oncepts in development of fast, simple, stability indicating HPLC method for analysis of atorvastatin related compounds in tablets

New, fast, simple and mild conditioned High Performance Liquid Chromatography (HPLC) method for determination of atorvastatin and its 7 main specified impurities, as well as unspecified impurities that might possibly appear, was developed. Chromatographic runs last between 25 and 40 minutes, with simple stepwise gradient elution. The main accent in our method development strategy was focused on mobile phase, composed of simple binary system composed of phosphate buffer and acetonitrile, at pH 4.1, without use of tetrahydrofuran, ion-pair reagents, trifluoroacetic acid and other modifiers with high Ultraviolet (UV) cut-off like absorptive acetate or formiate buffers or amines. With our concept of mobile phase, different columns from myriad were tested, with different efficiency, dimensions and properties, which resulted in different separation efficiency and run time. The best results, concerning essential critical peak resolution, run time length including column preparation and equilibration and column backpressure, were achieved with: YMC C18 Triart 150mm x 4.6mm, 3µm (YMC America, Inc.), afterwards with Nucleodur 100-3-C18ec 250mm x 4.6mm, 3µm (Macherey-Nagel GmbH & Co., Germany), Waters Symmetry C18 250mm x 4.6mm, 5µm (Waters, USA) and Superspher C18e 125mm x 4mm, 4µm (Merck, Darmstadt, Germany). All this columns achieve excellent results regarding obligated critical resolution between atorvastatin impurity B and atorvastatin (according to European Pharmacopoeia),1 or in some cases between atorvastatin impurity B and atorvastatin impurity C, to be minimum about 1.5, in both cases.

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Method Development and Validation for Quantification of Potential Genotoxic Impurity, PyCl in Lansoprazole Hydrochloride using Liquid Chromatography Combined with Mass Spectrometry

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23135 ◽

2021 ◽

Vol 33 (5) ◽

pp. 1165-1168

Author(s):

C. Purushotham Reddy ◽

G. Venkateswara Rao ◽

K. Ramakrishna ◽

K.M.V. Narayana Rao

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Mobile Phase ◽

High Performance ◽

Method Development ◽

Limit Of Detection ◽

Gradient Elution ◽

Solution Stability ◽

Selective Ion Monitoring ◽

Acquity Uplc

A sensitive and robust high performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of potential genotoxic impurity (PGI), 2-(chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)-pyridine hydrochloride (PyCl) in lansoprazole as per ICH Q2 guideline. In this method, PyCl and lansoprazole were well-separated from each other on Acquity UPLC BEH-C18 column (50 × 4.6 mm × 1.7 μ) in a gradient elution mode with the mobile phase consisting of 0.1% formic acid in water (mobile phase-A) and acetonitrile (mobile phase-B) at a flow rate of 0.4 mL/min. For the quantitation of Py-Cl, selective ion monitoring (SIM) mode was used with m/z 240 ion in LC-MS method. The validated method was found to be precise, accurate and linear from the range of LOQ level to 150% with respect to sample concentration and the correlation co-efficient was found to be 0.998. Limit of detection (LOD) and limit of quantifications (LOQ) were found to be 0.000012 and 0.000004 mg/mL, respectively. The validated method was found to be sensitive and the recoveries were found to be well within the range from 83.4% to 95.9% for Py-Cl. Further, the solution stability was also established as the same were found to be stable upto 24 h.

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RP-HPLC method development and validation for simultaneous estimation of efonidipine hydrochloride ethanolate and telmisartan in their synthetic mixture

International Journal of Pharmaceutics and Drug Analysis ◽

10.47957/ijpda.v9i3.480 ◽

2021 ◽

pp. 190-195

Author(s):

Grishma H Patel ◽

Shreya D Adeshra ◽

Dhananjay B Meshram

Keyword(s):

Mobile Phase ◽

High Performance ◽

Method Development ◽

High Performance Liquid Chromatographic ◽

Reversed Phase ◽

Hplc Method ◽

Simultaneous Estimation ◽

Quality Control Laboratory ◽

Efficient Option ◽

Liquid Chromatographic

A Novel, selective, accurate and rapid Reversed Phase High Performance Liquid Chromatographic (RPHPLC) method for the analysis of Efonidipine Hydrochloride Ethanolate and Telmisartan in binary mixture has been developed and validated. The chromatographic system consisted of a Phenomenex Kinetex ® 5µ C18 Size: 150 * 4.6mm column and the separation was achieved by using ambient temperature with a mobile phase containing mobile Phase Acetonitrile:25mM Phosphate Buffer pH 4.9 (45:55). The samples were monitored at 253 nm for detection at a flow rate of 1.0 mL/min and the retention time was about 7.77 and 4.10 mins for Efonidipine Hydrochloride Ehanolate and Telmisartan respectively. The calibration curve was linear over the concentration range 5-30 and 10-60 ?g/mL for Efonidipine Hydrochloride Ehanolate and Telmisartan respectively. The proposed method is accurate in the range of 99.75% - 100.10% recovery and precise (%RSD of intraday variation and % RSD of inter day variation were found to be within the acceptance criteria). Therefore, this method can be used as a more convenient and efficient option for the analysis of Efonidipine Hydrochloride Ehanolate and Telmisartan in Quality control laboratory.

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Development and Validation of RP-HPLC Method for Desoximetasone in Bulk and Cream Formulation

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i3.2630 ◽

2019 ◽

Vol 9 (3) ◽

pp. 154-159

Author(s):

Ashish Gorle ◽

Jayashri Mahajan ◽

Prathamesh Bhave

Keyword(s):

Method Validation ◽

Mobile Phase ◽

High Performance ◽

Gradient Elution ◽

Hplc Method ◽

Topical Steroids ◽

Cream Formulation ◽

Rp Hplc ◽

Validation Parameters ◽

Development And Validation

Desoximetasone chemically is 9-fluoro-IIβ21-dihydroxy-I6a-methylpregna-I.4-diene-3.The precise mechanism of the anti-inflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. So, in present investigation chromatographic methods were developing use RP-HPLC for estimation of Desoximetasone in bulk and in cream formulation and method validation according to ICH guidelines. The main objective of this study was to develop a simple and reproducible method for desoximetasone by Reverse Phase High Performance Liquid Chromatography (RP-HPLC). In this work the desoximetasone separation was carried out by using C18 cosmosile column (250mmx4.6mm particle size 5µm). By using 0.1% orthrophosphoric acid pH adjusted up to 3 at uv detection of 240nm.The mobile phase was used at various ratio for gradient elution the ratio of mobile phase was 20:80 v/v. Methanol and water used for mobile phase and flow rate was being set at 1mL/min. The linearity of proposed method was found in range of r =0.9989. Statistically validation parameters such as linearity, accuracy, precision, LOD and LOQ were checked. Keywords: Desoximetasone, RP-HPLC, Method validation.

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Stereospecific Determination of Sertraline and its Impurities in Bulk Drug Using Cyclodextrins as a Chiral Selector

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190312164301 ◽

2020 ◽

Vol 16 (7) ◽

pp. 823-830 ◽

Cited By ~ 1

Author(s):

Navjot Kaur Sandhu ◽

Durga Das Angehore ◽

Neeraj Upmanyu ◽

Pawan K. Porwal

Keyword(s):

Mobile Phase ◽

High Performance ◽

Method Development ◽

High Performance Liquid Chromatographic ◽

Hplc Method ◽

Related Substances ◽

System Suitability ◽

Bulk Drug ◽

Liquid Chromatographic

Background: Sertraline Hydrochloride, an oral anti-depressant, has two chiral centers and its cis enantiomers and trans diasteromers are defined as related substances by United State Pharmacopoeia and British Pharmacopoeia. Introduction: A selective, stereospecific and economical high performance liquid chromatographic (HPLC) method was developed for the determination of sertraline enantiomeric forms. The HPLC-UV method was developed and optimized in the terms of system suitability parameters. Methods: The elution was made using a mixture of -cyclodextrin (-CD) and hydroxypropyl - cyclodextrin (HP -CD). Analysis was performed on a Zorbax SB C-18 column (250 x 4.6mm), 5μ with the mobile phase consisting of 170mM KH2PO4 containing -CD and HP -CD (pH: 3.0 with dil. H3PO4) and acetonitrile (75:25, v/v). Flow rate was kept at 1.0mL/min and the detection was carried out by UV at 220nm. Enantio-separation for sertraline was carried out using two different CDs (β-CD and HP β- CD) at different concentrations in the mobile phase. Results: Complete resolution of all the four isomers was achieved using 9mM β-CD and 15mM HP β- CD in the mobile phase. The development was optimized using central composite quadric model, where concentration of -CD and HP -CD were varied and resolution between trans diastereomeric impurities was calculated as a response. Conclusion: Resolution between any pair of isomers was found to be more than 2. Method development and optimization leading to the best resolution between the isomers of sertraline is described in detail.

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Method Development and Validation of Salmeterol xinofoate by HPLC

International Journal of Pharmaceutical Sciences and Medicine ◽

10.47760/ijpsm.2021.v06i06.006 ◽

2021 ◽

Vol 6 (6) ◽

pp. 52-63

Author(s):

Sahebrao H. Shembade ◽

Sagar S. Landage ◽

Ashapak M. Tamboli ◽

Ritesh S. Bhate ◽

Kaustubh V. Gavali ◽

...

Keyword(s):

Mobile Phase ◽

High Performance ◽

Method Development ◽

Quantitative Estimation ◽

Hplc Method ◽

Chromatography Method ◽

Ich Guidelines ◽

Method Development And Validation ◽

Liquid Chromatography Method ◽

Development And Validation

A rapid and precise high performance liquid chromatography method has been developed for the validation of Salmeterol xinofoate in its pure dosage form. The separation was carried out on Agilent Zorbax Bonus RP- (250mm ×4.6mm 5μ) column with a mobile phase consisting of 0.1% Formic acid: Acetonitrile in the ratio of 64:36 v/v as a mobile phase and flow rate is 1ml/min. The detection was carried out at wavelength 234nm. The column thermostatically controlled at 30℃. The retention time of Salmeterol was found to be 1.96 min. The Salmeterol xinofoate followed linearity in the concentration range of 40-60μg/mL with r2= 0.999. The developed method was validated for sensitivity, accuracy and precision. The sample was scanned from 200- 400nm with PDA detector. The % recovery of sample was found to be. The LOD and LOQ of the Salmeterol xinofoate was found to be 2.67μg/ml and 8.08μg/ml respectively. The suitability of this HPLC method for quantitative estimation of Salmeterol xinofoate was proved by validation by the requirements of ICH guidelines.

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QBD APPROACH TO ANALYTICAL METHOD DEVELOPMENT AND ITS VALIDATION FOR ESTIMATION OF LENVATINIB IN BULK AND PHARMACEUTICAL FORMULATION

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i5.41786 ◽

2021 ◽

pp. 183-188

Author(s):

SACHIN A. BABAR ◽

SUDHAKAR L. PADWAL

Keyword(s):

Central Composite Design ◽

Mobile Phase ◽

High Performance ◽

Method Development ◽

Hplc Method ◽

Factor Screening ◽

Pharmaceutical Dosage Forms ◽

Rp Hplc ◽

Chromatographic Condition ◽

Central Composite

Objective: The objective of this research was to develop a simple, very rapid, sensitive, accurate, precise reverse phase High-Performance Liquid Chromatography (RP-HPLC) technique for the estimation of Lenvatinib in bulk and its dosage form. Methods: To perform this study, we employed a central composite design (CCD) to make method robust and effective to create chromatographic database. The factor screening studies were performed using 2-factor 10-runs. The factors were selected as the mobile phase ratio and buffer pH. Results: The desirability value of the optimized model was found to be 0.869 and The optimized chromatographic condition was achieved on Enable C18 analytical column with 0.01M Ammonium acetate buffer pH 3.84: methanol (33.17:66.83 v/v) as the mobile phase and flow rate of 1 ml min-1 and detection wavelength was set to 240 nm. The retention time of Lenvatinib was found to be 5.122 min. Linearity was established for Lenvatinib in the range of 10-50 µg/ml with a correlation coefficient (r2=0.9995). The accuracy values were found to be in the range of 98–102%. Intraday precision and Interday precision were in prescribed (Less than 0.98% RSD). Robustness was found to be less than 1.22% RSD. Conclusion: The proposed method was useful for best analysis of Lenvatinib in Bulk pharmaceutical dosage forms. Central Composite Design was an effective tool for the proposed RP-HPLC method.

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Challenges of HPLC Method Development and Validation for the Assay of Bemotrizinol from Complex Matrix in Cosmeceutical Preparation

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.11.3.2 ◽

2020 ◽

Vol 11 (03) ◽

pp. 310-316

Author(s):

Kallol S Jana ◽

Beduin Mahanti

Keyword(s):

Mobile Phase ◽

High Performance ◽

Method Development ◽

Limit Of Detection ◽

Linear Regression Analysis ◽

Cost Effective ◽

Analysis Data ◽

Hplc Method ◽

Limit Of Quantification ◽

Relative Standard

A simple high performance liquid chromatography (HPLC) method was developed for the assay of bemotrizinol (Tinosorb-S) from the complex pharmaceutical cosmetics matrix. Unlike the existing methods, the proposed mobile phase used in this method is very simple and excluding buffer. The use of buffer reducing column longevity and also a time-consuming process which increases the cost of analysis. To overcome all the referred problems, the present article was developed and validated as per International Council for Harmonization (ICH) guidelines. The reverse-phase chromatography was performed on Shimadzu model no. SPD-M10A VP with LC solution software, μBondapack (3.9 × 300 mm, 10-micron particle size) column with methanol (100%) as mobile phase at a flow rate 2.5 mL per minutes and UV detection at 254 nm. The retention time of bemotrizinol was found in 17.599 minutes, and the linear regression analysis data for the calibration plots showed a good linear relationship in the concentration range 70 to 130 μg/mL. The value of the correlation coefficient, slope, and intercept were 0.996, 7,715, and 15,320, respectively. The limit of quantification (LoQ) and limit of detection (LoD) were found to be 1.32 and 0.44, respectively. The relative standard deviation (RSD) for intra-day sample A 1.0858, sample B 0.8859, and inter-day sample A 0.9921, sample B 0.967 which were found to be lesser than 2%. The developed method was validated with regard to linearity, accuracy, precision, selectivity, and robustness, and the method was found to be simple, cost-effective, precise, accurate, linear, and specific for the successful identification and determination of bemotrizinol in pharmaceutical cosmetic preparation.

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Analytical QbD: Designing Space for HPLC Method Operable Region for Estimation of Preservatives in Herbal Formulation

Current Pharmaceutical Analysis ◽

10.2174/1573412914666171218151224 ◽

2019 ◽

Vol 15 (2) ◽

pp. 152-164

Author(s):

Kalpana Patel ◽

Hinal Jitendrabhai Patel ◽

Jenee Christian ◽

Lal Hingorani ◽

Tejal Gandhi

Keyword(s):

Retention Time ◽

Mobile Phase ◽

High Performance ◽

Method Development ◽

Orthophosphoric Acid ◽

Hplc Method ◽

Good Resolution ◽

Method Performance ◽

Herbal Formulation ◽

Critical Method

Background: Quantification of preservatives in herbal formulation, simultaneously by high performance liquid chromatography analysis is very complex and involves series of steps including sample preparation, selection of suitable mobile phase and its validation for routine applications. Introduction: Application of Quality by Design (QbD) in the development of novel, simple, accurate and precise RP-HPLC method for concurrent quantification of quaternary preservatives in herbal formulation, focusses on development of robust method. Methods: Isocratic analysis was carried out using C18 column at 231 nm. Risk assessment studies were executed to determine the critical method parameters which were defined as acetonitrile volume in the mobile phase, volume of injection and orthophosphoric acid concentration in the mobile phase. The effect of the critical method parameters on critical method attributes, i.e. retention time, resolution and chromatographic optimization function was further evaluated by means of central composite design and the optimal conditions were determined through derringer’s desirability approach of multi-criteria decision making technique. Results: The method was statistically validated according to ICH guidelines having good resolution using optimized mobile phase, acetonitrile: 0.11% orthophosphoric acid in water (12.30: 87.70 % v/v) giving acceptable retention time i.e. 3.7128 ± 0.0138 of bronopol, 4.5106 ± 0.00542 of sodium propyl paraben, 10.7228 ± 0.029 of sodium benzoate and 12.252 ± 0.027 of sodium methyl paraben. Conclusion: Hence, the QbD based method development assisted in generating a design space with knowledge of all method performance characteristics leading to a better understanding of the method, and achieving desirable method quality.

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RP-HPLC METHOD DEVELOPMENT AND VALIDATION OF MACITENTAN WITH ITS KNOWN AND UNKNOWN DEGRADATION IMPURITIES IN ITS TABLET DOSAGE FORM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.26211 ◽

2018 ◽

Vol 10 (5) ◽

pp. 81

Author(s):

Jahanvee K. Trivedi ◽

Chirag J. Patel ◽

M. M. Patel

Keyword(s):

Mobile Phase ◽

Method Development ◽

Gradient Elution ◽

Hplc Method ◽

Forced Degradation ◽

Rp Hplc ◽

Extensive Degradation ◽

As Stress ◽

Hplc Method Development ◽

Tablet Dosage

Objective: To develop and validate macitentan with its known and unknown degradation impurities in its tablet dosage form.Methods: The RP-HPLC method for macitentan and its impurities was developed and three potential degradation impurities MCA-02, MCA-01 and degradation impurity and N-propyl derivative and N-N dimethyl derivative process impurities were separated. Chromatographic separation was achieved within 70 min on Inertsil C8 (250*4.6 mm, 5 µm) column, Using mobile phase A [Ammonium acetate (ph 4.5 adjusted with glacial acetic acid)] and mobile phase B acetonitrile in gradient elution. Other hplc parameter which was optimized flow rate 1.5 ml/min, detection wavelength 266 nm, column oven temperature 30 ° C and injection volume 20μl. macitentan was subjected to forced degradation also known as stress testing. It was validated as per ICH guidelines.Results: The drug showed extensive degradation in acidic and basic conditions, a slight degradation in oxidative condition. The developed method was statistically validated for linearity (0.45-2.25 ppm). The result of precision (%RSD<5), robustness, LOD(0.15 ppm) and LOQ(0.45 ppm) are well within limits.% Recovery at LOQ, 50%, 100% and 150% was found to be within limit 80-120 %.Conclusion: RP-HPLC method was successfully developed with satisfactory separation of macitentan and its impurities. The proposed method was found to be specific, accurate, precise and robust can be used for estimation of macitentan and its impurities and can be successfully employed in the routine analysis of macitentan.

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A NEW STABILITY-INDICATING RP-HPLC METHOD FOR DETERMINATION OF CURCUMIN: AN APPLICATION TO NANOPARTICULATE FORMULATION

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.14473 ◽

2016 ◽

Vol 8 (12) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Suchitra Panigrahi ◽

Rajashree Hirlekar

Keyword(s):

High Performance ◽

Method Development ◽

Limit Of Detection ◽

Pharmaceutical Formulations ◽

High Performance Liquid Chromatographic ◽

Hplc Method ◽

Stability Indicating ◽

Limit Of Quantitation ◽

Run Time

Objective: The present study was aimed to develop a rapid, accurate, linear, sensitive and stability-indicating high performance liquid chromatographic method for determination of curcumin and to implement the developed method for the estimation of curcumin in the nanoparticulate formulation.Methods: Method development was performed using various solvent, buffer-solvent ratios, at different flow rates for better resolution and to decrease the run time. The developed method was validated in accordance with the international conference on harmonization (ICH) guidelines. The developed method was implemented to estimate the amount of curcumin in the curcumin-nanoparticulate formulation.Results: The optimum chromatographic conditions with adequate resolution for curcumin (16.10 min) was achieved when the separation was carried using C18 column at ambient temperature with an isocratic elution mode of mobile phase composed of a degassed mixture of phosphate buffer pH 3 and acetonitrile (50:50 v/v) at 1.0 ml/min flow rate with a total run time of 20 min. The developed method was validated for system suitability, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), linearity and range. The LOD and LOQ were found to be 0.018 and 0.056 μg/ml respectively, which indicates that the method was sensitive, and can detect and quantify at lower levels of curcumin. Linearity range was from 5-15 μg/ml for curcumin with regression coefficient 0.997 indicates that at this concentration range curcumin was highly linear. Percent assay of curcumin was found to be 98.7% and curcumin recovered was found to be 0.78 mg which are estimated by using the developed method.Conclusion: The developed analytical method is simple, precise, and reproducible and thus can be used for stability-indicating analysis of curcumin in pharmaceutical formulations.

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