Developing a Validated HPLC Method for Quantification of Ceftazidime Employing Analytical Quality by Design and Monte Carlo Simulations

2021 ◽  
Author(s):  
Ranjot Kaur ◽  
Sumant Saini ◽  
Asha Patel ◽  
Teenu Sharma ◽  
Ripandeep Kaur ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Flow Rate ◽  
Analytical Method ◽  
Mobile Phase ◽  
Quality By Design ◽  
Hplc Method ◽  
Superior Performance ◽  
Analytical Quality ◽  
Method Performance

Abstract Background Ceftazidime, a third-generation cephalosporin, is widely used in the treatment of lung infections, often given as “off-label” nebulization. There is need for developing a sensitive and robust analytical method to compute aerodynamic properties of ceftazidime following nebulization. Objective The current study entails development of a simple, accurate and sensitive high-performance liquid chromatography method (HPLC) for ceftazidime estimation, employing the principles of analytical quality-by-design (AQbD) and Monte Carlo simulations. Methods Selection of critical material attributes (CMAs) affecting method performance was accomplished by factor screening exercise. Subsequently, the influential CMAs, i.e., mobile phase ratio and flow rate, were systemically optimized using a face-centred cubic design for the chosen critical analytical attributes (CAAs). The factor relationship(s) between CMAs and CAAs was explored employing 3 D-response surface and 2 D-contour plots, followed by numerical as well as graphical optimization, for establishing the optimal chromatographic conditions. The obtained method operable design region was validated by Monte Carlo simulations for defect rate analysis. Results The optimized HPLC conditions for estimating ceftazidime were acetonitrile to acetic acid solution (75:25) as mobile phase at a flow rate of 0.7 mL/min, leading to Rt of 4.5 min and peak tailing ≤ 2. Validation studies, as per ICH Q2(R1) guidance’s, demonstrated high sensitivity, accuracy and efficiency of the developed analytical method with LOD of 0.075 and LOQ of 0.227 µg/mL. Application of this chromatographic method was extrapolated for determining aerodynamic performance by nebulizing ceftazidime at flow rate of 15 L/min using next-generation impactor. The study indicated superior performance, sensitivity and specificity of the developed analytical system for quantifying ceftazidime. Conclusions Application of AQbD approach, coupled with Monte Carlo simulations, aided in developing a robust HPLC method for estimation of ceftazidime per se and on various stages of impactor.

STABILITY INDICATING LIQUID CHROMATOGRAPHIC ASSESSMENT OF DOLUTEGRAVIR BY AQBD APPROACH – CENTRAL COMPOSITE DESIGN

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (10) ◽  
pp. 44-51
Author(s):  
G. Sunitha ◽  
◽  
P. D Anumolu ◽  
C.V.S Subrahmanyam ◽  
G Mounika ◽  
...  
Keyword(s):  
Flow Rate ◽  
Analytical Method ◽  
Mobile Phase ◽  
Dosage Form ◽  
Method Development ◽  
Degradation Products ◽  
Hplc Method ◽  
Limit Values ◽  
Mass Spectral ◽  
Theoretical Plates

Based on the current regulatory requirements for analytical method development, a RP-HPLC method for quality control of dolutegravir in dosage form has been optimized using analytical quality by design (AQbD) approach. Experimental observations were analysed by full factorial experimental design in Sigmatech software with two variables (flow rate and % organic mobile phase) whilst the number of theoretical plates was considered as response. The analytical method conditions were optimized as mobile phase (40:60 % V/V) consisting of acetonitrile and ammonium formate buffer, pH 3.0 pumped at a flow rate of 0.6 mL/min in an isocratic mode on SPOLAR C18 Column (250 x 4.6mm, 5μm) with run time of 15 min. The plot between peak area vs. concentration was rectilinear in the range of 5-30 μg/mL with detection and quantification limit values at 0.01 and 0.3μg/mL, respectively at retention time of 13 min. The predicted data from contour diagram for theoretical plates was verified virtually and it was contented with concrete experimental data. The method was validated as per ICH guidelines. The proposed method was pertinent for assay of marketed dosage form (Tivicay) and further extended to quantify the drug in prevalence of degradation products. Degradation pathways of dolutegravir were postulated and characterized by IR and mass spectral data.

Degradation Profiling of Lisinopril and Hydrochlorothiazide by RP- HPLC method with QbD Approach

2021 ◽  
pp. 270-274
Author(s):  
Kalleshvar P. Jatte ◽  
R. D. Chakole ◽  
M. S. Charde
Keyword(s):  
Particle Size ◽  
Quality Control ◽  
Flow Rate ◽  
Mobile Phase ◽  
Dosage Form ◽  
Quality By Design ◽  
Hplc Method ◽  
Rp Hplc ◽  
Tablet Dosage ◽  
Gradient Mode

RP-HPLC method was developed for the estimation of Lisinopril and Hydrochlorothiazide in tablet dosage form with the help of Quality by Design (QbD) approaches. In this method concentration of each drug was obtained by using the absorptivity values calculated for drug wavelength 226.0 nm and solving the equation. The RP-HPLC method was performed C18-(100mm x 4.6 mm,)2.5 μm particle size in gradient mode, and the sample was analysed using methanol 45.0 ml and 55.0 ml (pH 3.3 0.05% OPA with TEA) as a mobile phase at a flow rate of 0.8 ml/min and detection at nm. By the retention time for Lisinopril and Hydrochlorothiazide found 3.39 and 4.59 min respectively. Validation related the method is specific, rapid, accurate, precise, reliable, and reproducible. Calibration plots by both HPLC were linear over the 5-25 and 12.5-62.5 μg/ml for Lisinopril and Hydrochlorothiazide respectively, and recoveries from tablet dosage form were between 99.02 and 100.00 %. The method can be used for routine of the quality control in pharmaceuticals. The degradation profiling of Lisinopril and Hydrochlorothiazide were also carried out.

scholarly journals ANALYTICAL QUALITY-BY-DESIGN (AQBD) APPROACH FOR THE DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE ESTIMATION OF LAMOTRIGINE IN BULK AND TABLET FORMULATION

2021 ◽  
Vol 10 (5) ◽  
pp. 3591-3596
Author(s):  
Manisha P. Puranik
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
High Performance ◽  
Quality By Design ◽  
Active Pharmaceutical Ingredient ◽  
Reversed Phase ◽  
Hplc Method ◽  
Analytical Technique ◽  
Rp Hplc ◽  
Ich Guideline

The current analytical exploration illustrated developing a reversed-phase high-performance liquid chromatography (RP-HPLC) technique and consequent substantiation for analyzing lamotrigine (LAM) active pharmaceutical ingredient (API) using a Quality-by-design (QbD) approach (Central Composite Design), in bulk product as well as in the tablet formulations. In this experiment, based on systematic scouting, four key components (viz., mobile phase, column, flow-rate, and wavelength) were studied by the RP-HPLC method. 13 experimental runs were done with acetonitrile (ACN) (40-60% v/v) having flow-rate in the range 0.8 mL/min to 1.2 mL/min. The proposed analytical method was thoroughly corroborated in terms of ruggedness linearity, robustness, accuracy, and precision in accordance with ICH guideline Q2A and ICH guideline Q2B. Under the optimum chromatographic environment; Intersil C8 column of 250 mm length, 4.6 mm (i.d.); 20 μL injection volume; and mobile phase ACN: Methanol (60:40 v/v), a retention time of 2.542 min was noticed at 220 nm detection wavelength. The method was found to be extremely reproducible, accurate, linear, precise, robust, and economically adequate to execute the estimation. The intended analytical technique was thoroughly assessed through statistical tools and could be an imperative concern for the habitual scrutiny of LAM in bulk products and its formulation.

scholarly journals Quality by Design Approach for an Orally Disintegrating Tablet Analytical Method Validation

2018 ◽  
Vol 10 (01) ◽  
Author(s):  
G. Demire ◽  
D. Saray ◽  
B. Yaman, A. Turkyilmaz Yaman ◽  
A. Turkyilmaz
Keyword(s):  
Analytical Method ◽  
Method Development ◽  
Quality By Design ◽  
Hplc Method ◽  
Method Performance ◽  
Analytical Method Validation ◽  
Orally Disintegrating Tablet ◽  
Method Development And Validation ◽  
Quality By Design Approach ◽  
Development And Validation

Quality by Design (QbD) is well established in the pharmaceutical industry for pharmaceutical development and manufacturing processes. The knowledge obtained during development may support the establishment of a design space and determines suitable process controls. This same QbD principle has been applied to the development of analytical methods and is termed “Analytical Quality by Design” (AQbD). Analogous to process QbD, the outcome of AQbD is well understood, fit for purpose, and robust method that consistently delivers the intended performance throughout its life cycle. The present work is aimed to develop an AQbD approach to analytical method development and validation based of Tadalafil and its impurities by the NP-HPLC method. The other objective of this work is to establish an in-depth understanding of the method and build in the quality during the method development to ensure optimum method performance over the lifetime of the product.

scholarly journals Analytical Quality by Design as an Important Tool to Determine the Best Analytical Conditions for Isoniazid and Its Respective Succinylated Prodrug

2020 ◽  
Author(s):  
Denise Rampini ◽  
Renan Vinícius de Araújo ◽  
Rodrigo Esteves Foitinho ◽  
Felipe Rebello Lourenço ◽  
Jeanine Giarolla
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Health Concern ◽  
Major Influence ◽  
Analytical Quality ◽  
Pareto Chart ◽  
Test Conditions ◽  
Analytical Test ◽  
The Impact

Abstract Background Tuberculosis is a worldwide health concern and isoniazid is the most used and considered one of the most effective drugs for its treatment. The “quality” concept must be incorporated into the final pharmaceutical product, according to the quality by design (QbD) definition. Therefore, the determination of analytical test conditions is extremely important and the design of experiments (DoE) becomes a very useful tool. Objective This paper used the concept of QbD to assist the development of analytical conditions for isoniazid and its respective prodrug, applying HPLC. Method HPLC analytical methodologies were developed for isoniazid and its succinylated derivative. The experimental design was carried out using three analytical parameters at three levels. Four chromatographic responses were studied. The impact of analytical parameters on chromatographic responses was assessed using a Pareto chart. Regression models were obtained using multiple regression analysis. DoE analysis was conducted using the Minitab® program and the experiments were performed sequentially, with varying factors. Results We identify three main risk parameters: mobile phase (high), flow rate (moderate), and pH of buffer (moderate). The ratio of mobile phase buffer (X2) and mobile phase pH (X3) had a major influence on the peak resolutions (Y3). The capacity factors for iso-suc (Y1) and isoniazid (Y2) peaks should be within 3–9 and 4–10, respectively. The peak resolutions between iso-suc and isoniazid (Y3) should be above two. Conclusions We designed 27 experiments, obtaining 1.0 mL/min flow rate, 95% buffer in the mobile phase, and pH 7.0 as the optimal analytical conditions. Highlights Analytical Quality by Design was used as an important tool to determine the best analytical test conditions for isoniazid and its respective prodrug - succinylated isoniazid

ANALYTICAL QUALITY BY DESIGN APPROACH IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF DUVELISIB

2021 ◽  
pp. 99-108
Author(s):  
SRUJANI CH ◽  
ANNAPURNA P ◽  
NATARAJ KS ◽  
KRISHNA MANJARI PAWAR A
Keyword(s):  
Flow Rate ◽  
Retention Time ◽  
Quality By Design ◽  
Hplc Method ◽  
Design Approach ◽  
Analytical Quality ◽  
Column Temperature ◽  
Rp Hplc ◽  
Validation Parameters ◽  
Quality By Design Approach

Objective: A simple, accurate, and robust RP-HPLC method was developed and validated for the estimation of Duvelisib using analytical quality by design approach. Methods: The critical method parameters (CMP) were systematically optimized using box-Behnken design (BBD). The CMP’s selected were % organic phase composition, column temperature, and flow rate. The critical quality attributes investigated were retention time and theoretical plates. Results: Chromatographic separation was accomplished on Agilent Zorbax Eclipse C18 (150×4.6 mm, 5 μm) column. The optimized and predicted data from Design Expert software consist of mobile phase 0.1 % orthophosphoric acid (46.3%): Acetonitrile (53.7%), pumped at a flow rate of 0.91 ml/min at 32.6°C gave the highest desirability function of 1. The retention time of the drug was found to be 2.85 min. The developed method was validated as per the ICH Q2 (R1) guidelines. Conclusion: Based on the analysis of variance values, the selected models were found to be significant with p<0.05. The results of the validation parameters were within the acceptable limit. The stability of the drug was examined under different stress conditions forcibly and significant degradation was found in acidic condition.

scholarly journals Application of Elements of Quality by Design to Development and Optimization of HPLC Method for Fingolimod

2021 ◽  
pp. 318-328
Author(s):  
Siddique Akber Ansari ◽  
Mrinmayee Deshpande ◽  
Jaiprakash N. Sangshetti ◽  
Sarfaraz Ahmed ◽  
Irfan Aamer Ansari
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Method Development ◽  
Quality By Design ◽  
Hplc Method ◽  
Contour Plots ◽  
Target Profile ◽  
Quality By Design Approach ◽  
Actual Response

Purpose: A HPLC method for Fingolimod was developed using a Quality by Design concept. QbD has gained importance in recent times due to regulatory requirements. Actual study was started after determination of target profile and qualification of instrument. Methods: Separation was carried on a Grace C-8 column (4.6 x 250 mm, 5-μm particle size).The composition of mobile phase was methanol and 20 mM ammonium formate buffer of pH5.8 in gradient mode HPLC method development is affected by critical factors like pH, flow rate and mobile phase composition. Results: To study the effects of these three factors on USP tailing, Box Behnken optimization model was applied. Desirability of the model was set at Tailing less than 1.2.Analysis of results was done using surface diagrams. Verification of Software generated results was done by taking six replicates of the run. Thus developed and optimised method was Finally validated as per ICH guideline. Conclusion: A Quality by Design approach has been successfully utilised in method development of the Fingolimod in bulk. All key aspect of QbD were tried to be implemented in said study. Systematic approach was utilized for method development which includes beginning with determination of target profile characteristics, instrument qualification, risk assessment, design of experiment and validation. Three factors i.e. Ph, flow rate and methanol concentration were analysed for their effect on USP tailing as a responce. Interaction and quadratic effect of the factors were studied with least possible runs by using Box Behnken model. Response surface diagrams and contour plots were studied for coming to conclusion which factors are affecting response and their limits were recorded. Optimum run condition was obtained; Replicates of run having optimized condition were taken to confirm the predicted response with actual response.

scholarly journals Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach

Chemosensors ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 172
Author(s):  
João Basso ◽  
Maria Luísa Ramos ◽  
Alberto Pais ◽  
Rui Vitorino ◽  
Ana Fortuna ◽  
...  
Keyword(s):  
Quality By Design ◽  
Hplc Method ◽  
Analytical Quality ◽  
Optimal Method ◽  
Method Performance ◽  
Effect Analysis ◽  
Quality By Design Approach ◽  
Face Centered ◽  
Definition Of ◽  
Copper Diethyldithiocarbamate

An Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect analysis (FMEA)) was employed to identify the critical method parameters (CMPs) with an extensive impact on method performance. The behavior of the CMPs (flow rate and mobile phase composition) was further characterized by experimental design, resorting to a face-centered central composite design (FcCCD). Statistical modeling, response surface analysis, and Monte Carlo simulations led to the definition of the Method Operable Design Region (MODR), associated with a negligible risk of failing the predefined CAA specifications. The optimal method was validated according to international regulatory recommendations. Apart from guaranteeing linearity, accuracy, precision, specificity, robustness, and stability, these conditions were found to be suitable for analysis using a different HPLC column and equipment. In a nutshell, the development and optimization strategies, under the comprehensive framework of AQbD, provided an effective, simple, rapid, reliable, and flexible method for routine analysis of the compounds in research or industrial environments.

Development, Validation and Application of HPLC Method for Metformin in Rabbit Plasma

2019 ◽  
Vol 15 (6) ◽  
pp. 574-579
Author(s):  
Muhammad Ubaid ◽  
Mahmood Ahmad ◽  
Farhan Ahmad Khan ◽  
Ghulam Murtaza
Keyword(s):  
Flow Rate ◽  
Present Method ◽  
Mobile Phase ◽  
Hplc Method ◽  
Plasma Samples ◽  
Rabbit Plasma ◽  
Uv Detector ◽  
Reverse Phase ◽  
T Values ◽  
Pharmacokinetic Evaluation

Objective:This study was aimed at conducting a pharmacokinetic evaluation of metformin in rabbit plasma samples using rapid and sensitive HPLC method and UV detection.Methods:Acetonitrile was used for protein precipitation in the preparation of plasma samples. Reverse phase chromatography technique with silica gel column (250 mm × 4.6 mm, 5 μm) at 30°was used for the separation purpose. Methanol and phosphate buffer (pH 3.2) mixture was used as a mobile phase with flow rate 0.8 ml/min. The wavelength of UV detector was adjusted at 240 nm.Results:The calibration curve was linear in a range of 0.1-1 µg/ml with R² = 0.9982. The precision (RSD, %) values were less than 2%, whereas, accuracy of method was higher than 92.37 %. The percentage recovery values ranged between 90.14 % and 94.97 %. LOD and LOQ values were 25 ng/ml and 60 ng/ml, respectively. Cmax and AUC0-t values were found to be 1154.67 ± 243.37 ng/ml and 7281.83 ± 210.84 ng/ml.h, respectively after treating rabbits with a formulation containing 250 mg metformin.Conclusion:Based on the above findings, it can be concluded that present method is simple, precise, rapid, accurate and specific and thus, can be efficiently used for the pharmacokinetic study of metformin.

scholarly journals Box-Behnken Assisted Validation and Optimization of an RP-HPLC Method for Simultaneous Determination of Domperidone and Lansoprazole

Separations ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Mohd Afzal ◽  
Mohd. Muddassir ◽  
Abdullah Alarifi ◽  
Mohammed Tahir Ansari
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Box Behnken Design ◽  
Rp Hplc ◽  
System Suitability ◽  
Method Optimization ◽  
Key Variables

A highly specific, accurate, and simple RP-HPLC technique was developed for the real-time quantification of domperidone (DOMP) and lansoprazole (LANS) in commercial formulations. Chromatographic studies were performed using a Luna C8(2), 5 μm, 100Å, column (250 × 4.6 mm, Phenomenex) with a mobile phase composed of acetonitrile/2 mM ammonium acetate (51:49 v/v), pH 6.7. The flow rate was 1 mL·min−1 with UV detection at 289 nm. Linearity was observed within the range of 4–36 µg·mL−1 for domperidone and 2–18 µg·mL−1 for lansoprazole. Method optimization was achieved using Box-Behnken design software, in which three key variables were examined, namely, the flow rate (A), the composition of the mobile phase (B), and the pH (C). The retention time (Y1 and Y3) and the peak area (Y2 and Y4) were taken as the response parameters. We observed that slight alterations in the mobile phase and the flow rate influenced the outcome, whereas the pH exerted no effect. Method validation featured various ICH parameters including linearity, limit of detection (LOD), accuracy, precision, ruggedness, robustness, stability, and system suitability. This method is potentially useful for the analysis of commercial formulations and laboratory preparations.

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