Degradation kinetics study of cabozantinib by a novel stability-indicating LC method and identification of its major degradation products by LC/TOF-MS and LC–MS/MS

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.

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Development and Validation of Stability Indicating LC-PDA Method for Mycophenolate Mofetil in Presence of Mycophenolic Acid and Its Application for Degradation Kinetics and pH Profile Study

Advances in Chemistry ◽

10.1155/2014/719385 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Vishnu P. Choudhari ◽

Anna Pratima G. Nikalje

Keyword(s):

Mycophenolate Mofetil ◽

Degradation Products ◽

Degradation Kinetics ◽

Oxidative Degradation ◽

Reversed Phase ◽

Hplc Method ◽

Design Tool ◽

Ph Profile ◽

Stability Indicating ◽

Specificity And Sensitivity

Factorial design tool applied for development of isocratic reversed-phase stability-indicating HPLC method for the analysis of mycophenolate mofetil (MMF) and its degradation products. MMF stress degradation products mycophenolate acid (MPA) and DP3 (USP impurity H) were isolated and used for quantitation. Separation achieved on a Symmetry C18 (250 mm × 4.6 mm, 5.0 μ) column using a methanol: acetate buffer (75 : 25 v/v), pH 6.0 (adjusted with acetic acid), at 0.5 mL flow rate, column maintained at 55°C, and data integrated at 251 nm. MMF is subjected to hydrolysis, oxidation, heat degradation, and so forth; under all these conditions degraded products are well separated. The method validation characteristics included accuracy, precision, linearity, range, specificity, and sensitivity. Robustness testing is conducted to evaluate the effect of minor changes to the chromatographic conditions and to establish appropriate system suitability parameters. The proposed method is used to investigate kinetics of acid, alkali hydrolysis and oxidation process. Major degradation products MPA and DP3 were isolated and quantitated. Characterization of MPA by NMR and LC-MS/MS and other degraded products by LC-MS/MS is attempted successfully. The method is used successfully for the quality assessment of three MMF drug commercial formations and its acid, alkali, and oxidative degradation kinetics study.

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Stability-indicating HPLC method development and structural elucidation of novel degradation products in posaconazole injection by LC–TOF/MS, LC–MS/MS and NMR

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2016.03.034 ◽

2016 ◽

Vol 125 ◽

pp. 165-177 ◽

Cited By ~ 6

Author(s):

Yidi Yang ◽

Xi Zhu ◽

Fei Zhang ◽

Wei Li ◽

Ying Wu ◽

...

Keyword(s):

Method Development ◽

Degradation Products ◽

Hplc Method ◽

Structural Elucidation ◽

Stability Indicating ◽

Hplc Method Development ◽

Tof Ms

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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

Journal of AOAC International ◽

10.5740/jaoacint.11-063 ◽

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.

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