scholarly journals Development and Validation of a Stability Indicating LC Method for the Assay and Related Substances Determination of a Proteasome Inhibitor Bortezomib

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kasa Srinivasulu ◽  
Mopidevi Narasimha Naidu ◽  
Kadaboina Rajasekhar ◽  
Murki Veerender ◽  
Mulukutla Venkata Suryanarayana
Keyword(s):  
Formic Acid ◽  
Mobile Phase ◽  
Gradient Elution ◽  
Hplc Method ◽  
Forced Degradation ◽  
Balance Study ◽  
Stability Indicating ◽  
Related Substances ◽  
Mass Balance Study

A novel, simple, sensitive, stability indicating HPLC method was developed and validated for quantification of impurities (process related and degradants) and assay determination of bortezomib. Stability indicating power of the method was established by forced degradation experiments and mass balance study. The chromatographic separation was achieved with Waters SymmetryShield RP18 column using gradient elution using the mobile phase-A consists of a mixture of water-acetonitrile-formic acid (715 : 285 : 1, v/v/v) and the mobile phase-B consists a mixture of methanol-water-formic acid (800 : 200 : 1, v/v/v), respectively. The developed method is validated for parameters like precision, accuracy, linearity, LOD, LOQ, and ruggedness. Central composite experimental design (CCD) was applied to check the robustness of the method. The stability tests were also performed on drug substances as per ICH norms.

scholarly journals Stability Indicating RP-HPLC Method for Determination of Valsartan in Pure and Pharmaceutical Formulation

2010 ◽  
Vol 7 (1) ◽  
pp. 246-252 ◽  
Author(s):  
S. K. Patro ◽  
S. K. Kanungo ◽  
V. J. Patro ◽  
N. S. K. Choudhury
Keyword(s):  
Linear Response ◽  
Mobile Phase ◽  
Hplc Method ◽  
Forced Degradation ◽  
Control Analysis ◽  
Solution Stability ◽  
Stability Indicating ◽  
Quality Control Analysis ◽  
Rp Hplc

A simple, rapid and accurate and stability indicating RP-HPLC method was developed for the determination of valsartan in pure and tablet forms. The method showed a linear response for concentrations in the range of 50-175 µg/mL using 0.01 M NH4H2PO4(pH 3.5) buffer: methanol [50:50] as the mobile phase with detection at 210 nm and a flow rate of 1 mL/min and retention time 11.041 min. The method was statistically validated for accuracy, precision, linearity, ruggedness, robustness, forced degradation, solution stability and selectivity. Quantitative and recovery studies of the dosage form were also carried out and analyzed; the % RSD from recovery studies was found to be less than 1. Due to simplicity, rapidity and accuracy of the method, we believe that the method will be useful for routine quality control analysis.

scholarly journals VALIDATED GRADIENT STABILITY INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS QUANTIFICATION OF 11 RELATED SUBSTANCES IN THE COMBINED DOSAGE FORMS OF LAMIVUDINE AND TENOFOVIR DISOPEOXIL FUMARATE

2017 ◽  
Vol 9 (4) ◽  
pp. 61 ◽  
Author(s):  
C. Babu ◽  
N. Devanna ◽  
K. V.n. Suresh Reddy
Keyword(s):  
Mobile Phase ◽  
Ammonium Acetate ◽  
Dosage Forms ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Simultaneous Quantification ◽  
Related Substances ◽  
Drug Substances ◽  
Rp Hplc

Objective: Development of a stability-indicating reverse phase liquid chromatographic (RP-HPLC) method for the simultaneous quantification of 11 impurities in the combined dosage forms of lamivudine and tenofovir disoproxil fumarate drug substances.Methods: Efficient chromatographic separation of all analytes was achieved on a Waters X-terra RP18 column (150 x 4.6 mm, 3.5 mm) using mobile phase A (ammonium acetate buffer, pH adjusted to 5.0±0.05 with dilute orthophosphoric acid) and mobile phase B (mixture of methanol and ammonium acetate buffer in the ratio of 20:80) with the flow rate of 1.0 ml/min in gradient elution mode at 260 nm.Results: The method was validated in terms of the limit of detection, limit of quantification, linearity, accuracy, precision and robustness according to the international conference on harmonisation (ICH Q2R1). Regression analysis showed that the correlation coefficient (r2) is greater than 0.997 for individual active drug substances as well as their related substances. The method has proven very accurate (94.6 % to 108.2 % with % RSD not more than 4.9), highly precise (% RSD of the Intra-day and the inter-day study was not more than 8.9) and robust enough to deliver accurate results, when the chromatographic conditions were altered intentionally. Forced degradation studies were conducted in acidic, basic, thermal, photolytic, humid and peroxide stress conditions, where all the degradation peaks were monitored. Highest degradation of lamivudine was observed under oxidative stress condition and tenofovir was more susceptible to degradation under acidic and alkaline conditions.Conclusion: The present method is able to separate all the related compounds with each other and with the main drug substances with the resolution more than 2.0. The test solution was found to be stable in diluent up to 24 h. The mass balance of forced degradation of formulations, close to 99 %, made this method as a stability indicating method.

scholarly journals Development and validation of the stability-indicating LC-UV method for the determination of cefoselis sulphate

2012 ◽  
Vol 10 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Przemysław Zalewski ◽  
Judyta Cielecka-Piontek ◽  
Anna Jelińska
Keyword(s):  
Mobile Phase ◽  
Degradation Products ◽  
Kinetic Studies ◽  
Hplc Method ◽  
Assay Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
The Stability ◽  
Development And Validation

AbstractThe stability-indicating LC assay method was developed and validated for quantitative determination of cefoselis sulphate in the presence of degradation products formed during the forced degradation studies. An isocratic, RP-HPLC method was developed with C-18 (250 × 4.6 mm, 5 µm) column and 12 mM ammonium acetate-acetonitrile (95:5 V/V) as a mobile phase. The flow rate of the mobile phase was 1.0 mL min−1. Detection wavelength was 260 nm and temperature was 30°C. Cefoselis similarly to other cephalosporins was subjected to stress conditions of degradation in aqueous solutions including hydrolysis, oxidation, photolysis and thermal degradation. The developed method was validated with regard to linearity, accuracy, precision, selectivity and robustness. The method was applied successfully for identification and determination of cefoselis sulphate in pharmaceuticals and during kinetic studies.

scholarly journals Gradient HPLC-Diode Array Detector Stability-Indicating Determination of Lidocaine Hydrochloride and Cetylpyridinium Chloride in Two Combined Oral Gel Dosage Forms

2011 ◽  
Vol 94 (2) ◽  
pp. 503-512 ◽  
Author(s):  
Tarek S Belal ◽  
Rasha A Shaalan ◽  
Rim S Haggag
Keyword(s):  
Mobile Phase ◽  
Cetylpyridinium Chloride ◽  
Gradient Elution ◽  
Lidocaine Hydrochloride ◽  
Array Detector ◽  
Diode Array ◽  
Forced Degradation ◽  
Diode Array Detector ◽  
Stability Indicating

Abstract A simple, rapid, and selective HPLC-diode array detector method was developed for the simultaneous determination of lidocaine hydrochloride (LD) and cetylpyridinium chloride (CPC) in two combined pharmaceutical formulations. Effective chromatographic separation was achieved on a Zorbax SB-C8 (4.6 250 mm, 5 m particle size) column with gradient elution using a mobile phase composed of 0.05 M phosphoric acid and acetonitrile. The gradient elution started with 25 (v/v) acetonitrile, ramped up linearly to 85 in 5 min, and then was constant until the end of the run. The mobile phase was pumped at a flow rate of 1.2 mL/min. The multiple wavelength detector was set at 214 and 258 nm, and quantification of the analytes was based on measuring their peak areas. The retention times for LD and CPC were about 3.4 and 7.3 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, range, precision, accuracy, selectivity, robustness, LOD, and LOQ. Calibration curves were linear in the range of 5200 and 10400 g/mL for LD and CPC, respectively, with correlation coefficients >0.999. The proposed method was proven to be stability-indicating by the resolution of the two analytes from the related substance and potential impurity (2,6-dimethylaniline) as well as from forced-degradation products. The validated HPLC method was extended to the analysis of LD and CPC in two combined oral gel preparations for which the two analytes were successfully resolved from the pharmaceutical adjuvants and quantified with recoveries not less than 97.9.

scholarly journals New stability indicating RP-HPLC-PDA method for determination of mifepristone in bulk and tablet formulation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mohammad Mojeeb Gulzar Khan ◽  
Mohammad Faizan Saadique Deshmukh ◽  
Sandip Dinkar Firke ◽  
Abdul Talib Abdul Wahab ◽  
Mohan Ganpatrao Kalaskar ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Hplc Method ◽  
Tablet Formulation ◽  
Forced Degradation ◽  
Established Method ◽  
Potassium Dihydrogen ◽  
Stability Indicating ◽  
Quantitation Limit ◽  
Rp Hplc

Abstract Background Mifepristone is progestational and glucocorticoid hormone antagonist. The objective of this study is to develop simple and economical stability indicating RP-HPLC method for the determination of mifepristone in bulk and tablet formulation. Result The chromatographic separation was achieved on Qualisil BDS C8 column with mobile phase containing of mixture of Buffer (Potassium dihydrogen ortho phosphate, pH to 3.0 with ortho phosphoric acid) and Organic Solvent (Acetonitrile) 60:40 v/v pumped at flow rate 0.6 mL min−1. The detection of elute was performed using PDA detector at 305 nm. Mifepristone was eluted at 8.67 min. According to international conference on harmonization Q2(R1) guideline, method was validated and shows satisfactory results for accuracy, precision, linearity, ruggedness, robustness, detection limit, quantitation limit. The method indicated to be linear in the series of concentration 3–18 µg mL−1, and correlation coefficient was 0.9997. In acidic, basic, oxidative, thermal, photolytic forced degradation conditions, the peak of degradation product was clearly and well separated from drug peak without any interference in quantitative analysis. This represents stability indicating nature of established method. Conclusion The established RP-HPLC method is simple, accurate, specific, precise, robust, rugged, sensitive, and economical in nature which can be utilized for routine analysis of mifepristone in bulk and pharmaceutical formulation.

Chromatographic Separation of the Novel Hypoglycemic Drug Mitiglinide in its Bulk Powder and Pharmaceutical Formulation: Forced Degradation and Validated Stability-Indicating HPTLC/Densitometry and HPLC/UV Methods

2020 ◽  
Vol 103 (3) ◽  
pp. 736-742
Author(s):  
Maya S Eissa ◽  
Eman Darweish ◽  
Mohammed R Elghobashy ◽  
Mostafa A Shehata
Keyword(s):  
Stationary Phase ◽  
Flow Rate ◽  
Mobile Phase ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Relative Standard ◽  
Hypoglycemic Drug ◽  
Hptlc Method

Abstract Background Mitiglinide (MTG) is one of meglitinides group which are used for treatment of type two diabetes mellitus. Objective Mitiglinide (MTG) is a novel oral hypoglycemic drug. The present work adopts two stability-indicating chromatographic methods for determination of MTG after being exposed to forced degradation using 4 M methanolic HCl for 12 h. Methods The first method is HPTLC/densitometry using methanol:chloroform:acetic acid (5:2.5:0.3 by volume) as the eluting system and silica gel 60 GF254 as the stationary phase; the separated bands were then scanned at 220 nm. The second method is HPLC/UV in which acetonitrile:methanol:0.05 M potassium dihydrogen orthophosphate (pH 3.5) (40:25:35 by volume) was used as the mobile phase and a Zorbax SB-C8 (250 × 4.6 mm, 5 µm) column as a stationary phase, at a flow rate of 1 mL/min and UV detection at 220 nm. Results As a result of acid hydrolysis, two degradants were obtained. The first one was benzyl succinic acid to which this study was performed. The second one lacked configuration and was unreadable using UV spectrometry. Linearity was in the range of 8–48 µg/band MTG for HPTLC and 10–80 µg MTG for HPLC. LOD and LOQ values were 1.85 and 5.62 µg/band for the HPTLC method and 2.14 and 6.49 µg/mL for the HPLC method, respectively. The Recovery % was 100.03 ± 1.464 and 99.61 ± 1.44 using the HPTLC and HPLC methods, respectively. The relative standard deviations (RSD, %) for intra- and inter-day assays were 1.111 and 1.430 for the HPTLC method, respectively, and those for the HPLC method were 1.377 and 0.866, respectively. The RSD, %, for robustness testing was 1.162 (saturation time of mobile phase) and 1.592 (change in ratio of methanol content) for the HPTLC method and 1.377 (mobile phase composition), 1.713 (detector wavelength) and 1.770 (mobile phase flow rate) for the HPLC method. Conclusions The adopted methods were successfully applied for the determination of MTG in its pure form, in presence of its acid degradant and in its tablet dosage form. Highlights Statistical comparison between the results obtained from the developed methods and those obtained by the reported HPLC method showed no significance difference.

scholarly journals A Validated Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Tenofovir, Emtricitabine, and a Efavirenz and Statistical Approach to Determine the Effect of Variables

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Prashant S. Devrukhakar ◽  
Roshan Borkar ◽  
Nalini Shastri ◽  
K. V. Surendranath
Keyword(s):  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Accelerated Stability ◽  
Successful Separation ◽  
Combined Drugs

A simple, rapid, and stability-indicating RP-HPLC method for a combination of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) was developed and validated with the help of a suitable statistical software as an application tool for the quality by design. The drugs individually, and in combination, were subjected to forced degradation (thermal, photolytic, hydrolytic, and oxidative stress conditions) and accelerated stability studies (40 ± 1°C/75 ± 3% RH for three months). Successful separation of combined drugs from degradation products was achieved by gradient elution on a reverse-phase C18 column, using a mobile phase containing phosphate buffer (pH 3.5): acetonitrile at 1.5 mL min−1 flow rate, detection wavelength 256 nm, column oven temperature 25°C, and injection volume 10 μL. Linearity was established in the range of 20–300 μg mL−1, 24.5–367.5 μg mL−1 and 60–900 μg mL−1 for FTC, TDF, and EFV, respectively. The method was successfully applied for quantifying the drugs in marketed dosage forms and on stability samples.

Stability-Indicating RP-HPLC Method for the Estimation of Process-Related Impurities and Degradation Products in Fesoterodine Fumarate by Using a Mass Spectrometric Compatible Mobile Phase

2020 ◽  
Author(s):  
Nitin Kumar ◽  
D Sangeetha ◽  
L Kalyanraman
Keyword(s):  
Mobile Phase ◽  
Extended Release ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Forced Degradation ◽  
Preparative Hplc ◽  
Stability Indicating ◽  
Related Impurities ◽  
Relative Retention

Abstract The objective of the present work was to develop a sensitive, selective, accurate and precise stability-indicating HPLC method for quantification of degradation products and process-related impurities in fesoterodine fumarate extended-release tablets. The degradation profile was studied by conducting forced degradation studies and all the degradation products formed during degradation were separated. A chromatographic separation was achieved by using Waters Symmetry C18, 250 × 4.6 mm, 5 μm column, maintained at 30°C. Mobile phase A (0.05% trifluoroacetic acid in water) and mobile phase B (90% of 0.02% TFA in methanol and 10% of water) were used in gradient elution mode. A total of 75 μL of each solution was injected and peak responses were quantified at 220 nm. The method was found specific, precise, accurate, linear, rugged, robust and sensitive. During stability studies of fesoterodine fumarate extended-release tablets, one unknown impurity at relative retention time 1.37 was found increasing beyond the identification threshold. This impurity was isolated by using Preparative HPLC and structure was elucidated using mass and NMR spectroscopy. This method is a simple, inexpensive HPLC method that can be used as a routine quality control test for the estimation of impurities in fesoterodine fumarate extended-release tablets.

scholarly journals DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF POTENTIAL DEGRADATION PRODUCTS OF DIFLUPREDNATE IN OPHTHALMIC EMULSION

2018 ◽  
Vol 10 (9) ◽  
pp. 79 ◽  
Author(s):  
Murlidhar V. Zope ◽  
Rahul M. Patel ◽  
Ashwinikumari Patel ◽  
Samir G. Patel
Keyword(s):  
Quantitative Determination ◽  
Degradation Product ◽  
Mobile Phase ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Rp Hplc

Objective: The objective of the current study was to develop and validate a simple, robust, precise and accurate RP-HPLC (reverse phase-high performance liquid chromatography) method for the quantitative determination of potential degradation products of Difluprednate (DIFL) in the ophthalmic emulsion.Methods: Chromatographic separation was achieved on the YMC pack ODS-AQ (150× 4.6) mm, 3μm column with a mobile phase containing a gradient mixture of mobile phase A (0.02M Ammonium formate buffer pH 4.5 adjusted with formic acid) and Acetonitrile as mobile phase B, at flow rate of 1.5 ml/min and with UV detection at 240 nm.Results: The peak retention time of DIFL was found at about 17.2 min, the RRT of degradation product-1 (DP-1), degradation product-2 (DP-2), and degradation product-3 (DP-3), were found to be about 0.49, 0.65 and 0.79 respectively (calculated with respect to Difluprednate). Stress testing was performed in accordance with an ICH (international council for harmonisation) guideline Q1A (R2) [1]. The method was validated as per ICH guideline Q2 (R1)[2]. The calibration curve was found to be linear in the concentration range of 0.1 to 0.75 µg/ml for Difluprednate, DP-1, DP-2 and DP-3. The LOD (Limit of detection) was found to be 0.1µg/ml and LOQ (Limit of quantification) of 0.15µg/ml for Difluprednate, DP-1, DP-2 and DP-3 respectively. The recovery from LOQ to 150% was within 90-110%. The forced degradation data confirms the stability indicating the nature of the method.Conclusion: A simple, robust, precise and accurate RP-HPLC method for the quantitative determination of potential degradation products of Difluprednate in the ophthalmic emulsion was developed and validated. 

Development and Validation of HPLC Determination of related Substances in A Novel Anticonvulsant agent Epimidin

2021 ◽  
pp. 3223-3231
Author(s):  
Hanna I. Severina ◽  
Svitlana M. Gubar ◽  
Ivan V. Bezruk ◽  
Anna S. Materiienko ◽  
Liudas Ivanauskas ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Phosphate Buffer Solution ◽  
Anticonvulsant Drug ◽  
Strong Acid ◽  
Gradient Elution ◽  
Stress Conditions ◽  
Drug Candidate ◽  
Buffer Solution ◽  
Related Substances

1-(4-methoxyphenyl)-5-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxo-ethyl]pyrazolo[3,4-d]pyrimidin-4-one has been reported as a promising new anticonvulsant drug candidate with a code name “Epimidin”. A new HPLC method for the related substances determination of potential active pharmaceutical ingredient has been developed and validated. The method uses ACE C18 column (250x4.6mm, 5µm) and gradient elution. Mobile phase consisted of a mixture of methanol R (mobile phase A) and phosphate buffer solution with triethanolamine, adjusted to pH 7.0 (mobile phase B). During the analysis, the ratio of mobile phases was changing according to a gradient mode at a flow rate of 1ml/min. The DAD detection was set at 240nm. The method was validated according to the ICH guidelines and requirements of State Pharmacopoeia of Ukraine. Drug substance was thoroughly explored for stability assessments under various stress conditions such as high temperature, as well as the influence of strong acid and base and oxidizing agents. The obtained solutions were analyzed by HPLC and LC/MS. It has been shown that the substance Epimidin was not resistant to the action of peroxide, alkali and acid decomposition – the mentioned stress conditions lead to the formation of unidentified impurities.

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