Analytical Stability-Indicating Methods for Alogliptin in Tablets by LC–CAD and LC–UV

2017 ◽  
Vol 100 (2) ◽  
pp. 400-405 ◽  
Author(s):  
Charise Dallazem Bertol ◽  
Maria Tereza Friedrich ◽  
Graciela Carlos ◽  
Pedro Eduardo Froehlich
Keyword(s):  
Mobile Phase ◽  
Ammonium Acetate ◽  
Degradation Products ◽  
Uv Detector ◽  
Pareto Chart ◽  
Ammonium Acetate Buffer ◽  
Stability Indicating ◽  
Analytical Stability ◽  
Charged Aerosol ◽  
Charged Aerosol Detector

Abstract Stability-indicating LC methods using a UV detector and a charged aerosol detector (CAD) simultaneously were validated for the assessment of alogliptin (ALG) in tablets. The analysis was performed on a C8 column (250 × 4.6 mm, 5 μm) at a flow of 0.8 mL/min, using acetonitrile–10 mM ammonium acetate buffer (pH 3.5; 90 + 10, v/v) as mobile phase and UV detection at 275 nm. Validation followed the International Conference on Harmonization guidelines. The method was linear over the range of 25–200 μg/mL. Normality of the residuals showed a normal distribution, no autocorrelation, and homoscedasticity. LODs were 6.25 and 2.65 µg/mL and LOQs were 20.85 and 8.84 µg/mL for the CAD and the UV detector, respectively. The methods were precise and accurate. Excipients and degradation products did not interfere in the methods in studies of specificity. None of the factors studied in the analysis of robustness had a significanteffect on the quantification of the ALG by the Pareto chart. The results of the assay obtained with LC–CAD and LC–UV were similar. The methods could be considered interchangeable and stability-indicating, and can be applied as an appropriate QC tool for analysis of ALG in tablets.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 1106-1112
Author(s):  
Ibrahim A. Darwish ◽  
Nasr Y. Khalil ◽  
Mohammad AlZeer
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Internal Standard ◽  
Dosage Forms ◽  
Uv Detector ◽  
Stability Indicating ◽  
Therapeutic Benefits ◽  
Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

scholarly journals Charged aerosol detector response modeling for fatty acids based on experimental settings and molecular features: a machine learning approach

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruben Pawellek ◽  
Jovana Krmar ◽  
Adrian Leistner ◽  
Nevena Djajić ◽  
Biljana Otašević ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mobile Phase ◽  
Molecular Descriptors ◽  
Attribute Selection ◽  
Selection Strategy ◽  
Detector Response ◽  
Experimental Conditions ◽  
Molecular Features ◽  
Charged Aerosol ◽  
Charged Aerosol Detector

AbstractThe charged aerosol detector (CAD) is the latest representative of aerosol-based detectors that generate a response independent of the analytes’ chemical structure. This study was aimed at accurately predicting the CAD response of homologous fatty acids under varying experimental conditions. Fatty acids from C12 to C18 were used as model substances due to semivolatile characterics that caused non-uniform CAD behaviour. Considering both experimental conditions and molecular descriptors, a mixed quantitative structure–property relationship (QSPR) modeling was performed using Gradient Boosted Trees (GBT). The ensemble of 10 decisions trees (learning rate set at 0.55, the maximal depth set at 5, and the sample rate set at 1.0) was able to explain approximately 99% (Q2: 0.987, RMSE: 0.051) of the observed variance in CAD responses. Validation using an external test compound confirmed the high predictive ability of the model established (R2: 0.990, RMSEP: 0.050). With respect to the intrinsic attribute selection strategy, GBT used almost all independent variables during model building. Finally, it attributed the highest importance to the power function value, the flow rate of the mobile phase, evaporation temperature, the content of the organic solvent in the mobile phase and the molecular descriptors such as molecular weight (MW), Radial Distribution Function—080/weighted by mass (RDF080m) and average coefficient of the last eigenvector from distance/detour matrix (Ve2_D/Dt). The identification of the factors most relevant to the CAD responsiveness has contributed to a better understanding of the underlying mechanisms of signal generation. An increased CAD response that was obtained for acetone as organic modifier demonstrated its potential to replace the more expensive and environmentally harmful acetonitrile.

scholarly journals LC-MS characterization of acid degradation products of metoclopramide: Development and validation of a stability-indicating RP-HPLC method

2020 ◽  
Vol 11 (1) ◽  
pp. 781-789
Author(s):  
Sriram Valavala ◽  
Nareshvarma Seelam ◽  
Subbaiah Tondepu ◽  
Suresh Kandagatla
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Limit Of Quantification ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Hplc Technique

The present study aims to develop a simple, accurate and specific stability-indicating RP-HPLC technique for the analysis of metoclopramide in the presence of its stress degradation products and characterization of degradation compounds by LC-MS/MS analysis. As per ICH Q1A-R2 guidelines, the drug was exposed to acid hydrolytic stress condition. Three degradation products were formed for MCP in acid hydrolysis. The liquid chromatography was processed on a Luna C18-(2) 100A,250×4.6mm 5micron column using an isocratic mobile phase consisting of 0.1% formic acid in water-acetonitrile (20:80, v/v) by adjusting the mobile phase at 1 ml/min flow rate with wavelength detection at 273 nm. The developed procedure was applied to LC-MS/MS (liquid chromatography-tandem mass spectrometry) for the characterization of all the degradant components. Total new three degradation compounds were recognized and identified by LC-MS/MS. The developed RP-HPLC technique was validated as per the ICH Q2-R1 guidelines. Limit of detection and limit of quantification values of MCP were evaluated from the linearity graph and were found to be 5.23 µg/ml and 17.44 µg/ml. Accuracy study was established at 80.0, 100.0 and 120.0 µg/ml concentration levels and the findings were found in the range of 98.4% - 101.8%. The linearity of the technique was assessed over the drug concentration range of 50.0 µg/ml to 250.0 µg/ml and the regression equation, slope and correlation coefficient values were found to be y = 10618x + 1623.2, 10618 and 0.9996 respectively. The developed technique was uninterruptedly applied for the quantification of metoclopramide inactive pharmaceuticals.

scholarly journals High-performance liquid chromatography of uroporphyrinogen and coproporphyrinogen isomers with amperometric detection

1986 ◽  
Vol 234 (3) ◽  
pp. 629-633 ◽  
Author(s):  
C K Lim ◽  
F Li ◽  
T J Peters
Keyword(s):  
Mobile Phase ◽  
High Performance ◽  
Ammonium Acetate ◽  
Amperometric Detection ◽  
Reversed Phase ◽  
Fluorescent Detection ◽  
Organic Modifiers ◽  
Ammonium Acetate Buffer ◽  
Effects Of Ph ◽  
Ph Buffer

A reversed-phase h.p.l.c. system, with an ODS-Hypersil column with acetonitrile or methanol in ammonium acetate buffer as mobile phase, is described for the separation of uro-and copro-porphyrinogen isomers. The porphyrinogens are detected amperometrically with sensitivity comparable with that of the fluorescent detection of porphyrins. The effects of pH, buffer concentration and organic modifiers on retention and resolution were studied. The method is suitable for both analytical and preparative separation of porphyrinogens.

scholarly journals Development and Validation of a Novel Stability-Indicating Reversed-Phase Ion-Pair Chromatographic Method for the Quantitation of Impurities in Marbofloxacin Tablets

2018 ◽  
Vol 101 (4) ◽  
pp. 1021-1029
Author(s):  
Priyanka Maheshwari ◽  
Neelima Shukla ◽  
Manish Kumar Dare
Keyword(s):  
Mobile Phase ◽  
Chromatographic Method ◽  
Degradation Products ◽  
Reversed Phase ◽  
Ion Pair ◽  
Stress Conditions ◽  
Main Peak ◽  
Stability Indicating ◽  
Photolytic Degradation ◽  
The Stability

Abstract A stability-indicating isocratic reversed-phase ion-pair chromatographic method was designed for the separation of impurities in the presence of degradation products. Marbofloxacin tablets and a placebo were exposed to the stress conditions of oxidative, acid, base, humidity, thermal, and photolytic degradation. Significant and moderate degradation was observed in acidic and oxidative stress conditions, respectively. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating analytical method. The method was developed by using an XTerra RP18 3.5 μm (150 × 4.6 mm) column, with the mobile phase containing a mixture of buffer (pH 2.5)–methanol–glacial acetic acid (77 + 23 + 0.5, v/v). The flow rate of the mobile phase was 1.2 mL/min, with a column oven temperature of 40°C and a detection wavelength of 315 nm. The proposed method met Veterinary International Conference on Harmonization requirements and was successfully used for impurity quantitation in marbofloxacin tablets.

Stability-Indicating Liquid Chromatographic Procedure for Determination of Allantoin in Cosmetic Lotion

1988 ◽  
Vol 71 (2) ◽  
pp. 290-294
Author(s):  
Ramesh J Trivedi
Keyword(s):  
Degradation Products ◽  
Glyoxylic Acid ◽  
Uv Detector ◽  
Stability Indicating ◽  
Assay Procedure ◽  
Relative Standard ◽  
The Stability ◽  
Chromatographic Parameters ◽  
Liquid Chromatographic

Abstract A sensitive, specific liquid chromatographic (LC) procedure was developed for determination of allantoin [(2,5-dioxo-4--imidaazolidinyl) urea or 5-ureidohydantion] in cosmetic lotion. A reverse-phase, ionsuppression mechanism separated allantoin from interfering constituents of the sample matrix, and the compound was determined with a UV detector at 240 nm with a sensitivity limit of ((.20 mg/mL. The chromatographic parameters were optimized for retention time, efficiency, and relative response to the analyte. The assay procedure was validated with spiked laboratory-prepared samples at 100 ± 15% levels. An average recovery of 99.4% with a relative standard deviation of 1.5% (n = 7) was obtained. The stability-indicating characteristics of the method were established by recovery study (99.8%) of samples spiked with known degradation products (urea, allantoic acid, and glyoxylic acid).

scholarly journals Stability-Indicating Validated HPLC Method for Simultaneous Determination of Oral Antidiabetic Drugs from Thiazolidinedione and Sulfonylurea Groups in Combined Dosage Forms

2010 ◽  
Vol 93 (4) ◽  
pp. 1086-1092 ◽  
Author(s):  
Anna Gumieniczek ◽  
Anna Berecka ◽  
ukasz Komsta
Keyword(s):  
Simultaneous Determination ◽  
Mobile Phase ◽  
Uv Light ◽  
Degradation Products ◽  
Dosage Forms ◽  
Hplc Method ◽  
Base Temperature ◽  
Stability Indicating ◽  
Acid And Base

Abstract For type 2 diabetes treatment, combinations of drugs from the thiazolidinedione and sulfonylurea groups are now available in the same tablet or capsule. Therefore, a stability-indicating and validated HPLC method was developed for simultaneous determination of pioglitazone, rosiglitazone, and glipizide in combined dosage forms. The examined drugs were subjected to different conditions such as acid and base, temperature, and UV light, and degradation of pioglitazone and glipizide was observed under thermal and acidic stress. However, selectivity of the presented method for pioglitazone, rosiglitazone, and glipizide assay against their degradation products was confirmed. It was also demonstrated to be robust, resisting small deliberate changes in pH of the buffer, flow rate, and percentage of acetonitrile in the mobile phase. The presented method utilizes a LiChrospher RP18 column (125 4.0 mm), acetonitrile in phosphate buffer at pH 4.3 (40 + 60, v/v) as the mobile phase, and UV detection at 225 nm for pioglitazone/glipizide or 245 nm for rosiglitazone/glipizide. The method was validated with respect to linearity, precision, and accuracy. Finally, the elaborated procedure was applied for the QC of pioglitazone/glipizide and rosiglitazone/glipizide mixtures.

scholarly journals DEVELOPMENT AND VALIDATION OF STABILITY-INDICATING REVERSE-PHASE HIGHPERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE SIMULTANEOUS QUANTIFICATION OF POTENTIAL DEGRADATION PRODUCTS OF REGADENOSON FROM ITS PARENTERAL DOSAGE FORM

2018 ◽  
Vol 11 (8) ◽  
pp. 277
Author(s):  
Murlidhar V Zope ◽  
Rahul M Patel ◽  
Ashwinikumari Patel ◽  
Samir G Patel
Keyword(s):  
Liquid Chromatography ◽  
Degradation Product ◽  
Mobile Phase ◽  
Dosage Form ◽  
Degradation Products ◽  
Reverse Phase ◽  
Chromatography Method ◽  
Stability Indicating ◽  
Liquid Chromatography Method ◽  
Injectable Dosage

Objective: The objective was to develop and validate the stability indicating reverse-phase high-performance liquid chromatography method for the quantification of potential degradation products of regadenoson (REGA) from its injectable dosage form.Methods: YMC-PAK ODS AQ, 150 mm × 4.6 mm, 3 μm composed with hydrophobic high carbon loading and a relatively hydrophilic surface chemically bonded to porous silica particles column was used with the temperature maintained at 40°C. Mobile phase A composed of 0.1% triethylamine buffer having pH 4.5 while mobile phase B is 100 % acetonitrile was used for gradient elution with 1.5 ml/min as a flow rate. The wavelength used for quantification was 245 nm and 20 μl as an injection volume. The suitability of the method has been checked and validated according to the International Council for Harmonization (ICH) guidelines for different parameters, namely, specificity, linearity, accuracy, precision, limit of quantification (LOQ), Limit of detection (LOQ), and robustness studies.Results: The resolution between REGA and its two-degradation product is >8.0 for all pairs of components. The high correlation coefficient (r2>0.990) values are for drug and all potential degradation products from LOQ to 150% of specification limits for impurities calculated based on the maximum daily dose of REGA. LOQ for the drug as well as each degradation product is <0.02% w/w. The % relative standard deviation (RSD) for precision and intermediate precision is in the range of 0.17–0.89, and % RSD for precision at LOQ is 0.86–2.35. The % RSD for robustness study is maximum 2.59.Conclusion: The developed method can quantify the specified and unknown degradation products from 0.1% in the injectable dosage form which indicates that method is sensitive. Method fulfills the ICH criteria for its different validation parameters and demonstrates that the developed analytical method is highly specific, precise, and robust and would have a great value when applied in quality control and stability studies for REGA injection.

Stability-Indicating Methods for the Determination of Candesartan Cilexetil in Bulk Drug and Pharmaceutical Formulations

2013 ◽  
Vol 96 (3) ◽  
pp. 580-586 ◽  
Author(s):  
Yousry M Issa ◽  
Emad M Hussien ◽  
Magda M Ibrahim ◽  
Fatma M Abdel-Gawad ◽  
Saadia Barakat
Keyword(s):  
Mobile Phase ◽  
Candesartan Cilexetil ◽  
Degradation Products ◽  
Pharmaceutical Formulations ◽  
Stability Indicating ◽  
Bulk Powder ◽  
System Suitability ◽  
The Mean ◽  
Bulk Drug

Abstract Two stability-indicating methods were developed for the determination of candesartan cilexetil in the presence of its degradation products. The first method uses isocratic RP-HPLC with an Agilent C18 column. The mobile phase was phosphate buffer (pH = 2.8 ± 0.1)–acetonitrile (60 + 40, v/v). The flow rate was 2.0 mL/min, and the UV detection was at 254 nm. The second method depends on TLC-densitometric measurements of drug spots at 254 nm. The separation was carried out on silica gel 60 F254 plates using ethyl acetate–methanol–toluene– ammonia 33% (40 + 25 + 20 + 2, v/v/v/v) mobile phase. The methods were validated according to U.S. Pharmacopeia guidelines, and the acceptance criteria for accuracy, precision, linearity, specificity, robustness, LOD, LOQ, and system suitability were met in all cases. Linear ranges of the methods were 10.0–200.0 μg/mL and 1.0–9.0 μg/spot for HPLC and TLC, respectively. The proposed methods were successfully applied to the drug in bulk powder, in laboratory-prepared mixtures with its degradation products, and in commercially available tablets. The results were compared statistically at the 95% confidence level with each other. There were no significant differences between the mean recovery and precision of the two methods.

scholarly journals STABILITY-INDICATING METHOD FOR DETERMINATION OF TIZANIDINE HYDROCHLORIDE IN PHARMACEUTICAL LC-CAD METHOD USING CHEMOMETRIC APPROACH

2017 ◽  
Vol 1 (1) ◽  
pp. 61-66
Author(s):  
Mariana Brandalise ◽  
Pamela Cristina Lukasewicz Ferreira ◽  
Andrea Garcia Pereira ◽  
Leonardo Meneghini ◽  
Pedro Eduardo Fröehlich ◽  
...  
Keyword(s):  
Ammonium Acetate ◽  
Forced Degradation ◽  
Simple Method ◽  
Stability Indicating Method ◽  
Charged Aerosol ◽  
Charged Aerosol Detector ◽  
Chemometric Approach ◽  
Tablet Dosage ◽  
Drug Reference

A new LC method for tizanidine hydrochloride in tablet dosage form using a charged aerosol detector (CAD) is described. The influence of various parameters on chromatographic system was investigated by factorial designs and Derringer's desirability. Chromatographic conditions were: mobile phase constituted of acetonitrile and ammonium acetate buffer 17 mM (60:40; v/v), column oven at 39 °C and flow rate 0.8 mL.min-1 performed in on Acclaim Trinity P1 column UV at 230 nm. Thus, it was possible to validate a simple method to assay the tizanidine and its counter-ion in three formulations (drug reference, generic and manipulated). Method showed specificity when challenged by forced degradation and excipients. Finally, the method was compared with USP monograph method demonstrating equivalence in assay evaluation.

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