Identification, Isolation, and Structural Characterization of Novel Forced Degradation Products of Darunavir Using Advanced Analytical Techniques Like UPLC–MS, Prep-HPLC, HRMS, NMR, and FT-IR Spectroscopy

Modini, Arun Kumar; Ranga, Mahesh; Puppala, Umamaheshwar; Kaliyapermal, Muralidharan; Geereddy, Mahesh Kumar Reddy; Samineni, Ramu; Grover, Parul; Konidala, Sathish Kumar

doi:10.1007/s10337-022-04226-z

Cited by 6 publications

(2 citation statements)

References 11 publications

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“…The method precision procedure was carried out by different analysts, on different days, using different instruments, and different columns. % RSD of results was calculated, and overall % RSD of method precision and intermediate precision results was also calculated (Modini et al, 2023).…”

Section: Methodsmentioning

confidence: 99%

Forced degradation and stability assessment of Tenofovir alafenamide

Kumar,

Malik

2023

DPSA

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This study presents a comprehensive evaluation of an analytical method for the quantification and identification of Tenofovir Alafenamide (TAF) and its related impurities in pharmaceutical formulations. The method exhibited outstanding performance, with exceptional sensitivity demonstrated through low limits of detection (LOD) and quantification (LOQ) values for TAF and various impurities. The LOD and LOQ values for TAF were determined to be 0.001% and 0.004%, respectively, underscoring the method's capability to detect minute concentrations. System suitability assessments, including LOD verification, linearity studies, relative response factor (RRF) determination, and accuracy assessments, provided a comprehensive understanding of the method's reliability and precision. The method showed a strong linear relationship between concentration and peak area, along with accurate recovery of added compound amounts at various concentration levels. Forced degradation studies further validated the method's specificity and robustness, with degradation peaks distinct from TAF and its specified impurities. Peak purity analysis confirmed the method's ability to accurately determine TAF in both untreated and treated test preparations. Additionally, system precision, method precision, and intermediate precision evaluations showcased the method's consistent and reproducible performance under various conditions and across different analysts. Stability assessments of the analytical solution, standard preparation, and mobile phase revealed the method's resilience to variations in flow rate and column oven temperature, with most parameters remaining within acceptable limits. In conclusion, this analytical method is a reliable tool for the precise quantification and identification of TAF and related impurities, meeting stringent acceptance criteria. Its robustness, precision, and specificity make it suitable for pharmaceutical quality control and research applications.

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Section: Methodsmentioning

confidence: 99%

Forced degradation and stability assessment of Tenofovir alafenamide

Kumar,

Malik

2023

DPSA

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“…(3) NMR spectra can often provide more comprehensive structure information, especially when the stereochemistry of the molecule is taken into account. (58) 5. Liquid chromatography-Fourier Transfer Infrared (LC-FTIR):…”

Section: Capillary Electrophoresis-mass Spectrometry (Ce-ms)mentioning

confidence: 99%

A Review of Stability Indicating Methods and Forced Degradation Studies

Sonawane,

Chavan,

Narkar

et al. 2023

Int. J. Res. Publ. Rev.

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Stability testing of pharmaceutical products is a complex collection of processes requiring significant expense, time consumption, and scientific skill. In order to improve the quality, efficacy, and safety of a pharmaceutical product, stability testing of drug substances and products is an important step in determining the best storage options and recommending labeling guidelines. The forced degradation parameter performed under stability testing is Hydrolytic degradation, Oxidation degradation, Acidic degradation, Alkaline degradation, and Thermal degradation. In this paper, we present a comprehensive review of the current state of the art of Conventional Techniques and Hyphenated Techniques in the analysis of drug degradation products. We also provide an overview of recent advances in high-performance liquid chromatography (HPLC) and Method development of pharmaceutical drugs.

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Acid Hydrolytic Degradation Profiling of Ezetimibe: Identification, Isolation, and Structural Elucidation of Its Degradants

Modini,

Ranga,

Konidala

et al. 2024

Separation Science Plus

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Ezetimibe (EZE) is a dyslipidemic agent used to treat hyperlipidemia along with statins and diet changes. To ascertain the drug's degradation profile, stress tests were conducted on it in accordance with International Council for Harmonization recommendations. An ultrahigh‐performance liquid chromatography–mass spectrometry method was developed and validated for the identification and quantification of EZE and its degradants. Using preparative high‐performance liquid chromatography, all impurities were isolated, and their structures were characterized thoroughly using advanced spectral techniques. The drug was relatively stable in basic, peroxide, photolytic, and thermal conditions; however, five degradants were observed in acid degradation. Among the five degradants, three degradation products eluted as Peak‐1, Peak‐2, and Peak‐3 which were found to be novel impurities that were not reported previously. However, the remaining two impurities were identified as Peak‐4 and Peak‐5, despite the insufficient information available. The present study has focused on the isolation of these five acid degradation products and the structural confirmation of these degradants by highly efficient spectral techniques. Moreover, the possible degradation mechanism of the azetidinone ring in the presence of acid has been explained, which might be helpful in determining the quality and purity of EZE and similar pharmaceutical compounds.

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Identification, Isolation, and Structural Characterization of Novel Forced Degradation Products of Darunavir Using Advanced Analytical Techniques Like UPLC–MS, Prep-HPLC, HRMS, NMR, and FT-IR Spectroscopy

Cited by 6 publications

References 11 publications

Forced degradation and stability assessment of Tenofovir alafenamide

Forced degradation and stability assessment of Tenofovir alafenamide

A Review of Stability Indicating Methods and Forced Degradation Studies

Acid Hydrolytic Degradation Profiling of Ezetimibe: Identification, Isolation, and Structural Elucidation of Its Degradants

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