Degradation Products In Tablets Research Articles

Stability-indicating RP-UPLC method for determination of antihypertensive drugs and their degradation products in tablets: application to content uniformity and dissolution studies

Stability-indicating RP-UPLC method for determination of antihypertensive drugs and their degradation products in tablets: application to content uniformity and dissolution studies

Stability-indicating HPLC method for determination of amiodarone hydrochloride and its impurities in tablets: a detailed forced degradation study

Resumo Amiodarone hydrochloride is one of the most important drugs used to treat arrhythmias. The USP monograph for amiodarone hydrochloride describes an HPLC method for the quantification of seven impurities, however, this method shows problems that result in unresolved peaks. Moreover, there is no monograph for tablets in this compendium. Thus, a stability indicating HPLC method was developed for the determination of amiodarone, its known impurities and degradation products in tablets. A detailed forced degradation study was performed submitting amiodarone API, tablets and placebo to different stress conditions: acid and alkaline hydrolysis, oxidation, metal ions, heat, humidity, and light. Amiodarone hydrochloride API was susceptible to degradation in all stress conditions. The tablets also showed degradation in all environments, except in acidic condition. The analytes separation and quantification were achieved on an Agilent Zorbax Eclipse XDB-C18 column (100 x 3.0 mm, 3.5 µm). The mobile phase was composed of 50 mM acetate buffer pH 5.5 (A) and a mixture of methanol-acetonitrile (3:4, v/v) (B) in gradient elution. The method was validated in the range of 350-650 µg/mL for assay and 10-24 µg/mL for impurities determination. Therefore, this method can be used both for stability studies and routine quality control analyses.

Application of Validated UPLC/Q-TOF-MS Method for Simultaneous Determination of Telmisartan, Hydrochlorothiazide and their Degradation Products in Tablets

Application of Validated UPLC/Q-TOF-MS Method for Simultaneous Determination of Telmisartan, Hydrochlorothiazide and their Degradation Products in Tablets

Development and validation of HPLC and CE methods for simultaneous determination of amlodipine and atorvastatin in the presence of their acidic degradation products in tablets.

Two methods were developed for separation and quantitation of amlodipine (AML) and atorvastatin (ATV) in the presence of their acidic degradation products. The first method was a simple isocratic RP-HPLC method while the second was capillary electrophoresis (CE). Degradation products were obtained by acidic hydrolysis of the two drugs and their structures were elucidated for the first time by IR and MS spectra. Degradation products did not interfere with the determination of either drug and the assays were therefore stability-indicating. The linearity of the proposed methods was established over the ranges 1-50 μg mL-1 for AML and ATV in the HPLC method and in the range of 3-50 and 4-50 μg mL-1 for AML and ATV, respectively, in the CE method. The proposed methods were validated according to ICH guidelines. The methods were successfully applied to estimation of AML and ATV in combined tablets.

STABILITY INDICATING REVERSE PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD FOR SIMULTANEOUS ESTIMATION OF LABETALOL AND ITS DEGRADATION PRODUCTS IN TABLET DOSAGE FORMS

<p>ABSTRACT<br />Objective: The objective of the present work is to develop a simple, efficient, and reproducible stability indicating reverse phase high-performance<br />liquid chromatographic method for simultaneous determination labetalol and its degradation products in tablet dosage forms.<br />Methods: The chromatographic separation of labetalol and its degradation products in tablets was carried out on Zorbax Eclipse Plus C-18<br />(100 × 4.6 mm, 3.5 µm) column using 0.1% trifluoroacetic acid (TFA) (v/v) in 1000 ml of water and 0.1% TFA (v/v) in 1000 ml of acetonitrile:<br />Methanol (1:1) by linear gradient program. Flow rate was 1.0 mL min<br /> with a column temperature of 35°C, and detection wavelength was carried out<br />at 230 nm. Known impurity is well resolved from the main active drug within 14 minutes run time.<br />−1<br />Results: The forced degradation studies were performed on labetalol tablets under acidic, basic, oxidation, thermal, humidity, and photolytic<br />conditions. No degradation products were observed from the forced degradation studies, and the known impurity is well resolved from the main<br />active drug. The method was validated in terms of specificity, linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, and<br />robustness as per the ICH guidelines. The method was found to be linear in the range of LOQ to 120% for all the known and unknown impurities.<br />The LOD and LOQ values of known impurity were found between 0.3593 and 0.7187 µg mL<br />, and the percentage recovery values were in the range<br />of 95.5-105.2% at different concentration levels. Relative standard deviation for precision and intermediate precision results were found to be <5%.<br />The correlation coefficient found for all compounds was not <0.99. The results obtained from the validation experiments prove that the developed<br />method is a stability indicating method.<br />−1<br />Conclusion: The developed method can be successfully applied for routine analysis, quality control analysis and also suitable for stability analysis of<br />the simultaneous determination of labetalol and its degradation products in tablet dosage forms as per the regulatory requirements.<br />Keywords: Labetalol, Development, Validation, Reverse phase high-performance liquid chromatography.</p>

Development and Validation of an RP-HPLC Method for Estimation of Cefuroxime Axetil and Its Degradation Products in Tablets

A simple precise specific sensitive and accurate stability indicating RP-HPLC method for determination of cefuroxime Axetil and its degradation products in tablets. The separation was performed on Teknokroma, tracer excel C8 column (15cm x 0.46cm.5μm) using mobile phase consisting of 0.02M potassium dihydrogen phosphate: methanol: Acetonitrile (60: 35: 5 v/v). The flow rate was 1mL/min and detection was monitored at 278nm. The column temperature was set at 35℃. The retention times were 2.4, 11.09, 12.6, 12.6, 14.13, 20.76 and 24.24 minutes for cefuroxime Axetil B, cefuroximeA A, ∆^3-isomers, E-isomer 1 and E-isomer 2, respectively. The calibration curves were found to be linear in the concentration range of 120-312 μg/mL (r2 =0.99964) and 0.24-7.2 μg/mL (r2 =0.9997) at assay level and low-level of cefuroxime Axetil. The percentage recoveries of cefuroxime Axetil at assay level were found to be in the range of 98.54-99.35% and 101.4-103.69% at low-level at 95% confidence limit. The intraday precision was 0.517% and 2.019% at to assay level and low-level of CFA, respectively. The intermediate precisions were 1.102% and 2.273% at assay level and low-level of CFA, respectively.

Stability-Indicating HPLC-DAD Method for the Determination of Linagliptin in Tablet Dosage Form: Application to Degradation Kinetics.

This work aims to develop HPLC-DAD method for linagliptin (LNG) quantitation in the presence of its degradation products in tablets and to study its degradation kinetics. LNG samples were extracted from tablets and diluted. Various ICH degradation conditions were applied to study LNG degradation kinetics. LNG was assayed by a C18 column using a simple isocratic mobile phase (methanol:water containing 0.3% TEA, 40:60, pH 4.5) pumped at 1 mL/min. The drug was detected at 225 nm. The method showed high linearity (r2 > 0.999) with CV% and % error of the mean <2% over the range of 1-50 μg/mL. Limits of detection and quantitation were 0.3 and 1.0 μg/mL, respectively. LNG retention time was 11 min with a total run time of 17 min. In all degradation conditions applied, LNG was well separated from its degradation products. The method was successfully used to quantitate LNG content in its tablets and study its degradation kinetics in acidic, alkaline and oxidative forced degradation experiments. In conclusion, simple, precise and reliable method for the separation and determination of LNG in the presence of its degradation products under different stress conditions was developed and validated according to the latest ICH guidelines.

Development and Validation of an RP-HPLC Method for Estimation of Secnidazole and Its Degradation Products in Tablets

Development and Validation of an RP-HPLC Method for Estimation of Secnidazole and Its Degradation Products in Tablets

Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Enrofloxacin and Its Degradation Products in Tablet Dosage Forms.

The present work was the development of a simple, efficient, and reproducible stability-indicating reverse-phase high performance liquid chromatographic (RP-HPLC) method for simultaneous determination enrofloxacin (EFX) and its degradation products including ethylenediamine impurity, desfluoro impurity, ciprofloxacin impurity, chloro impurity, fluoroquinolonic acid impurity, and decarboxylated impurity in tablet dosage forms. The separation of EFX and its degradation products in tablets was carried out on Kromasil C-18 (250 × 4.6 mm, 5 μm) column using 0.1% (v/v) TEA in 10 mM KH2PO4 (pH 2.5) buffer and methanol by linear gradient program. Flow rate was 1.0 mL min−1 with a column temperature of 35°C and detection wavelength was carried out at 278 nm and 254 nm. The forced degradation studies were performed on EFX tablets under acidic, basic, oxidation, thermal, humidity, and photolytic conditions. The degraded products were well resolved from the main active drug and also from known impurities within 65 minutes. The method was validated in terms of specificity, linearity, LOD, LOQ, accuracy, precision, and robustness as per ICH guidelines. The results obtained from the validation experiments prove that the developed method is a stability-indicating method and suitable for routine analysis.

Simultaneous Analysis of Losartan Potassium and its Related Impurities and Degradation Products in Tablets Using HPLC

A simple, sensitive, precise and reliable gradient HPLC method was developed and validated for simultaneous quantitative determination of losartan potassium and its eleven related impurities and degradation products in a tablet formulation. Among them B, C, D, E, F, I and G were related impurities and J, K, L and M were degradation products. Optimum chromatographic separation was carried out on an ACCHROM ODS-C18 (250 mm×4.6 mm, 5 µm) column using mobile phases consisting of acetonitrile and 0.1% phosphoric acid under a gradient elution program. The UV detection wavelength was performed at 220 nm with a flow rate of 1.0 mL/min. The column temperature was maintained at 35 °C. All standard curves obtained exhibited good linear regression (r > 0.9995) within the tested range. All the average recovery rates were in the range of 97.00-103.00% and RSD was less than 2.00% (n = 3). Limits of detection and quantification were determined in the level of ng/mL. The results demonstrated that the validated method was suitable for the simultaneous quantification of losartan potassium and its eleven related impurities and degradation products in a tablet formulation. Keywords: HPLC, losartan potassium, related impurities and degradation products, simultaneous quantitative determination.

VALIDATED UPLC/Q-TOF-MS METHOD FOR SIMULTANEOUS DETERMINATION OF ACECLOFENAC, PARACETAMOL, AND THEIR DEGRADATION PRODUCTS IN TABLETS

A fast, sensitive, and specific ultra-performance liquid chromatography/quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) method has been developed and validated for the simultaneous determination of aceclofenac, paracetamol, and their major degradation products in tablets. Diclofenac and para-aminophenol as the potential degradation product of aceclofenac and paracetamol, respectively, were analyzed. The chromatographic separation was achieved on Acquity UPLC BEH C18 (100.0 × 2.1 mm, 1.7 µm) column using isocratic mobile phase consisting of acetonitrile-2 mM ammonium acetate (40:60, v/v) at a flow rate of 0.25 mL/min. The Q-TOF mass spectrometer was operated in positive ionization mode and quantitation was done using the MS/MS transitions m/z 354.07 → 215.07 for aceclofenac, 296.23 → 214.06 for diclofenac, 152.07 → 110.06 for paracetamol, and 110.07 → 65.04 for para-aminophenol. The elution of aceclofenac, diclofenac, paracetamol, and para-aminophenol occurred at 1.50, 1.05, 0.61, and 1.61 min, respectively. The calibration curves were linear over the concentration range of 1–1000 ng/mL for aceclofenac and paracetamol, 0.01–1 ng/mL for diclofenac and 0.01–5 ng/mL for para-aminophenol. The developed method was validated according to ICH guidelines. The proposed method can be applied for determination of aceclofenac and paracetamol during routine quality control analysis and in stability studies to monitor the level of their degradation products in bulk drugs or in pharmaceutical formulations.

Stabilization by meglumine of an amine compound degraded by formaldehyde in tablets

[3-[(2R)-[[(2R)-(3-Chlorophenyl)-2-hydroxyethyl]amino]proryl]-1 H-indol-7-yloxy]acetic acid (AJ-9677), which was being developed as an antidiabetic, was observed to degrade in tablet preparations. The main degradation product in tablets, AD-9889, was a carbon adduct of the drug substance. When the drug substance was exposed to formaldehyde in aqueous solutions, a correlation was found between the level of formaldehyde and the quantity of AD-9889 formed during storage. Comprehensive one- and two-dimensional NMR analysis of the reaction product identified the location of the carbon atom which originated from formaldehyde, thus proving that AD-9889 was produced by a reaction with formaldehyde. Since it was demonstrated in our previous report that meglumine is an amine that can react with, and reduce amounts of formaldehyde, its stabilizing effect on AJ-9677 was examined. The results showed that in a solution system containing AJ-9677, formaldehyde and meglumine, meglumine reduced formaldehyde levels and suppressed degradation. Addition of meglumine into the tablet formulation of AJ-9677 was also effective in suppressing degradation and successfully stabilized the drug substance. This effect was almost certainly due to meglumine absorbing formaldehyde from around the drug substance and we believe that meglumine can be used with many other drug substances degraded by formaldehyde.

TLC-UV and -VIS Densitometric Detection Method for Determination of Oxyphenonium Bromide and its Degradation Products in Tablets

A chromatographic-densitometric method was developed for determination of oxyhyphenonium bromide and its degradation products under UV/VIS spectra. Silica gel TLCF254 plates were used as stationary phase and butanol-1–glacial acetic acid–water (12.8:2:2.8 v/v/v) as mobile phase. Densitometric measurements were done at λ ≈ 225 nm and λ ≈ 530 nm. Degradation products α-cyclohexyl-α-hydroxybenzeneacetic acid and N,N-diethyl-N-methylaminethanol were determined by 1HNMR method. The chromatographic-densitometric method is specific for studied compounds. Besides, it is shown that this method is very sensitive, precise, and has a broad range of linearity.

Stability indicating UPLC method for simultaneous determination of atorvastatin, fenofibrate and their degradation products in tablets

A stability indicating UPLC method was developed and validated for the simultaneous determination of atorvastatin, fenofibrate and their impurities in tablets. The chromatographic separation was performed on acquity UPLC™ BEH C18 column (1.7 μm, 2.1 mm × 100 mm) using gradient elution of acetonitrile and ammonium acetate buffer (pH 4.7; 0.01 M) at flow rate of 0.5 ml/min. UV detection was performed at 247 nm. Total run time was 3 min within which main compounds and six other known and major unknown impurities were separated. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated for accuracy, repeatability, reproducibility and robustness. Linearity, LOD and LOQ was established for atorvastatin, fenofibrate and their known impurities.

Stability-Indicating Method for Determination of Oxyphenonium Bromide and Its Degradation Product by High-Performance Liquid Chromatography

A high-performance liquid chromatographic (HPLC) method was developed for determination of oxyphenonium bromide (OX) and its degradation product. The method was based on the HPLC separation of OX from its degradation product, using a cyanopropyl column at ambient temperature with mobile phase of acetonitrile-25 mM potassium dihydrogen phosphate, pH 3.4 (50 + 50, v/v). UV detection at 222 nm was used for quantitation based on peak area. The method was applied to the determination of OX and its degradation product in tablets. The proposed method was also used to investigate the kinetics of the acidic and alkaline degradation of OX at different temperatures, and the apparent pseudo first-order rate constant, half-life, and activation energy were calculated. The pH-rate profile of the degradation of OX in Britton-Robinson buffer solutions within the pH range 2-12 was studied.

Membrane Sensors for the Selective Determination of Tiapride in Presence of its Degradation Products

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for determination of tiapride in presence of its degradation products are described. The sensors are based on the ion association complexes of tiapride cation with sodium tetraphenyl borate (Tia-TPB) [sensor 1]) or ammonium reineckate (Tia-R) [sensor 2] counter anions as ion exchange sites in PVC matrix. The performance characteristics, sensitivity and selectivity of these electrodes in presence of tiapride degradation products were evaluated according to IUPAC recommendations. It reveals a fast, stable and linear response for tiapride over the concentration range 10(-5)-10(-2) M with cationic slopes of 28.997 and 30.580 mV per concentration decade with sensors 1 and 2, respectively. These sensors exhibit fast response time (20-30 s), low quantitation limit (4.5x10(-6) and 3.6x10(-6), respectively), and good stability (6-8 weeks). The direct potentiometric determination of tiapride hydrochloride using the proposed sensors gave average recoveries of 99.95+/-0.678 and 99.92+/-1.157 for sensors 1 and 2, respectively. The sensors are used for determination of tiapride hydrochloride, in pure form, in presence of its degradation products in tablets, and in plasma. Validation of the method shows suitability of the proposed sensors for use in the quality control assessment of tiapride hydrochloride and for routine analysis as stability indicating method. The developed method was found to be simple, accurate and precise when compared with a reference company spectrophotometric method.

Isolation, identification and determination of the major degradation product in alprazolam tablets during their stability assay

The presence of a degradation product of alprazolam tablets that emerged throughout a short-stability assay has been determined and properly characterized. For this purpose an efficient methodology has been successfully applied, including SPE and HPLC methods for isolation and purification, respectively. LC/MS, MS/MS, 1H NMR, 13C NMR, UV and IR have been employed for structural elucidation confirming the identity of this impurity as 7-chloro-1-methyl-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-4-amine or triazolaminoquinoleine. The impurity, previously described as a long-term photodegradation product of alprazolam active pharmaceutical ingredient, was rapidly formed in the absence of light, but required the presence of excipients and its rate of formation increased with heat and humidity. In addition, a LC method has been developed and validated including triazolaminoquinoleine for the adequate determination of alprazolam and its mayor degradation product in tablets as pharmaceutical forms.

Application of High Performance Liquid Chromatography in the Determination of Tauromustine in Presence of Its Metabolites and Degradation Products

Abstract A reversed phase high performance liquid chromatography (HPLC) method was developed for the determination of tauromustine (TM) in presence of its metabolited in biological fluids and its degradation products in tablets. The proposed HPLC method was conducted using a lichrosorb C18 column [250 × 4 mm], with acetonitrile - water - acetate buffer pH5 (40: 55: 5) eluent, the detection was affected at 235 nm. The detector response was linear in the range 0.2–4 μg/ml for TM with minimum detectability (S/N=2) of 2 ng/ml. The proposed HPLC method was applied to the determination of TM in presence of its metabolites in biological fluids. The percentage recoveries of TM and its metabolites from spiked urine range from 93.1 to 92.9 and for plasma 90.3 to 89.6. The proposed HPLC method was used to study the kinetics of degradation of TM in standard solution as a function of temperature and alkalinity. TM degraded followed first-order kineties in agreement with the Arrhenius theory. The proposed HPLC method w...

Determination of pyridostigmine and the main degradation product in tablets by high-performance liquid chromatography

A high-performance liquid Chromatographic (HPLC) method for quantification of pyridostigmine bromide and its major degradation product, 3-hydroxy-1-methylpyridinium bromide, in tablets has been developed. The method involves the use of a polymeric column with acetonitrile-water (7.8:92.2 v/v) mixture and an ion-pair reagent as mobile phase. With the injection of 4.7 μg pyridostigmine bromide the limit of quantitation of the major degradation product is 0.01 μg which corresponds to 0.21% degradation. Blister packs of tablets from a single batch number, which had been stored under different conditions in Norway and Saudi Arabia, were analysed. Degradation was determined to be 1.4–1.6%. The age of the batch was about 3 years. The method is well suited for accelerated kinetic studies and routine control of aged pyridostigmine tablets.