Characterization of Degradation Products of Lifitegrast by Mass Spectrometry: Development and Validation of a Stability-indicating Reversed Phase HPLC Method

Kumar, Ajay; Chalannavar, Raju K.

doi:10.1080/22297928.2022.2159522

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…Stress studies were conducted under ICH‐recommended guidelines to evaluate the proposed analytical method's stability‐indicating property. Stress degradation studies of APR were carried out by subjecting the drug sample to acidic, basic, photolytic, oxidative, and heat conditions [46–50].…”

Section: Methodsmentioning

confidence: 99%

Novel Stability–Indicating Reverse‐Phase High‐Performance Liquid Chromatography Technique for Apremilast Quantification in Pharmaceuticals and Nanovesicular Systems: A Design of Experiment Approach

Sutar,

Jalalpure,

Kurangi

2024

Separation Science Plus

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An accurate and precise reverse‐phase high‐performance liquid chromatographic technique for apremilast (APR) quantification in bulk, commercial tablets, and formulated APR‐loaded nanoformulations was developed and validated by the design of the experiment approach in accordance with the International Conference of Harmonization guidelines. APR was separated by using formic acid buffer (0.1%; pH 3.2):methanol (40:60, v/v) as a solvent system with a flow rate of 1 mL/min and was detected at a wavelength of 230 nm with a retention time of 7.1 min. The central composite design was employed to optimize the developed analytical method. The calibration curve for APR was linear (r2 = 0.999), with a limit of detection of 0.5 µg/mL and a limit of quantification of 1.52 µg/mL, respectively. A recovery of APR in tablet and nanoformulation was observed in the 98.56%–99.32% range. Forced degradation studies revealed the stability of the proposed analytical method, as the APR peak remained unchanged under stress‐induced degradation experiments. Hence, the proposed chromatographic technique with a cost‐effective solvent system could be employed in the pharmaceutical industry for estimating APR in various formulations.

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Section: Methodsmentioning

confidence: 99%

Novel Stability–Indicating Reverse‐Phase High‐Performance Liquid Chromatography Technique for Apremilast Quantification in Pharmaceuticals and Nanovesicular Systems: A Design of Experiment Approach

Sutar,

Jalalpure,

Kurangi

2024

Separation Science Plus

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Acidic hydrolytic stability of the Lifitegrast: Degradation, Method development, Validation, Synthesis, LC-MS/NMR Characterization, In silico and In vitro cytotoxicity

Kandula,

Gantala,

Nishad

et al. 2024

Preprint

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In addition to the multiple vision problems, the toxicity of the degradation products of ophthalmic medications on eye health is today’s concern. Hence, degradation studies of ophthalmic drug and toxicity establishment of the degradation products have been considered. The manuscript includes simple, mass-compatible HPLC methodology and comprehensive protocol for forced degradation studies of the lifitegrast (LFT). Two degradants, (S)-2-(5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl) propanoic acid, (DP1) and benzofuran-6-carboxylicacid (DP2) were formed under acidic stress conditions. An accurate, robust HPLC method has been validated for routine quality control analysis of LFT. Theoretical quantum chemical calculations of reaction enthalpy were studied to explain the formation of DP1 and DP2. A synthesis scheme for DP1 was employed, and characterised using LC-ESI-MS, NMR techniques. The characterization of DP2 was conducted using various analytical advancements. By employing Swiss ADME software, the details of DPs concerning various physicochemical characteristics, and skin permeation capabilities were predicted. A DEREK prediction has revealed the meta-structures in the test molecules which have adverse toxicological properties. Human corneal epithelial (HCE) cell viability assessment upon treatment with LFT DPs revealed that the compound DP2 showed significant cytotoxicity at lower concentration (8 µg/mL) whereas DP1 showed significant toxicity only at higher concentrations (1280 µg/mL).

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Effect of Citric Acid and Tromethamine on the Stability of Eyedrops Containing Lifitegrast

Jeong,

Ha,

Park

et al. 2024

Pharmaceuticals

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Background/Objectives: Lifitegrast is an effective treatment for dry eye disease, reducing inflammation and improving the ocular surface condition. Owing to its high sensitivity to oxidation and hydrolysis, formulation studies are required to maintain the physicochemical stability of lifitegrast. This study aimed to overcome the instability of lifitegrast by developing a more stable eyedrop formulation by using citric acid and tromethamine to prevent the degradation of lifitegrast. Methods: Based on the Design of Experiment (DoE) approach, formulations were prepared at various concentrations of two stabilizers, citric acid and tromethamine. The stabilizers were carefully controlled to reduce the generation of degradation products. The eyedrops were stored under accelerated test conditions, and parameters such as appearance, pH, drug content, and impurities were evaluated. Results: The results showed that all critical quality attributes (CQAs) including appearance, pH, drug content, and impurities were maintained at stable levels under accelerated conditions, meeting established criteria. In addition, it was suggested that citric acid provided protection against oxidative stress, while tromethamine prevented hydrolysis caused by pH fluctuations. Conclusions: Consequently, it was concluded that the developed lifitegrast-containing eyedrop formulation exhibited improved physicochemical stability, validated through statistical analyses. These findings contribute to the development of stable eyedrops and provide a foundation for commercial production and clinical applications.

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Characterization of Degradation Products of Lifitegrast by Mass Spectrometry: Development and Validation of a Stability-indicating Reversed Phase HPLC Method

Cited by 3 publications

References 25 publications

Novel Stability–Indicating Reverse‐Phase High‐Performance Liquid Chromatography Technique for Apremilast Quantification in Pharmaceuticals and Nanovesicular Systems: A Design of Experiment Approach

Novel Stability–Indicating Reverse‐Phase High‐Performance Liquid Chromatography Technique for Apremilast Quantification in Pharmaceuticals and Nanovesicular Systems: A Design of Experiment Approach

Acidic hydrolytic stability of the Lifitegrast: Degradation, Method development, Validation, Synthesis, LC-MS/NMR Characterization, In silico and In vitro cytotoxicity

Effect of Citric Acid and Tromethamine on the Stability of Eyedrops Containing Lifitegrast

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