Investigation of ethosuximide stability under certain ICH-recommended stress conditions using a validated stability-indicating HPLC method

2018 ◽  
Vol 10 (12) ◽  
pp. 1452-1458
Author(s):  
Y. El-Shabrawy ◽  
M. Walash ◽  
N. El-Enany ◽  
R. El-Shaheny
Keyword(s):  
Chemical Stability ◽  
Hplc Method ◽  
Stress Conditions ◽  
Stability Indicating

An HPLC investigation of the chemical stability of ethosuximide was conducted under certain ICH-recommended stress conditions.

scholarly journals Development and Validation of a Stability-Indicating RP-HPLC Method for Determination of Atomoxetine Hydrochloride in Tablets

2010 ◽  
Vol 93 (4) ◽  
pp. 1207-1214 ◽  
Author(s):  
Sejal K Patel ◽  
Natvarlal J Patel
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Stress Conditions ◽  
Acid Base ◽  
Photodiode Array Detection ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Rp Hplc ◽  
Wet Heat

Abstract This paper describes the development of a stability-indicating RP-HPLC method for the determination of atomoxetine hydrochloride (ATX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. In stability tests, the drug was susceptible to acid, base, oxidation, and dry and wet heat degradation. It was found to be stable under the photolytic conditions tested. The drug was successfully separated from the degradation products formed under stress conditions on a Phenomenex C18 column (250 4.6 mm id, 5 m particle size) by using acetonitrilemethanol0.032 M ammonium acetate (55 + 05 + 40, v/v/v) as the mobile phase at 1.0 mL/min and 40C. Photodiode array detection at 275 nm was used for quantitation after RP-HPLC over the concentration range of 0.55 g/mL with a mean recovery of 100.8 0.4 for ATX. Statistical analysis demonstrated that the method is repeatable, specific, and accurate for the estimation of ATX. Because the method effectively separates the drug from its degradation products, it can be used as a stability-indicating method.

scholarly journals Stability-Indicating RP-HPLC Method Development and Validation for Duloxetine Hydrochloride in Tablets

2010 ◽  
Vol 93 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Sejal K Patel ◽  
Natavarlal J Patel ◽  
Arun M Prajapati ◽  
Dipti B Patel ◽  
Satish A Patel
Keyword(s):  
Method Development ◽  
Degradation Products ◽  
Hplc Method ◽  
Stress Conditions ◽  
Photodiode Array Detection ◽  
Heat Condition ◽  
Stability Indicating ◽  
Dry Heat ◽  
Duloxetine Hydrochloride ◽  
Rp Hplc

Abstract This paper describes the development of a stability-indicating RP-HPLC method for duloxetine hydrochloride (DLX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was found to be susceptible to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. The drug was found to be stable to the dry heat condition attempted. Successful separation of the drug from the degradation products formed under stress conditions was achieved on a Phenomenex C18 column (250 4.6 mm id, 5 µm particle size) using acetonitrilemethanol0.032 M ammonium acetate buffer (55 + 05 + 40, v/v/v) as the mobile phase at a flow rate of 1.0 mL/min at 40°C temperature. Quantification was achieved with photodiode array detection at 290 nm over the concentration range 0.25 µg/mL with mean recovery of 101.048 ± 0.53 for DLX by the RP-HPLC method. Statistical analysis proved the method is repeatable, specific, and accurate for estimation of DLX. Because the method could effectively separate the drug from its degradation products, it can be used as a stability-indicating method.

scholarly journals A VALIDATED STABILITY INDICATING RP-HPLC METHOD FOR ESTIMATION OF TOLFENAMIC ACID IN PRESENCE OF ITS PHARMACOPOEIAL IMPURITIES

2019 ◽  
pp. 264-270
Author(s):  
ADISON FERNANDES ◽  
SANJAY PAI P. N.
Keyword(s):  
Oxidative Stress ◽  
Correlation Coefficient ◽  
Flow Rate ◽  
Hplc Method ◽  
Tolfenamic Acid ◽  
Stress Conditions ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Related Impurities ◽  
Rp Hplc

Objective: The proposed research work was conducted to develop a single reverse-phase high-performance chromatography (RP-HPLC) method capable of separating two Pharmacopoeial related impurities as well as degradation product of Tolfenamic acid (TA). The drug was subjected to various stress conditions recommended under ICH Q1A (R2) guidelines. Methods: The desired separation of two Pharmacopoeial impurities and one degradant generated under oxidative stress was carried out using Sunfire ODS C-18 (250 x 4.6 mm, 5 µm) column maintained at 40 °C. Isocratic elution was carried out using acetonitrile and ammonium dihydrogen orthophosphate buffer (10 mmol, pH 2.5) in the ratio of 80:20 v/v. The detection was carried out at 205 nm using flow rate of 1 ml/min. The developed method was validated as per ICH Q2 (R1) guidelines for specificity, linearity, accuracy, precision, Limit of detection (LOD), Limit of Quantification (LOQ) and robustness. Results: Linearity response of TA was found at a concentration range of 10-100µg/ml, with a correlation coefficient of 0.9987. The Pharmacopoeial impurity A and impurity B showed linearity results at concentration of 0.1-1µg/ml, with correlation coefficient of 0.9984 for Impurity A and 0.9989 for Impurity B. The % recovery during accuracy studies for TA and the two impurities were within the acceptance range of 95-105%. LOD and LOQ for TA were found to be 4.561µg/ml and 133.771µg/ml respectively. For impurity A, LOD and LOQ were found to be 0.035 µg/ml and 0.106 µg/ml and for Impurity B, LOD and LOQ were 0.042 µg/ml and 0.128 µg/ml. With slight variation of organic phase in mobile phase and flow rate the method exhibited good robustness. Under forced degradation studies the drug was found stable under hydrolytic, photolytic and thermal stress conditions, but was found susceptible for degradation under oxidative stress with appearance of a degradant peak. From on the RRT values of Pharmacopoeial impurities and the formed degradant it was inferred that the developed method is selective for the drug in the presence of impurities or degradants. Conclusion: The developed stability-indicating method is found to be simple, rapid, accurate, precise and robust as compared to other proposed methods while determining TA in presence of its Pharmacopoeial impurities and degradation products. Hence the developed method can be used for analysis of stability samples of TA in presence of its related impurities.

A new stability indicating chiral RP-HPLC method for determination of degradation products in Meclizine Hydrochloride

2020 ◽  
Vol 16 ◽  
Author(s):  
Bryan Gowramma ◽  
Ramachandran Senthil Kumar ◽  
Kaviarasan Lakshmanan ◽  
Rajagopal Kalirajan ◽  
Subramanian Nainar Meyyanathan
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Pharmaceutical Preparations ◽  
Hplc Method ◽  
Stress Conditions ◽  
Main Peak ◽  
Uv Detector ◽  
Limit Of Quantification ◽  
Degradation Behaviour ◽  
Stability Indicating

Background: An enantiomeric separation of stability-indicating high-performance liquid chromatographic method was developed and validated for the analysis of Meclizine enantiomers. The degradation behaviour of Meclizine Hydrochloride was investigated under different stress conditions recommended by International Conference on Harmonization (ICH). Experiment: Enantiomeric resolution of the drug and complete separation from its degradation products were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 µm particle size) column, using UV detector at a wavelength of 230 nm, with mobile phase consisting of acetonitrile, 20mM ammonium bicarbonate at the ratio of 75:25 (v/v), and a flow rate of 1 mL/min. The drug was subjected to alkaline, acidic, neutral, oxidative and photolytic conditions in order to mimic stress conditions. Result: The degradation products were well resolved from main peak and proving the stability-indicating power of the method. The developed method provided linear responses within the concentration range 1-5 µg/mL, and regression analysis showed a correlation coefficient value (r2) of 0.999. The HPLC method was validated as per ICH guidelines with respect to specificity, precision, linearity and robustness. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.25 µg/mL and 1.00 µg/mL respectively. Conclusion: The method provides good sensitivity and excellent precision and reproducibility. The method was highly selective, where degradation products and co formulated compounds did not interfere. The proposed method was successfully applied in pharmaceutical preparations.

scholarly journals Kinetics study of metaxalone degradation under hydrolytic, oxidative and thermal stress conditions using stability-indicating HPLC method

2012 ◽  
Vol 2 (6) ◽  
pp. 431-436 ◽  
Author(s):  
Vamsi Krishna Marothu ◽  
Rajendra N. Dash ◽  
Saritha Vemula ◽  
Shravani Donkena ◽  
Ramesh Devi ◽  
...  
Keyword(s):  
Thermal Stress ◽  
Hplc Method ◽  
Stress Conditions ◽  
Kinetics Study ◽  
Stability Indicating

scholarly journals Development of Stability Indicating RP-HPLC Method for Ertapenem in Bulk Drug and Pharmaceutical Dosage Form

2017 ◽  
Vol 16 (1) ◽  
pp. 21-28
Author(s):  
Ruchi Jain ◽  
Nilesh Jain ◽  
Deepak Kumar Jain ◽  
Avineesh Singh ◽  
Surendra Kumar Jain
Keyword(s):  
Dosage Form ◽  
Degradation Products ◽  
Hplc Method ◽  
Stress Conditions ◽  
Assay Method ◽  
Main Peak ◽  
Forced Degradation ◽  
Pharmaceutical Dosage Form ◽  
Stability Indicating ◽  
Bulk Drug

A simple, inexpensive, rapid and novel stability indicating isocratic HPLC method has been developed and validated for quantitative analysis of ertapenem sodium in the bulk drug and in pharmaceutical dosage form. An isocratic separation of ertapenem sodium was achieved on Hypersil BDS C18 column (4.6 x 250 mm, 5 ? particle size) as the stationary phase with a flow rate of 1.2 ml/min and using a UV detector to monitor the eluate at 298 nm. The mobile phase consisted of acetonitrile : water (60:40v/v) and pH adjusted 2.9 by othophosphoric acid enabled separation of the drug from its degradation products. The method was validated for linearity, accuracy (recovery), precision, specificity and robustness. The linearity of the method was satisfactory over the range 2-10 ?g/ml (correlation coefficient 0.999). Recovery of ertapenem sodium from the pharmaceutical dosage form ranged from 99.97 to 103.7%. Ertapenem sodium was subjected to stress conditions [hydrolysis (acid, base), oxidation, photolysis and thermal degradation] and the samples were analyzed by this method. The forceddegradation study with ertapenem sodium showed that it was degraded under basic condition. The drug was stable under the other stress conditions investigated. Ertapenem sodium was found to be less stable in solution state, whereas it was comparatively much stable in solid state. The degradation products were well resolved from main peak. The forced degradation study prove the stability indicating power of the method and therefore, the validated method may be useful for routine analysis of ertapenem sodium as bulk drug, in respective dosage forms, for dissolution studies and as stability indicating assay method in pharmaceutical laboratories and industries.Dhaka Univ. J. Pharm. Sci. 16(1): 21-28, 2017 (June)

scholarly journals Stability Indicating RP-HPLC Method For Determination Of Ketoconazole In Bulk Drug And In Tablet Dosage Form

2021 ◽  
Vol 001 (02) ◽  
Author(s):  
Shalin Parikh ◽  
Jayant Dave ◽  
Jayendrakumar Patel
Keyword(s):  
Dosage Form ◽  
Linear Regression Analysis ◽  
Hplc Method ◽  
Stress Conditions ◽  
Dihydrogen Phosphate ◽  
Pharmaceutical Dosage Form ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Bulk Drug

A simple, precise, accurate and sensitive isocratic stability indicating RP-HPLC method has been developed and validated for determination of Ketoconazole in bulk drug and pharmaceutical dosage form. Isocratic RP-HPLC separation was achieved on Agilent C8 (150 mm ?4.6 mm, 5 µm particle size) with the mobile phase 0.3 % Triaethylamine in 20 mM potassium dihydrogen phosphate buffer pH adjusted to 4.0: Acetonitrile (68:32 % v/v) at a flow rate 1.0 ml/min. The retention time of Ketoconazole was 8.97 ± 0.50 min. The method was validated for specificity, linearity, precision, accuracy and robustness. The linear regression analysis data of calibration curve showed good linearity in concentration range 10-60 ?g/ml. The Intraday and Interday precision were 0.59-1.11 % and 0.26-1.73 % RSD respectively. The accuracy was found to be 98.11-99.26 %. The drug was subjected to the stress conditions like hydrolysis, oxidation, photolysis and dry heat. The proposed method is found to be specific with respect to degradation product formed after Acidic hydrolysis, Oxidation, Thermal and Photolytic degradation. The Ketoconazole was found to be stable under neutral hydrolytic, thermal and photolytic stress conditions. Acidic, thermal, photolytic stress conditions showed degradation. The proposed chromatographic method can be used for estimation of drug during stress testing & formal stability studies.

scholarly journals Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Najmul Hasan ◽  
Mathurot Chaiharn ◽  
Sauleha Khan ◽  
Hira Khalid ◽  
Nawab Sher ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Stress Conditions ◽  
Dual Wavelength ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Stability Indicating ◽  
Physiological Fluid

A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a HibarμBondapak ODS C18column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method.

Study of Doxofylline and its Degradation Products in Bulk Drug by a Newly Developed Stability-Indicating HPLC Method

2013 ◽  
Vol 96 (4) ◽  
pp. 765-770 ◽  
Author(s):  
Priti S Patil ◽  
Purnima D Hamrapurkar ◽  
Mitesh D Phale ◽  
Masti I Desai ◽  
Sandeep B Pawar
Keyword(s):  
Uv Light ◽  
Degradation Products ◽  
Hplc Method ◽  
Stress Conditions ◽  
Base Hydrolysis ◽  
Assay Method ◽  
Good Resolution ◽  
Buffer Solution ◽  
Solution Ph ◽  
Stability Indicating

Abstract The purpose of this work was to study the stability behavior of doxofylline under different stress conditions and to develop a sensitive stability-indicating HPLC assay method. The stress conditions applied included heat, moisture, acid-base hydrolysis, oxidation, and UV light. The drug was particularly labile under oxidative and thermal stress conditions, with 58.40 and 53.90% degradation, respectively. Good resolution of drug from degradation products formed under stress conditions was achieved on a C18 column using 10 mM KH2PO4 buffer solution (pH 6) methanol (40 + 60, v/v) as the mobile phase (pH 7.2). The flow rate was 1 mL/min, and the detection wavelength was 273 nm. The method was validated for linearity, range, precision, accuracy, LOD, and LOQ. The RSD was found to be <2%. Since the method effectively separates the drug from its degradation products, it can be used as a stability-indicating method.

scholarly journals Stability-Indicating RP-HPLC Method for Assay of Silver Lactate

2011 ◽  
Vol 8 (2) ◽  
pp. 483-490
Author(s):  
V. Srinivasan ◽  
H. Sivaramakrishnan ◽  
B. Karthikeyan
Keyword(s):  
Thermal Stress ◽  
Degradation Products ◽  
Potassium Dihydrogen Phosphate ◽  
Hplc Method ◽  
Stress Conditions ◽  
Base Hydrolysis ◽  
Assay Method ◽  
Dihydrogen Phosphate ◽  
Stability Indicating ◽  
Rp Hplc

A simple, economic and time-efficient stability-indicating, reverse-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for analysis of silver lactate in the presence of degradation products generated by decomposition. When silver lactate was subjected to acid hydrolysis, base hydrolysis, oxidative, photolytic, humidity and thermal stress, degradation was observed during base hydrolysis, oxidation, humidity and thermal stress. The drug was found to be stable to other stress conditions. Successful chromatographic condition of the drug from the degradation products formed under stress conditions was achieved on a phenomenex Gemini column with potassium dihydrogen phosphate buffer, pH adjusted to 2.2 with orthophosphoric acid, as mobile phase. The method was validated for linearity, precision, specificity and robustness and can be used for quality-control during manufacture and assessment of the stability of samples of silver lactate. To the best of our knowledge, a validated stability-indicating LC assay method for silver lactate based on lactic acid is reported for the first time.

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