A new stability indicating ultra-fast liquid chromatographic (RP-UFLC) method for the quantification of Nilotinib – A drug for blood cancer

2021 ◽  
pp. 2581-2586
Author(s):  
Paladugu Venkata Naveen ◽  
Seru Ganapaty
Keyword(s):  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Forced Degradation ◽  
Chromatographic Study ◽  
Linear Regression Equation ◽  
Stability Indicating ◽  
Ich Guidelines ◽  
Forced Degradation Studies ◽  
Liquid Chromatographic ◽  
Alkaline Oxidation

Nilotinib hydrochloride monohydrate is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia. A new stability indicating ultra-fast liquid chromatographic (RP-UFLC) method was developed for the quantification of Nilotinib and validated. Mobile phase consisting of a mixture of sodium acetate (pH 5.0): acetonitrile (40: 60, v/v) was used with flow rate 0.8 mL/min (UV detection at 254 nm) for the chromatographic study. Nilotinib obeys Beer-Lambert’s law over the concentration range of 0.2-80 μg/mL (R2 = 0.9999) with linear regression equation y = 175336x +20675. The LOQ was found to be 0.1897 μg/mL and the LOD was found to be 0.0619 μg/mL. Forced degradation studies were performed such as acidic, alkaline, oxidation and thermal degradations and the method was validated as per ICH guidelines.

A new Validated Stability Indicating RP-UFLC Method for the Estimation of Voriconazole in presence of internal standard

2021 ◽  
pp. 4825-4831
Author(s):  
Paladugu Venkata Naveen ◽  
Seru Ganapaty
Keyword(s):  
Fungal Infections ◽  
Internal Standard ◽  
Kinetic Studies ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Ich Guidelines ◽  
Liquid Chromatographic Method ◽  
Forced Degradation Studies ◽  
Anti Fungal ◽  
Liquid Chromatographic

Voriconazole is used for the treatment of variety of fungal infections caused by aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis etc. Voriconazole belongs to triazole class. Voriconazole is mainly used to treat certain patients who are not responding to other anti-fungal drugs. It works by slowing the growth of the fungi that cause infection. A new validated reverse phase stability indicating liquid chromatographic method has been developed for the assay of Voriconazole in presence of an internal standard (Rufinamide) tablets. Forced degradation studies were performed to define the selectivity and specificity of the method. Linearity was observed over the concentration range 1.0-100μg/mL with linear regression equation y = 0.4489x – 0.1262 (r2 = 0.9999). The LOQ and LOD were found to be 0.8934μg/mL and 0.2921μg/mL. The present stability indicating RP-UFLC method was validated as per ICH guidelines and can be useful for the assay of tablets and injections and also for the kinetic studies.

scholarly journals FORCED DEGRADATION STUDIES OF NILOTINIB HYDROCHLORIDE: ISOLATION, IDENTIFICATION & CHARACTERIZATION OF IMPURITIES

2020 ◽  
pp. 537-543
Author(s):  
JCMKNN Murty Singamsetti ◽  
Raghu Babu Korupolu ◽  
Himabindhu Gandham ◽  
Mahesh Kumar Reddy Geereddi ◽  
Muralidharan Kaliyaperumal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Degradation Product ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Myelogenous Leukemia ◽  
Forced Degradation ◽  
Molecular Formula ◽  
Forced Degradation Studies ◽  
Acidic Environments ◽  
Degradation Studies

Nilotinib hydrochloride is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia was subjected to forced degradation studies and the samples were analyzed by utilizing the LCMS compatible HPLC methods. Nilotinib Hydrochloride was subjected to thermal, hydrolytic, oxidative, acidic, basic and photolytic degradation conditions as per the regulatory guidelines. The drug was degraded in oxidative, basic and acidic environments and stable in photolytic and thermal conditions. The main degradation impurity components produced through the forced degradation study were isolated for the identification and quantification in presence of these impurities in the stability studies of drug substances as well as drug products. The identified degradation components were separated by mass assisted auto-purification technique and subjected for the characterization by NMR (13C-NMR, 1H-NMR, HMBC and HSQC), HRMS and FT-IR experimentations. Degradation products obtained from oxidative, basic and acidic environments were isolated and identified by the advanced techniques  as acid degradation product (DP-1) with molecular mass of 306.11 g/mol, empirical formula C17H14N4O2 with name as 4-methyl-3- (4 -(pyridine -3-yl) pyrimidin -2 -ylamino) benzoic acid. Base degradation product (DP-2) has molecular weight of 241.08 g/mol, molecular formula C11H10F3N3 with name as 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline.Oxidative degradation product (DP-3) has molecular weight of 545.18 g/mol, molecular formula C28H22F3N7O2 with name as 3-(2-(2-methyl-5-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenylcarbamoyl) phenylamino)pyrimidin-4-yl)pyridine1-oxide.  

scholarly journals LC-MS/MS CHARACTERIZATION OF FORCED DEGRADATION PRODUCTS OF TUCATINIB, A NOVEL TYROSINE KINASE INHIBITOR: DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD

2022 ◽  
pp. 58-66
Author(s):  
S. K. REEHANA ◽  
K. SUJANA
Keyword(s):  
Kinase Inhibitor ◽  
Degradation Products ◽  
Degradation Pathway ◽  
Hplc Method ◽  
Forced Degradation ◽  
Ich Guidelines ◽  
System Suitability ◽  
Forced Degradation Studies ◽  
Development And Validation

Objective: The current study focused on the development, validation, and characterization of forced degradation products using LC-MS/MS. Methods: A simple, selective, validated and well-defined isocratic HPLC methodology for the quantitative determination of Tucatinib at a wavelength of 239 nm. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6 mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 ml/min. MS/MS was used to characterize degradation products formed in the forced degradation study. The validation and characterization of forced degradation products were performed in accordance with ICH guidelines. Results: Over the concentration range of 5-100μg/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. According to standard guidelines, the method was quantitatively evaluated in terms of system suitability, linearity, precision, accuracy, and robustness, and the results were found to be within acceptable limits. The drug was degraded under acidic, alkaline, and reduction conditions in forced degradation studies. Conclusion: The method was found to be applicable for routine tucatinib analysis. Because no LC-MS/MS method for estimating tucatinib and its degradation products has been reported in the literature. There is a need to develop a method for studying the entire tucatinib degradation pathway.

scholarly journals Stability-indicating HPLC-DAD method for the determination of empagliflozin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shilpi Pathak ◽  
Pradeep Mishra
Keyword(s):  
Hplc Method ◽  
Coefficient Of Determination ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Ich Guidelines ◽  
Validation Parameters ◽  
Forced Degradation Studies ◽  
Tablet Dosage

Abstract Background A stability-indicating RP-HPLC method was developed and validated for the estimation of empagliflozin drug and its tablet dosage form using a DAD detector. The mobile phase consisted of methanol/acetonitrile/0.1%OPA (75:20:5). The peak was observed at 2.54 min using 222.0 nm absorption maxima. Results Calibration curve plot was found within the range of 10–50 µg/mL. The coefficient of determination (R2) was found to be 0.9990. Forced degradation studies were performed for the empagliflozin in various conditions, and the results were calculated as %RSD values and were found to be within the limits. Conclusion The method was validated as per ICH guidelines with respect to all validation parameters.

scholarly journals Analysis of Chromium (III)Picolinate in Capsule dosage form by using Stability indicating HPTLC Method

2019 ◽  
Vol 12 (6) ◽  
pp. 101-108
Author(s):  
Aditi R. Kakade ◽  
Savita Yadav
Keyword(s):  
Nutritional Supplement ◽  
Chromium Picolinate ◽  
Forced Degradation ◽  
Capsule Formulation ◽  
Stability Indicating ◽  
Ich Guidelines ◽  
Forced Degradation Studies ◽  
Method Optimization ◽  
Degradation Studies ◽  
Hptlc Method

Chromium (III) picolinate is used as a nutritional supplement and has been valuable effects on carbohydrate and lipid metabolism alleviating symptoms associated with diabetes. A chromium supplement produces beneficial results in reducing insulin sulfonylurea or metformin requirements. Hence, stability indicating HPTLC method was developed for estimation of Chromium picolinate in capsule formulation. The development of HPTLC method optimization on precoated silica gel 60 F254 aluminium plates of 20 cm x 20 cm, 250μm thickness. The mobile phase used was methanol: ethyl acetate6:4 (v/v). The densitometry detection was done at 264 nm. Also, the forced degradation studies were performed and method was validated with as per ICH guidelines. The Rf value obtained was 0.39 ±0.05.Linearity data for the calibration curve gave a good linear relationship over the concentration range of 100-600ng/spot for Chromium picolinate (correlation coefficient R2 =0.9997). The percent recovery of Chromium picolinate in marketed formulation was found in the range of 99.56%.Force degradation and validation of method was done as per ICH guidelines and the results are within the compliance limit.The developed HPTLC method gave good results for force degradation studies show that the method is stability indicating. Thus, this method can be used for routine analysis of Chromium picolinate and can be use for its future usage

scholarly journals A Stability-Indicating RP-HPLC-UV Method for Determination and Chemical Hydrolysis Study of a Novel Naproxen Prodrug

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed H. M. Hamid ◽  
Tilal Elsaman
Keyword(s):  
Oral Delivery ◽  
Hplc Method ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Chemical Hydrolysis ◽  
Ich Guidelines ◽  
Forced Degradation Studies ◽  
The Stability ◽  
Average Retention Time

A new naproxen amide prodrug was synthesized and spectrally characterized and a simple, precise, and accurate stability-indicating RP-HPLC method was developed and validated for determination and chemical hydrolysis study of the prodrug. Forced degradation studies were conducted as per the International Conference on Harmonization (ICH) guidelines to establish the stability-indicating power of the method. Separations were performed on a C18 column (150 × 4.6 mm i.d., 5 μm p.s.). The mobile phase consisted of acetonitrile and phosphate buffer pH 4.0 in the ratio 60 : 40. The flow rate and injection volume were 1.0 mL/min and 15 μL, respectively. The peaks were monitored at 272 nm. The average retention time is 5.136 min. The linearity of the method was investigated in the range of 10–50 μg/mL and r2 was found to be larger than 0.9987. The LOD and LOQ were found to be 1.853 and 5.615 μg/mL, respectively. Results indicated that the degradants are well resolved and separated from the prodrug. Hydrolysis kinetics studies were carried out in buffer solutions (pH 1.2, 5.5 and 7.4) to establish the fate of the prodrug. The half-lives in the respective buffers were 23.5, 262, and 334 hours indicating sufficient stability to attain the goal of oral delivery.

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

2016 ◽  
pp. 242 ◽  
Author(s):  
V. Ashok Chakravarthy ◽  
Sailaja Bbv ◽  
Praveen Kumar A
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Dosage Forms ◽  
Forced Degradation ◽  
Reverse Phase ◽  
Stability Indicating ◽  
Liquid Chromatographic Method ◽  
Forced Degradation Studies ◽  
Tablet Dosage ◽  
Liquid Chromatographic

<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 &lt;5%.<br />The correlation coefficient found for all compounds was not &lt;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>

APPLICATION OF EXPERIMENTAL DESIGNS FOR OPTIMIZATION OF FORCED DEGRADATION STUDIES AND DEVELOPMENT OF STABILITY-INDICATING HPTLC METHOD FOR COMBINATION OF CEFPODOXIME PROXETIL AND OFLOXACIN

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (07) ◽  
pp. 49-58
Author(s):  
V. T Gawande ◽  
K. G Bothara
Keyword(s):  
Fixed Dose ◽  
Forced Degradation ◽  
Cefpodoxime Proxetil ◽  
Stability Indicating ◽  
Ich Guidelines ◽  
Tlc Plates ◽  
Forced Degradation Studies ◽  
Dose Combination ◽  
Degradation Studies ◽  
Hptlc Method

A stability indicating HPTLC method was developed and validated for fixed dose combination of cefpodoxime proxetil and ofloxacin. TLC plates precoated with silica gel 60F254 were used as stationary phase and n propanol: ammonia (7:3 v/v) was used as mobile phase. Densitometric scanning was carried out at 290nm. Specificity of the method was established by peak purity studies. Method was validated as per ICH guidelines Q2 (R1) for accuracy, precision, linearity, sensitivity and robustness. Both the drugs were subjected to hydrolytic (acidic and basic), oxidative, thermal and photolytic stress as per ICH guidelines Q1A (R2) and Q2B. Forced degradation studies were performed by using design of experiments approach, the most widely used mathematical model. Such experimental design approach can replace conventional trial and error experimentation to achieve optimum degradation.

scholarly journals Stability indicating thin-layer chromatographic method for estimation of antidiabetic drug Remogliflozin etabonate

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dimal A. Shah ◽  
Ishita I. Gondalia ◽  
Vandana B. Patel ◽  
Ashok Mahajan ◽  
Usmangani Chhalotiya ◽  
...  
Keyword(s):  
Thin Layer ◽  
High Performance ◽  
Chromatographic Method ◽  
Tablet Formulation ◽  
Base Hydrolysis ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Forced Degradation Studies ◽  
Degradation Studies ◽  
Remogliflozin Etabonate

Abstract Background A sensitive, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method has been developed for the analysis of Remogliflozin etabonate in tablet formulation. HPTLC plates precoated with silica gel 60 F254 were used as the stationary phase; methanol: ethyl acetate: toluene: NH3 (2:4:4:0.1, v/v/v) was used as mobile phase, and densitometry was used for the quantitative estimation of the drug. The proposed method was validated with respect to linearity, accuracy, precision, and robustness and applied for the estimation of drug in tablet dosage form. Results The Rf value of Remogliflozin etabonate was observed to be 0.61. The densitometric estimation was performed in reflectance mode at 229 nm. The method was found to be linear in the range of 500–8000 ng/band for Remogliflozin etabonate. The possible degradation pathway was estimated by performing forced degradation studies. The degradant peaks were well resolved from the drug peak with acceptable resolution in their Rf value. Conclusion An accurate and precise high-performance thin-layer chromatographic method has been developed for the quantification of Remogliflozin etabonate in tablets. Forced degradation studies were performed, and drug was found to be highly susceptible to acid, base hydrolysis, and oxidative stress degradation and gets converted into active drug Remogliflozin. Both Remogliflozin etabonate and Remogliflozin bands were well resolved. The method was applied for the analysis of drug in tablet formulation, and it can be used for routine quality control analysis, as well as for the analysis of stability samples.

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