encarna García-Montoya ◽  
Montse Miñarro ◽  
...  
Keyword(s):  
Active Ingredient ◽  
Active Substance ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Hydrocortisone Acetate ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
The Stability

Abstract A stability indicating method was established through a stress study, wherein different methods of degradation (oxidation, hydrolysis, photolysis, and temperature) were studied simultaneously to determine the active ingredient hydrocortisone acetate, preservatives propyl parahydroxybenzoate, and methyl parahydroxybenzoate, antioxidant butylhydroxyanisole (BHA), and their degradation products in a semisolid dosage gel form. The proposed method was suitably validated using a Zorbax SB-Phenyl column and gradient elution. The mobile phase consisted of a mixture of methanol, acetonitrile, and water in different proportions according to a planned program at a flow rate of 1.5 mL/min. The diode array detector was set at 240 nm for the active substance and two preservatives,and 290 nm for BHA. The validation study was conducted according to International Conference on Harmonization guidelines for specificity, linearity, repeatability, precision, and accuracy. The method was usedfor QC of hydrocortisone acetate gel and for the stability studies with the aim of quantifying the active substance, preservatives, antioxidant, and degradation products. It has proved to be suitable as a fast and reliable method for QC.

scholarly journals Stability Indicating Simultaneous Validation of Telmisartan and Cilnidipine with Forced Degradation Behavior Study by RP-HPLC in Tablet Dosage Form

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Reema H. Rupareliya ◽  
Hitendra S. Joshi
Keyword(s):  
Correlation Coefficient ◽  
Degradation Products ◽  
Hplc Method ◽  
Array Detector ◽  
Forced Degradation ◽  
Solution Stability ◽  
Stability Indicating ◽  
Stress Studies ◽  
Rp Hplc ◽  
Behavior Study

A simple, precise, and accurate RP-HPLC method has been developed and validated for the simultaneous assay of Telmisartan and Cilnidipine in tablets. Isocratic RP-HPLC method was developed on Waters C18 250×4.6 mm, 5 μm column using mobile phase as acetonitrile (ACN): buffer pH 3.0 with orthophosphoric acid (68 : 32) at a flow rate of 1.0 mL/min and the detection was carried out at 245 nm using photodiode array detector. Forced degradation study was carried out by oxidation, hydrolysis, photolysis, and heating the drug. The method was validated for specificity, linearity, precision, accuracy, robustness, and solution stability. The method was found to be linear in the concentration range of 40–160 μg/mL with correlation coefficient of 0.9990 for Telmisartan and 10–40 μg/mL with correlation coefficient of 0.9989 for Cilnidipine. Degradation products produced as a result of stress studies did not interfere with the detection of agomelatine; therefore, the assay can be considered to be stability indicating.

scholarly journals Application of Response Surface Methodology in Development and Optimization of Stability Indicating RP-HPLC Method for Determination of Tolvaptan in Bulk and Formulation

2021 ◽  
pp. 137-148
Author(s):  
A. S. Sutar ◽  
C. S. Magdum
Keyword(s):  
Response Surface Methodology ◽  
Response Surface ◽  
Design Of Experiment ◽  
Mobile Phase ◽  
Method Development ◽  
Degradation Products ◽  
Hplc Method ◽  
Stability Indicating ◽  
Rp Hplc

Design of Experiment assisted stability indicating RP-HPLC was developed and optimized using response surface methodology for determination of Tolvaptan.  Mobile phase was developed and optimized using Design of Experiment with response surface methodology. Acetonitrile and phosphate buffer with pH 5.5 (70:30% V/V) was optimized as mobile phase. The flow rate was maintained at 1ml/min. Stress studies were performed as per guidelines. Method was validated in accordance with regulatory requirements and results were within specified limits of regulatory guidelines. Tolvaptan was eluted at 3.24 min. It shows linearity from 2.5-15 µg/ml. Coefficient of correlation was 0.999, LOD and LOQ values were 1.0871 (µg/ml) and 3.2942 (µg/ml). Precision was determined with % RSD of 0.8669 and 0.9709%, mean percentage Recovery value was found to be 99.88 ±1.2. All stress degradation products are very well resolved from drug peak which indicate suitability indicating nature of the developed method. Design of Experiment technique can help in fast and economical optimization of mobile phase which inturn will save time for method development. The developed method is simple, accurate, sensitive which can be utilised as stability indicating method for identification of degradation products in routine analysis of the drug.

scholarly journals A Validated New Gradient Stability-Indicating LC Method for the Analysis of Doripenem in Bulk and Injection Formulation

2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Singaram Kathirvel ◽  
Garikapati Devalarao
Keyword(s):  
Mobile Phase ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Active Pharmaceutical Ingredient ◽  
Hplc Method ◽  
Array Detector ◽  
Limit Of Quantification ◽  
Mobile Phase Flow Rate ◽  
Phase Gradient ◽  
Stability Indicating

A sensitive, precise, specific, linear, and stability-indicating gradient HPLC method was developed for the estimation of doripenem in active pharmaceutical ingredient (API) and in injectable preparations. Chromatographic separation was achieved on C18 stationary phase with a mobile phase gradient consisting of acetonitrile, methanol, and pH 5.2 phosphate buffer. The mobile phase flow rate was 0.8 mL/min, and the eluted compounds were monitored at 210 nm. The method is linear over the range of 0.335 to 76.129 µg/mL. The correlation coefficient was found to be 0.999. The numbers of theoretical plates and tailing factor for doripenem were 53021 and 0.9, respectively. Doripenem was subjected to the International Conference on Harmonization (ICH) prescribed hydrolytic (acid, base, and neutral), oxidative, photolytic, and thermal stress conditions. Among all the above-mentioned conditions, the drug was found to be stable under photolytic degradation. Peak homogeneity data for doripenem in the chromatograms from the stressed samples obtained by use of the photodiode array detector demonstrated the specificity of the method for analysis of doripenem in presence of the degradation products. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, and robustness.

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