Development and Validation of a Stability-Indicating HPLC-Photodiode Array Detector Method for Formulation Analysis and Degradation Kinetics and Dissolution Studies of Mycophenolate Sodium and HPLC/MS/MS Characterization of its Stress Degradation Products

2013 ◽  
Vol 96 (3) ◽  
pp. 593-598
Author(s):  
Anna Pratima G Nikalje ◽  
Vishnu P Choudhari
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Degradation Kinetics ◽  
Array Detector ◽  
Forced Degradation ◽  
Product Analysis ◽  
Mycophenolate Sodium ◽  
Stability Indicating ◽  
Stress Degradation

Abstract A simple stability-indicating isocratic RP-HPLC method was developed and validated for the determination of mycophenolate sodium and its alkali degradation product. Forced degradation of the drug was carried out under thermolytic, photolytic, acid/base hydrolytic, and oxidative stress conditions. Alkali degradation product DP1 was isolated, and separation of stress degradation products was achieved on a Symmetry C18 (250 × 4.6 mm × 5.0 μm) column using the mobile phase methanol–acetate buffer adjusted with acetic acid to pH 6.0 (76 + 24, v/v) at a 0.55 mL/min flow rate and 50°C. Data were integrated at the detection wavelength of 251 nm. The method validation characteristics included accuracy, precision, linearity, range, specificity, and sensitivity per International Conference on Harmonization guidelines. Robustness testing was conducted to evaluate the effect of minor changes in the chromatographic conditions and to establish appropriate system suitability parameters. Structural elucidation of degraded products was performed by HPLC/MS/MS. The method was used successfully for drug product analysis, dissolution study, and determination of the drug's acid, alkali, and oxidative degradation kinetics.

scholarly journals DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR DETERMINATION OF β-ACETYLDIGOXIN

2016 ◽  
Vol 9 (1) ◽  
pp. 54
Author(s):  
Megha Sharma ◽  
Neeraj Mahindroo
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Hplc Method ◽  
Stability Study ◽  
Array Detector ◽  
Forced Degradation ◽  
Simple Method ◽  
Stability Indicating ◽  
Rp Hplc

Objective: The objective of the present study was to develop and validate a novel stability indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for determination of β-acetyldigoxin, an active pharmaceutical ingredient (API).Methods: The chromatographic separation was carried out on Agilent Technologies 1200 series HPLC system equipped with photo diode array detector and C-18 (4.6x250 mm, 5 µ) column. The mobile phase consisted of water: acetonitrile (65:35 v/v), delivered at a flow rate of 1.5 ml/min and eluents were monitored at 225 nm.Results: The retention time of β-acetyldigoxin was 9.2 min. The method was found to be linear (R2= 0.9995) in the range of 31.25-500 µg/ml. The accuracy studies showed the mean percent recovery of 101.02%. LOD and LOQ were observed to be 0.289 µg/ml and 0.965 µg/ml, respectively. The method was found to be robust and system suitability testing was also performed. Forced degradation analysis was carried out under acidic, alkaline, oxidative and photolytic stress conditions. Significant degradation was observed under tested conditions, except for oxidative condition. The method was able to separate all the degradation products within runtime of 20 min and was able to determine β-acetyldigoxin unequivocally in presence of degradation products.Conclusion: The novel, economic, rapid and simple method for analysis of β-acetyldigoxin is reported. The developed method is suitable for routine quality control and its determination as API, and in pharmaceutical formulations and stability study samples.

Validated Stability-Indicating Capillary Electrophoresis Method for the Separation and Determination of a Fixed-Dose Combination of Carvedilol and Hydrochlorothiazide in Tablets

2013 ◽  
Vol 96 (5) ◽  
pp. 951-959 ◽  
Author(s):  
Nourah Z Alzoman ◽  
Maha A Sultan ◽  
Hadir M Maher ◽  
Mona M AlShehri ◽  
Ileana V Olah
Keyword(s):  
Capillary Electrophoresis ◽  
Degradation Products ◽  
Background Electrolyte ◽  
Internal Standard ◽  
Fused Silica ◽  
Fixed Dose ◽  
Array Detector ◽  
Forced Degradation ◽  
Stability Indicating

Abstract A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diode array detector has been developed for the separation and simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in two combination formulations. The proposed method utilized a fused silica capillary (55 cm × 75 μm id) and the background electrolyte solution phosphate buffer (12.5 mM, pH 7.4)–methanol (95 + 5, v/v). The separation was achieved at 30 kV applied voltage and 24°C. Atorvastatin (80 μg/mL) was chosen as the internal standard. The described method was linear over the range of 1–200 and 0.2–150 μg/mL for CRV and HCT, respectively. Intraday and interday RSD (n = 6) was ≤1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 μg/mL, respectively. The validated CE method was successfully applied to the analysis of two commercial tablet dosage forms. Forced degradation studies were performed on bulk samples of the two drugs using thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation products produced as a result of stress studies did not interfere with the determination of CRV and HCT; the assay could, therefore, be considered stability-indicating.

scholarly journals A Stability-Indicating HPLC-DAD Method for Determination of Ferulic Acid into Microparticles: Development, Validation, Forced Degradation, and Encapsulation Efficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jessica Mendes Nadal ◽  
Maria da Graça Toledo ◽  
Yasmine Mendes Pupo ◽  
Josiane Padilha de Paula ◽  
Paulo Vitor Farago ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Degradation Kinetics ◽  
Forced Degradation ◽  
Detection Accuracy ◽  
Stability Indicating ◽  
Relative Standard ◽  
Polymeric Microparticles

A simple stability-indicating HPLC-DAD method was validated for the determination of ferulic acid (FA) in polymeric microparticles. Chromatographic conditions consisted of a RP C18column (250 mm × 4.60 mm, 5 μm, 110 Å) using a mixture of methanol and water pH 3.0 (48 : 52 v/v) as mobile phase at a flow rate of 1.0 mL/min with UV detection at 320 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of quantification, limit of detection, accuracy, precision, and robustness provided suitable results regarding all parameters investigated. The calibration curve was linear in the concentration range of 10.0–70.0 μg/mL with a correlation coefficient >0.999. Precision (intraday and interday) was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of FA from polymeric microparticles (99.02% to 100.73%). Specificity showed no interference from the components of polymeric microparticles or from the degradation products derived from acidic, basic, and photolytic conditions. In conclusion, the method is suitable to be applied to assay FA as bulk drug and into polymeric microparticles and can be used for studying its stability and degradation kinetics.

scholarly journals DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF POTENTIAL DEGRADATION PRODUCTS OF DIFLUPREDNATE IN OPHTHALMIC EMULSION

2018 ◽  
Vol 10 (9) ◽  
pp. 79 ◽  
Author(s):  
Murlidhar V. Zope ◽  
Rahul M. Patel ◽  
Ashwinikumari Patel ◽  
Samir G. Patel
Keyword(s):  
Quantitative Determination ◽  
Degradation Product ◽  
Mobile Phase ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Rp Hplc

Objective: The objective of the current study was to develop and validate a simple, robust, precise and accurate RP-HPLC (reverse phase-high performance liquid chromatography) method for the quantitative determination of potential degradation products of Difluprednate (DIFL) in the ophthalmic emulsion.Methods: Chromatographic separation was achieved on the YMC pack ODS-AQ (150× 4.6) mm, 3μm column with a mobile phase containing a gradient mixture of mobile phase A (0.02M Ammonium formate buffer pH 4.5 adjusted with formic acid) and Acetonitrile as mobile phase B, at flow rate of 1.5 ml/min and with UV detection at 240 nm.Results: The peak retention time of DIFL was found at about 17.2 min, the RRT of degradation product-1 (DP-1), degradation product-2 (DP-2), and degradation product-3 (DP-3), were found to be about 0.49, 0.65 and 0.79 respectively (calculated with respect to Difluprednate). Stress testing was performed in accordance with an ICH (international council for harmonisation) guideline Q1A (R2) [1]. The method was validated as per ICH guideline Q2 (R1)[2]. The calibration curve was found to be linear in the concentration range of 0.1 to 0.75 µg/ml for Difluprednate, DP-1, DP-2 and DP-3. The LOD (Limit of detection) was found to be 0.1µg/ml and LOQ (Limit of quantification) of 0.15µg/ml for Difluprednate, DP-1, DP-2 and DP-3 respectively. The recovery from LOQ to 150% was within 90-110%. The forced degradation data confirms the stability indicating the nature of the method.Conclusion: A simple, robust, precise and accurate RP-HPLC method for the quantitative determination of potential degradation products of Difluprednate in the ophthalmic emulsion was developed and validated. 

scholarly journals Development of a Stability Indicating Method for Simultaneous Analysis of Five Water-Soluble Vitamins by Liquid Chromatography

2018 ◽  
Vol 3 (4) ◽  
pp. 207-218 ◽  
Author(s):  
Mouloud Yessaad ◽  
Lise Bernard ◽  
Daniel Bourdeaux ◽  
Philip Chennell ◽  
Valérie Sautou
Keyword(s):  
Liquid Chromatography ◽  
Degradation Products ◽  
Pharmaceutical Preparations ◽  
Water Soluble ◽  
Alkaline Solutions ◽  
Array Detector ◽  
Forced Degradation ◽  
Metaphosphoric Acid ◽  
Stability Indicating ◽  
Stability Indicating Method

Abstract Background Water-soluble vitamins are often included simultaneously in pharmaceutical formulations as food complements or in parenteral nutrition mixtures. Given their sensitivity to heat, light or pH variations, it is important to study their stability using validated stability indicating methods. We thus aimed to validate a liquid chromatography (LC) stability-indicating method for the simultaneous quantification of 5 water-soluble vitamins. Methods We analyzed four water-soluble B vitamins (nicotinamide, pyridoxine, folic acid, cyanocobalamin) and ascorbic acid using a LC method with diode array detector. They were separated on a C18 stationary phase under gradient elution of solvent A [0.2 % of metaphosphoric acid in water and acetonitrile 98:2] and solvent B (100 % acetonitrile). All vitamins were subjected to forced degradation conditions and we showed that the obtained degradation products didn’t interfere with the vitamins. Results The method allows the separation of the 5 water-soluble vitamins in a 30 minute run without any interference from the breakdown products obtained with acid/alkaline solutions, hydrogen peroxide, temperature and light. It meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity. Conclusions This stability-indicating method can be used for carrying out stability studies of water-soluble vitamins in pharmaceutical preparations.

scholarly journals STABILITY INDICATING HPLC METHOD FOR DETERMINATION OF VILAZODONE HYDROCHLORIDE

2017 ◽  
Vol 9 (4) ◽  
pp. 123
Author(s):  
Birva A. Athavia ◽  
Zarna R. Dedania ◽  
Ronak R. Dedania ◽  
S. M. Vijayendra Swamy ◽  
Chetana B. Prajapati
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Alkaline Condition ◽  
Forced Degradation ◽  
Molecular Formula ◽  
Stability Indicating ◽  
Dry Heat ◽  
Limit Of Quantitation

Objective: The aim and objective of this study was to develop and validate Stability Indicating HPLC method for determination of Vilazodone Hydrochloride.Methods: The method was carried out on a Phenomenex, C18 (250x4.6 mm, 5 µm) Column using a mixture of Acetonitrile: Water (50:50v/v), pH adjusted to 3.3 with Glacial Acetic Acid for separation. The flow rate was adjusted at 1 ml/min and Detection was carried out at 240 nm.Results: The retention time of vilazodone hydrochloride was found to be 2.3 min. The calibration curve was found to be linear in the range 25-75µg/ml with a correlation coefficient (R2=0.996). The limit of detection and limit of quantitation were found to be 4.78µg/ml and 14.48µg/ml respectively. The % recovery of vilazodone hydrochloride was found to be in the range of 98.21±0.08 % to 99.07±0.64%. The proposed method was successfully applied for the estimation of vilazodone hydrochloride in marketed tablet formulation.Vilazodone Hydrochloride was subjected to forced degradation under Acidic, Alkaline, Oxidation, Dry Heat and Photolytic degradation conditions. Vilazodone hydrochloride showed 3.12% degradation under acidic condition, 4.78% under alkaline condition, 7.8% under oxidation condition, 3.53% under dry heat condition and 4.9% under photolytic condition.Acid degradation impurity was identified and characterised by LC-MS/MS was found to be 1-(4-Penten-1-yl) piperazine having molecular weight 154.253 (m/z 155.08) and Molecular Formula C9H18N2.Conclusion: A simple, precise, rapid and accurate Stability Indicating HPLC method has been developed and validated for the determination of Vilazodone Hydrochloride in presence of its degradation products as per the ICH Guidelines. 

Eco-Friendly Green Liquid Chromatographic Determination of Azelastine in the Presence of its Degradation Products: Applications to Degradation Kinetics

2019 ◽  
Vol 102 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Amal A El-Masry ◽  
Mohammed E A Hammouda ◽  
Dalia R El-Wasseef ◽  
Saadia M El-Ashry
Keyword(s):  
Degradation Products ◽  
Degradation Kinetics ◽  
Sodium Dodecyl ◽  
Internal Standard ◽  
Eye Drops ◽  
Control Analysis ◽  
Stability Indicating ◽  
Highly Sensitive ◽  
Antihistaminic Drug

Abstract Background: Green solvents such as microemulsion were used in the proposed method because they play a vital role in the analytical method’s influence on the environment. Objective: A highly sensitive, specific, and validated stability-indicating eco-friendly green microemulsion liquid chromatography (MELC) method was developed for separation of the antihistaminic drug Azelastine HCl (AZL) from its degradation products with application to degradation kinetics. Methods: Chromatographic separation was operated on a C18 column with a microemulsion mobile phase, which consists of 0.1 M sodium dodecyl sulphate, 10% n-propanol, 1% n-octanol, and 0.3% triethylamine, by using 0.02 M phosphoric acid at pH 3.5 and irbesartan as internal standard. The eluted compounds were monitored at 210 nm with flow rate 1 mL/min at ambient temperature. Results: A linear dependence of the peak area on drug concentration over the concentration range of 0.1 to 25 μg/mL was achieved with an LOD of 0.04 μg/mL and an LOQ of 0.10 μg/mL. Moreover, the proposed method was successfully applied for determination of AZL in eye drops and metered dose nasal inhaler as well as to study the kinetics of alkaline, acidic, neutral, oxidative, and photolytic degradation processes of AZL according to the International Council for Harmonization guidelines. Conclusions: The proposed method could be used as a harmless alternative for quality control analysis of the mentioned drug, without interference from dosage form additives or decomposition products. Highlights: A highly sensitive stability-indicating eco-friendly green MELC method was developed for the separation of the antihistaminic drug AZL from its degradation products.

scholarly journals Determination of Rosuvastatin in the Presence of Its Degradation Products by a Stability-Indicating LC Method

2005 ◽  
Vol 88 (4) ◽  
pp. 1142-1147 ◽  
Author(s):  
Tushar N Mehta ◽  
Atul K Patel ◽  
Gopal M Kulkarni ◽  
Gunta Suubbaiah
Keyword(s):  
Degradation Products ◽  
Stability Study ◽  
Tablet Formulation ◽  
Assay Method ◽  
Forced Degradation ◽  
Degradation Study ◽  
Stability Indicating ◽  
Degraded Samples ◽  
Accelerated Stability

Abstract A forced degradation study was successfully applied for the development of a stability-indicating assay method for determination of rosuvastatin Ca in the presence of its degradation products. The method was developed and optimized by analyzing the forcefully degraded samples. Degradation of the drug was done at various pH values. Moreover, the drug was degraded under oxidative, photolytic, and thermal stress conditions. Mass balance between assay values of degraded samples and generated impurities was found to be satisfactory. The proposed method was able to resolve all of the possible degradation products formed during the stress study. The developed method was successfully applied for an accelerated stability study of the tablet formulation. The major impurities generated during the accelerated stability study of the tablet formulation were matches with those of the forced degradation study. The developed method was validated for determination of rosuvastatin Ca, and the method was found to be equally applicable to study the impurities formed during routine and forced degradation of rosuvastatin Ca.

Stability-indicating LC method for the determination of cephalothin in lyophilized powder for injection

2014 ◽  
Vol 6 (12) ◽  
pp. 4437-4445 ◽  
Author(s):  
Karen de Souza Rugani ◽  
Hérida Regina Nunes Salgado
Keyword(s):  
Liquid Chromatography ◽  
Degradation Products ◽  
Reversed Phase ◽  
Forced Degradation ◽  
Antimicrobial Compound ◽  
Reversed Phase Liquid Chromatography ◽  
Stability Indicating ◽  
Forced Degradation Studies ◽  
Phase Liquid

A stability-indicating gradient reversed phase liquid chromatography (RP-LC) method has been developed for the quantitative determination of cephalothin (CET), an antimicrobial compound, in the presence of its impurities and degradation products generated from forced degradation studies.

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