scholarly journals Development of a Unified Reversed-Phase HPLC Method for Efficient Determination of EP and USP Process-Related Impurities in Celecoxib Using Analytical Quality by Design Principles

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 809 ◽  
Author(s):  
Tim Tome ◽  
Zdenko Časar ◽  
Aleš Obreza
Keyword(s):  
Quality By Design ◽  
Reversed Phase ◽  
Hplc Method ◽  
Drug Substance ◽  
Main Peak ◽  
Analytical Quality ◽  
Mobile Phase Flow Rate ◽  
Column Temperature ◽  
Related Impurities

This article presents the development of a reversed-phase (RP) high-performance liquid chromatographic (HPLC) method for determination of process-related impurities in a celecoxib drug substance following Analytical Quality by Design (AQbD) principles. The method from European Pharmacopeia (EP) for celecoxib drug substance does not sufficiently separate celecoxib from its EP impurity B because the system suitability criterion is not achieved (resolution NLT 1.8). The same issue was observed with the proposed method from United States Pharmacopeia (USP) for celecoxib capsules, where EP impurity A elutes under the main peak. A new HPLC method was developed that eliminates the disadvantages of the two pharmacopeial methods and is capable of efficiently separating and determining all seven impurities listed in EP and the proposed USP monographs. The development of a new HPLC method started with method scouting, in which various C18 and phenyl stationary phases were tested. Improved selectivity was obtained only with a chiral stationary phase. An immobilized Chiralpak IA-3 column used in RP mode turned out to be the most appropriate for method optimization. The ratio of acetonitrile in the mobile phase, flow rate, and column temperature were recognized as critical method parameters (CMPs) and were further investigated using a central composite face response-surface design. A multiple linear regression (MLR) method was applied to fit the mathematical models on the experimental data to determine factor–response relationships. The models created show adequate fit and good prediction abilities. The Monte Carlo simulation method was used to establish the design space. The method developed was verified in terms of precision, sensitivity, accuracy, and linearity, and the results showed that the new method is suitable for determination of seven process-related impurities of celecoxib.

scholarly journals RP-HPLC Method Development and Validation for the Estimation of Lansoprazole in Presence of Related Substances by QbD Approach

2021 ◽  
pp. 138-150
Author(s):  
Sachin B. Gholve ◽  
Jaiprakash N. Sangshetti ◽  
Omprakash G. Bhusnure ◽  
Ram S. Sakhare ◽  
Pratap H. Bhosale ◽  
...  
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Method Development ◽  
Hplc Method ◽  
Drug Substance ◽  
Gastric Ulcers ◽  
Mobile Phase Flow Rate ◽  
Column Temperature ◽  
Rp Hplc

A rapid specific RP-HPLC method has been developed for the determination of Lansoprazole impurities in the drug substance. The control of pharmaceutical impurities is currently a critical issue in the pharmaceutical industry. The International Council for Harmonization (ICH) has formulated a workable guideline regarding the control of impurities. The objective of the recent study was to develop and validate a HPLC method for the quantitative determination of process-related impurities of Lansoprazole in pharmaceutical drug substance. Lansoprazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl] methyl]-sulfinyl]- 1H-benzimidazole is an proton pump inhibitor used in the management of gastric ulcers. Chromatographic identification of the impurities was carried out by response surface methodology, applying a three-level Box Behnken design with three center points. Three factors selected were a mobile phase, flow rate, column temperature. Evaluation of the main factor, their interaction, and the quadric effect on peak resolution were done on Waters Symmetry C8, 250 x 4.6mm, 5µm column is used for the development of the method. The mobile phase consists of buffer and acetonitrile. The flow rate of the mobile phase was 1.0 ml/min with gradient elution. The column temperature is ambient and the detection wavelength is 235 nm. The injection volume was 10 µL. The method was validated as per ICH guidelines for linearity in the range of 50-150 µg/ml and the LOD & LOQ values obtained were 0.437×10-4 and 0.1325×10-3 µg/ml respectively which specifies the method's sensitivity. The proposed method was successfully used to determine the Lansoprazole impurities in drug substances.

scholarly journals Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2691
Author(s):  
Tim Tome ◽  
Aleš Obreza ◽  
Zdenko Časar
Keyword(s):  
High Performance ◽  
Quality By Design ◽  
High Performance Liquid Chromatographic ◽  
Reversed Phase ◽  
Fractional Factorial ◽  
Linear Regression Method ◽  
Analytical Quality ◽  
Column Temperature ◽  
Related Impurities ◽  
Ropinirole Hydrochloride

This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.

scholarly journals ISOLATION, CHARACTERIZATION AND VALIDATION OF HPLC METHOD FOR QUANTIFICATION OF BIS-[10-(2-METHYL-4H-3-THIA-4,9-DIAZABENZO[F]AZULENE)]-1,4-PIPERAZINE IN AN ANTI-PSYCHOTIC DRUG SUBSTANCE, OLANZAPINE

2018 ◽  
Vol 10 (4) ◽  
pp. 22
Author(s):  
Suresh Babu Bodempudi ◽  
Ravi Chandra Babu Rupakula ◽  
Konda S. Reddy ◽  
Mahesh Reddy Ghanta
Keyword(s):  
Mobile Phase ◽  
Sodium Hydroxide Solution ◽  
Linear Regression Analysis ◽  
Sodium Dodecyl ◽  
Hplc Method ◽  
Drug Substance ◽  
Phase System ◽  
Column Temperature ◽  
Relative Standard

Objective: The main objective of present study was to Isolate, characterize and validate a reverse phase high performance liquid chromatographic method was validated for quantification of bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine in Olanzapine drug substance; it decreases the mental disorders in human body. The method is specific, rapid, precise and accurate for the separation and determination of bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine in Olanzapine drug substance form.Methods: The bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine of Olanzapine was resolved on a Zorbax RX-C 8, 250 mm X 4.6 mm, 5 micron column (L-1) using a mobile phase system containing 0.03 M sodium dodecyl sulphate in water pH 2.5 with 1 N sodium hydroxide solution and acetonitrile in the ratio of (Mobile phase A-52:48 v/v) and (Mobile phase B-buffer and Acetonitrile 30:70 v/v) by using the gradient program. The mobile phase was set at a flow rate of 1.5 ml/min and the volume injected was 20μl for every injection. The detection wavelength was set at 220 nm and the column temperature was set at 35 °C.Results: The proposed method was productively applied for the quantitative determination of bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo [f]azulene)]-1,4-piperazine in Olanzapine drug substance form. The linear regression analysis data for calibration plots showed a good linear relationship over a concentration range of 0.025to 0.903 µg/ml for bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine, 0.081-0.608 µg/ml for Olanzapine. The mean values of the correlation coefficient were 0.999 and 0.999 for bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine and Olanzapine. The method was validated as per the ICH guidelines. The detection limit (LOD) was about 0.007 µg/ml, 0.024 µg/ml and quantitation limit (LOQ) was about 0.024 µg/ml, 0.081 µg/ml for bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine and Olanzapine. The relative standard deviation was found to be 1.64 % and 2.18 % for bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine and Olanzapine.Conclusion: The validated HPLC method and the statistical analysis showed that the method is repeatable and selective for the estimation of the bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene)]-1,4-piperazine of the Olanzapine drug substance.

scholarly journals A Validated Stability-Indicating Liquid Chromatographic Method for the Determination of Lorcaserin and Related Impurities in DRUG Substance Supported by Quality by Design

2020 ◽  
Vol 58 (7) ◽  
pp. 661-671
Author(s):  
Dattatraya V Wani ◽  
Santosh N Mokale
Keyword(s):  
Quality By Design ◽  
Stress Condition ◽  
Ammonia Solution ◽  
Solution Ph ◽  
Column Temperature ◽  
Stability Indicating ◽  
Related Impurities ◽  
Stability Indicating Method ◽  
Liquid Chromatographic

Abstract Lorcaserin (LOR) is selective and potent antiobesity drug that targets the activation of the serotonin 5HT2C receptor. Here a novel, specific, sensitive stability indicating method was developed and validated for the quantitative determination of LOR and its process-related impurities using quality by design principles. By applying experimental design, the authors examine the multifactorial effect of parameters on the critical resolution pair and generated design space representing the robust design. LOR was subjected to stress condition and found stable at all condition, only found significant degradation at oxidative stress condition. The chromatographic separation of degradation product and its process-related impurities were achieved on a Phenomenox Luna phenyl-hexyl column (150 × 4.6 mm × 5 μm), with mobile phase consisting of 10 mM ammonium formate containing 0.1% ammonia solution; pH adjusted to 2.8 with trifluoroacetic acid as solvent A and methanol/acetonitrile (5/95) as solvent B delivered with gradient program at a flow rate of 1.0 mL/min, column temperature was maintained at 25°C and analytes were monitored at 220 nm. The injection volume was 5 μL. The developed RP-LC method was validated and found linear, accurate, specific, selective, precise and robust. The structure of impurities was confirmed by direct mass analysis.

Development and Validation of a Reversed-Phase HPLC Method for Determination of Alkaloids from Papaver somniferum L. (Papaveraceae)

2012 ◽  
Vol 95 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Jelena Acevska ◽  
Aneta Dimitrovska ◽  
Gjoshe Stefkov ◽  
Katerina Brezovska ◽  
Marija Karapandzova ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Ph Value ◽  
Reversed Phase ◽  
Hplc Method ◽  
Papaver Somniferum ◽  
Chromatographic Behavior ◽  
Organic Modifier ◽  
Column Temperature ◽  
Development And Validation

Abstract An HPLC method for the separation of six target alkaloids from Papaver somniferum L. (morphine, codeine, oripavine, thebaine, papaverine, and noscapine) was developed, optimized, and validated. The chromatographic behavior of these alkaloids was investigated using a reversed-phase chromatography at acidic and alkaline pH. The effects of ion-pairing agents, pH value of the mobile phase, concentration of the buffer components, mobile phase organic modifier, and column temperature were studied. Regardless of the large differences in their pKa values, all alkaloids were separated within a close retention window, and good peak shape was achieved for each of the six alkaloids. The proposed method has adequate selectivity, linearity, accuracy, precision, and reproducibility and is applicable for poppy straw.

scholarly journals Development and Validation of New RP-HPLC Method for Simultaneous Determination of Methyl and Propyl Parabens with Levetiracetam in Pure Form and Pharmaceutical Formulation

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Soad S. Abd El-Hay ◽  
Mostafa S. Mohram
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Pure Form ◽  
Mobile Phase Flow Rate ◽  
Column Temperature ◽  
Limit Of Quantitation

A simple and robust high-performance liquid chromatography (HPLC) method is described for the assay for levetiracetam (LTC), methyl paraben (MHB), and propyl paraben (PHB) either in their pure form or in commercial Levepsy® syrup. The method is selective and stability indicating and all chromatographic conditions were studied to obtain adequate separation of LTC, MHB, and PHB from their degradation products and from excipients. The HPLC separation was carried out on a RP C18 Hypersil BDS analytical column (150 mm × 4.6 mm ID) using gradient elution system. The mobile phase flow rate was 1.5 mLmin−1 and the column temperature was kept at 40°C. Complete separation of the studied components was obtained within a cycle time of 8 min. LTC, MHB, and PHB were eluted at 1.56, 5.86, and 7.85 min, respectively. Detection was carried out at 240 nm using a dual wavelength detector. The method has been validated for linearity, accuracy, precision, specificity, limit of detection, limit of quantitation, robustness, and ruggedness. The proposed method was successfully applied for the determination of LTC in the presence of parabens in Levepsy syrup.

Development and Validation of a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Identification, Assay and Estimation of Related Substances of Ivermectin in Bulk Drug Batches of Ivermectin Drug Substance

2021 ◽  
Author(s):  
Daoli Zhao ◽  
Rasangi M Wimalasinghe ◽  
Lin Wang ◽  
Abu M Rustum
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Degradation Products ◽  
Reversed Phase ◽  
Hplc Method ◽  
Drug Substance ◽  
Related Impurities ◽  
Rp Hplc ◽  
Bulk Drug

Abstract A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for the identification and assay of Ivermectin, including the identification and estimation of its process-related impurities and degradation products in bulk drug substance of Ivermectin. Analytes were separated on a HALO C18 column (100 mm × 4.6 mm I.D., 2.7 μm particle size) maintained at 40 °C (column temperature) with gradient elution. All analytes of interests were adequately separated within 25 min. All degradation products, process-related impurities and assay were monitored by ultraviolet detection at 254 nm. The new HPLC method described here successfully separated an isomer peak of the active pharmaceutical ingredient (API) from the major API peak. This newly separated isomer peak is around 1.2 to 1.5% (peak area) in typical API samples, and coelutes with the major API peak by all current HPLC methods. Quantitation limit of the HPLC method is 0.1% of target analytical concentration (~1.0 μg/mL). This method has been demonstrated to be accurate, robust, significantly higher degree of selectivity compared to the HPLC methods of Ivermectin drug substance reported in the literature and in the compendial HPLC methods prescribed in the current USA and European Pharmacopeia.

DEVELOPMENT AND VALIDATION OF THE PROCEDURE FOR QUANTITATIVE DETERMINATION OF IMPURITIES IN TABLETS “RANOLAZIN-NAN”

2021 ◽  
Vol 92 (2) ◽  
pp. 80-92
Author(s):  
V. B. Klimashevich ◽  
E. V. Kokusev ◽  
V. V. Gudovich ◽  
O. A. Kazyuchits ◽  
A. I. Zhebentyaev
Keyword(s):  
High Performance ◽  
Reversed Phase ◽  
Intermediate Precision ◽  
Column Temperature ◽  
Related Impurities ◽  
Stability Robustness ◽  
Quantitation Limit ◽  
The Stability ◽  
Development And Validation

The article presents the results of the research on the development of the procedure for determining related impurities by high-performance reversed-phase chromatography in the tablets “Ranolazin-NAN”. The conditions for samples preparation of ranolazine tablets, optimal conditions for the gradient mode of chromatography were selected using Zorbax Eclipse Plus C18 column: eluent A - 0,1% triethylamine buffer with pH 6,0 ± 0,1 (diluted with orthophosphoric acid) and acetonitrile in a ratio 70:30 v / v and eluent B - acetonitrile. The effect of pH medium (2,0, 6,0 and 9,0) on the efficiency of the column while studying the solutions of ranolazine and identified impurities was established. The suitability of the chromatographic system was proven and the specificity of the method for determining unidentified and identified impurities was proven. Linearity in the entire range of the procedure usage (from the quantitation limit to 125% (of the content of a single impurity)), correctness as well as precision at the level of reproductivity and intermediate precision, and the stability (robustness) of the method with small changes in the flow rate and column temperature were proven for the procedure of related impurities determination in Ranolazin-NAN tablets.

scholarly journals A Validated Reversed-Phase HPLC Method for the Determination of Vildagliptin from Tablet Dosage Form

2013 ◽  
Vol 2 (3) ◽  
pp. 90-98 ◽  
Author(s):  
Rahima Khatun ◽  
Md Mirazzunnabi
Keyword(s):  
Dosage Form ◽  
Theoretical Plate ◽  
Cost Effective ◽  
Reversed Phase ◽  
Hplc Method ◽  
Array Detector ◽  
Buffer Solution ◽  
Column Temperature ◽  
Tablet Dosage

A simple, rapid, precise and cost effective method has been developed and validated for determination of Vildagliptin in pharmaceutical tablet dosage form. The chromatographic separation was carried out with Shimpack VP-ODS, 150 × 4.6 mm, 5?m analytical column and mobile phase containing 0.02M phosphate buffer (pH 4.6) and acetonitrile at the ratio (80:20% v/v). pH of the buffer solution was adjusted with orthophosphoric acid. The instrumental settings include flow rate 0.7 ml/min, column temperature at 25ºC and detector wavelength of 210nm using a photodiode array detector. Theoretical plate for Vildagliptin was 6219 and tailing factor was 1.38. DOI: http://dx.doi.org/10.3329/ijpls.v2i3.15455 International Journal of Pharmaceutical and Life Sciences Vol.2(3) 2013: 90-98

Sign in / Sign up

Export Citation Format

Share Document