scholarly journals Development and optimization of HPLC-MS method for simultaneous determination of four terpene trilactones in Ginkgo biloba leaf extracts based on Quality by Design principles

2020 ◽  
Author(s):  
Sijie Zhang ◽  
Linlin Wu ◽  
Xiaoping Wang ◽  
Xingchu Gong ◽  
Haibin Qu
Keyword(s):  
Flow Rate ◽  
Ginkgo Biloba ◽  
Control Strategy ◽  
Mobile Phase ◽  
Quality By Design ◽  
Design Space ◽  
Analytical Control ◽  
Screening Experiments ◽  
Critical Method ◽  
Terpene Trilactones

Abstract Background Ginkgo biloba leaf extract (EGBL) is one of the most commonly used and most studied herbal medicines around the world. Taking into account that previously reported HPLC-ELSD methods for terpene trilactones determination in EGBL are time-consuming with complicated sample preparation, it is reasonable and meaningful to developing a simple, sensitive and robust HPLC-MS method based on a novel analytical quality by design (AQbD) approach. Methods Firstly, analytical target profile (ATP) and systematic risk analysis were carried out to identify potential critical method attributes (CMAs) and critical method parameters (CMPs). Secondly, CMPs were identified using a standard partial regression coefficient method. Thirdly, Box-Behnken design (BBD) was employed to establish the quantitative relationship between CMAs and CMPs. Fourthly, the Monte Carlo simulation method was used to build hypercube design space. Then, the verification experiments were performed. Fifthly, the optimized method was validated and utilized. Finally, the paired t test was used to compare the developed method with HPLC-ELSD. Results After the screening experiments, flow rate of mobile phase, the proportion of formic acid in the mobile phase, gas flow rate and gas temperature were identified as CMPs. Models to quantitatively describe the relationship between CMAs and CMPs were built. The operational hypercube design spaces of the HPLC-MS method for terpene trilactones analysis in EGBL were successfully calculated and found to be robust, which led to the analytical control strategy. The verification experiments were successfully performed within the design space and model was found to be accurate. The method had been successfully used for quality analysis of development batches of EGBL and obtained almost identical results to data determinated using HPLC. Conclusions In this work, an analytical control strategy for HPLC-MS method for terpene trilactones analysis in EGBL was developed using AQbD concepts, which is promising for application to other Chinese medicines. The developed HPLC-MS method is an alternative method for quantification of terpene trilactones in commercial EGBL and will be applicable throughout the life cycle of the product.

scholarly journals Development and Validation of a Ultra Flow Liquid Chromatography Method for the Assay of Boceprevir Using a Quality-by-Design Approach

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 3023-3032
Author(s):  
Manish Majumder ◽  
Ramesh B ◽  
Minaketan Tripathy
Keyword(s):  
Risk Assessment ◽  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Quality Attributes ◽  
Assay Method ◽  
Chromatography Method ◽  
Critical Quality Attributes ◽  
Critical Method ◽  
Quality By Design Approach

Quality by design guided. The assay method of Boceprevir is developed in accordance with ICH Q8(R2) guideline with due validation. .In this process, the Target analytical profile (TAP) of the drug was set and critical method parameters (CMP) were investigated by systematic risk assessment experimentation to control critical Quality Attributes (CQA). In this, A Cause Effect Risk Assessment Matrix with Control-Noise-Experiment (CNX) is used for identifying the high-risk variables i.e Percentage of Organic Modifier (% methanol), pH of the Buffer and flow rate of the mobile phase. The surface response methodology was applied to optimize the critical method parameters (CMP) as well as Critical Quality Attributes (CQA) to find out the Design space of the method. The Optimum assay method condition was mobile phase Acetate Buffer (50mM) pH 5.4: Methanol (11:89), Flow rate: 0.9 ml/min, Lambda Max: 207. The separation was achieved in the Eclip Plus C-18 column (250 × 4.6 mm, 5μm) at ambient temperature. The retention time of Boceprevir was found to be 4.2 min. The method evaluation was performed according to the (Q2R1) ICH guideline.

scholarly journals Quality by Design Approach for Development and Validation of Stability Indicating RP-HPLC Method for Fosaprepitant Dimeglumine

2020 ◽  
Vol 32 (9) ◽  
pp. 2158-2164
Author(s):  
JALIL K. SHAIKH ◽  
MAZAHAR FAROOQUI ◽  
UMMUL KHAIR ASEMA SYED
Keyword(s):  
Mobile Phase ◽  
Quality By Design ◽  
Orthophosphoric Acid ◽  
Design Space ◽  
Acid Base ◽  
Column Temperature ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Hydrogen Sulphate ◽  
Quality By Design Approach

Quality by design approach has been used to develop simple, rapid, sensitive gradient RP-HPLC stability indicating method for fosaprepitant dimeglumine and its related impurities. The chromatographic method has been developed by using symmetry shield RP-18 (250 mm × 4.6 mm; 5 μm) column maintained at column temperature of 20 ºC. The mobile phase-A consisted of water and acetonitrile (800:200, v/v), added 2 mL of orthophosphoric acid and 0.17 g of tetrabutylammonium hydrogen sulphate. The mobile phase-B consisted of water and acetonitrile (200:800, v/v), added 2 mL of orthophosphoric acid and 0.17 g of tetrabutylammonium hydrogen sulphate. Gradient program was executed as time (min)/% MP-A: 0/80, 3/80, 12/40, 20/20, 24/20, 25/80, and 30/80. The UV detection was carried out at wavelength 210 nm and 20 μL of sample was injected. Sample cooler was maintained at 5 ºC. Stability of fosaprepitant dimeglumine sample was investigated in different stress condition as acid, base, oxidation, thermal, humidity and photolytic. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and solvent were identified based on the behaviour of each stationary phase with fosaprepitant dimeglumine and its impurities using each buffer and solvent. Total 18 experiments were performed to find out the best experimental condition. The optimization was done for secondary influential parameters like column temperature, gradient program, using six experiments to examine multifactorial effects of system suitability parameters and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was accurate. Drug showed unstable behaviour under acid, base, oxidation, thermal, and humidity conditions. Apripetant was found as major degradation impurity. The method was validated as per ICH guideline for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, accuracy, precision, ruggedness and robustness. Correlation coefficient is about 0.999 for all impurities, recovery is between 90% to 103% at all level. LOD value of each impurity is less than 0.01% w/w. DOE statistically based experimental designs proved to be an important approach in optimizing selectivity-controlling parameters for the organic impurities determination in FD API. The method was found to be specific, linear, accurate, precise and robust. The peak purity test results confirmed that the fosaprepitant dimeglumine peak was homogenous in all stress samples and the mass balance was found to be more than 99%, thus proving the stability indicating power of the method. Present method is found to be suitable for routine analysis in quality control laboratory.

scholarly journals QbD Approach for the Development and Validation of RP-UHPLC Method for Quantitation of Vildagliptin

2017 ◽  
Vol 16 (1) ◽  
pp. 107-117
Author(s):  
Sharifa Sultana ◽  
Uttom Kumar ◽  
Md Shahadat Hossain ◽  
Dilshad Noor Lira ◽  
Abu Shara Shamsur Rouf
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Quality By Design ◽  
Response Surfaces ◽  
Routine Analysis ◽  
Pharmaceutical Dosage Forms ◽  
Independent Variables ◽  
Two Factors ◽  
Bulk Drug ◽  
Development And Validation

The present work describes a quality by design (QbD)-based rapid, simple, precise and robust RPUHPLC method for the routine analysis of vildagliptin in bulk drug and in pharmaceutical dosage forms. Chromatographic separation was achieved by a X-bridge C18 column with isocratic elution of mobile phase containing mixture of phosphate buffer (pH 6.8) and acetonitrile in the ratio of 67:33(v/v). The flow rate was 1.0 ml/min and the detection was done at 239 nm with photo-diode array plus (PDA+) detector. The optimization of chromatographic method was carried out by QbD approach using design of experiments (DoE). Two factors utilized for the experimental design of the method were (i) independent variables which comprise percentages of acetonitrile in mobile phase and flow rate and (ii) co-variates which include the retention time, tailing factor and theoretical plates. This design was statistically analyzed by ANOVA, normal plot of residual, box-cox plot for power transform, perturbation, counter plot and 3D response surfaces plots. This was further validated as per the requirements of ICHQ2B guidelines for linearity, LOD, LOQ, accuracy, precision, specificity and robustness. The results showed that proposed method is simple, sensitive and highly robust for routine analysis of vildagliptin.Dhaka Univ. J. Pharm. Sci. 16(1): 107-117, 2017 (June)

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 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

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.

Simultaneous Separation and Quantification of Vitamins by Microemulsion Liquid Chromatography

2020 ◽  
Vol 58 (7) ◽  
pp. 591-599
Author(s):  
Tongtong Xu ◽  
Hongxing Wu ◽  
Aini Zheng ◽  
Nuojun Yu ◽  
Ning Li
Keyword(s):  
Liquid Chromatography ◽  
Flow Rate ◽  
Mobile Phase ◽  
High Performance ◽  
Sodium Dodecyl ◽  
Gradient Elution ◽  
Simple Method ◽  
Water Solvent ◽  
Screening Experiments ◽  
Fat Soluble Vitamins

Abstract Microemulsion eluents have been found to have excellent potential uses in high-performance liquid chromatography (HPLC). Here, a novel, environmentally benign and simple method using concentration/flow-rate double-gradient elution using a microemulsion eluent was used to separate water- and fat-soluble vitamins simultaneously and rapidly. Preliminary screening experiments were performed to determine the optimum column type, surfactant concentration, co-surfactant to surfactant ratio, oil, mobile phase pH and microemulsion concentration. The resolution and analysis time were simultaneously optimized using concentration/flow-rate double-gradient elution. The optimized method simultaneously separated water- and fat-soluble vitamins using a Venusil ASB C8 column and a combination of isocratic and linear gradient elution modes using a microemulsion mobile phase (solvent A) consisting of 3.5% (w/w) sodium dodecyl sulfate, 10.5% (w/w) n-butanol, 0.8% (w/w) n-octanol and 85.2% (w/w) water and water (solvent B) at pH 2.50. The optimum detection wavelength was 283 nm. The method was validated and used to analyze a solid pharmaceutical sample.

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