A mechanistic explanation on degradation behavior of flibanserin for identification and characterization of its potential degradants using LC-DAD/ESI/APCI-Q-TOF-MS/MS

Sharma, Manish Kumar; Pandey, Komal; Shah, Ravi P.; Kumar, Dinesh; Sengupta, Pinaki

doi:10.1016/j.microc.2021.106281

Cited by 12 publications

(6 citation statements)

References 21 publications

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“…These studies provide information on the type of formulation, container closure system, required storage conditions, and shelf life based on the stability studies. These factors ensure the quality, safety, and efficacy of the drug substance and drug product (Bhagyashree et al, 2015; Kamal et al, 2020; Sharma et al, 2021; Swain et al, 2020; Wadhwa et al, 2021). The drug substance can degrade during storage, shipment, and even manufacturing (Ammann, 2011; Blessy et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Differential role of potential stressors, underlying degradation mechanism, characterization of degradants using LC–MS/MS, and establishment of a stability‐indicating analytical method for duvelisib

Tapkir,

Sahu,

Rajput

et al. 2023

Biomedical Chromatography

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Duvelisib (DUV) was first approved globally in 2018. An extensive literature search revealed that the differential role of a potential degradation medium in altering the shelf‐life of DUV due to its exposure during storage has not been identified till date. Moreover, its degradation impurities and degradation mechanism are not known. In addition, no analytical method has been reported for the quantification of DUV in the presence of its degradation impurities. Therefore, the aim of this study was to identify the impact of different potential degradation media on the stability of DUV, establish the degradation mechanism, and identify its major degradation impurities. The aim was also to establish a stability‐indicating analytical method for the quantification of DUV in the presence of its degradation impurities. This study is the first to report the structure of degradation impurities and the step‐by‐step degradation mechanism of DUV. This information will be useful for the scientific community and manufacturers in optimizing the formulation parameters and/or storage conditions. The validated method can be employed for analysis of stability study and routine quality control samples of newer DUV formulations in pharmaceutical industries. The identified impurities may serve as impurity standards for specifying their limits in the drug after required qualification studies.

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Section: Introductionmentioning

confidence: 99%

Differential role of potential stressors, underlying degradation mechanism, characterization of degradants using LC–MS/MS, and establishment of a stability‐indicating analytical method for duvelisib

Tapkir,

Sahu,

Rajput

et al. 2023

Biomedical Chromatography

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“…Degradation of a pharmaceutical product includes a variety of chemical reactions initiated by different factors including pH, temperature, and light. It is important to study the kinetic behavior of these reactions to generate predictive data for the calculation of shelf life of pharmaceutical products (Pokar et al 2020b;Sahu et al 2021;Sharma et al 2021). The term degradation kinetic refers to the study of the rate of drug degradation.…”

Section: Introductionmentioning

confidence: 99%

Systematic strategies for degradation kinetic study of pharmaceuticals: an issue of utmost importance concerning current stability analysis practices

et al. 2022

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Degradation kinetic study ascertains the shelf life of drugs under different environmental conditions. It can facilitate the prediction of specific critical factors that can affect the quality of pharmaceuticals during storage. To date, general systematic strategies for performing degradation kinetics of drugs have not been discussed in any literature. Moreover, no regulatory guideline is available on the degradation kinetic study of pharmaceuticals. Owing to this, the kinetic behavior of drugs is not being analyzed uniformly. This article provides a detailed insight into degradation kinetic approaches including criticality in selecting different variables for the study. Factors that can affect the quality of degradation kinetic study data have been critically discussed. In addition, a systematic strategy to perform degradation kinetic study with advanced degradation models has been discussed. This article will be helpful for the researcher working in the field of stability analysis and guide to select a logical path for determining the kinetic behavior of drugs. High-quality degradation kinetic data through the properly designed study will help to establish accurate storage conditions of pharmaceuticals. This article is unique and novel of its kind and would have a significant contribution to the field of stability analysis.

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“…Different environmental conditions such as light, humidity, oxygen and temperature may cause the degradation of active ingredients during long‐term storage. A suitable analytical method is required for the separation and analysis of such degradants during stability studies of any drug products containing CMT 12–15 . Although in literature bioanalytical methods for quantification of CMT in biological matrices have been reported, there is no stability‐indicating method available to quantify CMT in the presence of its degradation products 15–19 .…”

Section: Introductionmentioning

confidence: 99%

“…A suitable analytical method is required for the separation and analysis of such degradants during stability studies of any drug products containing CMT. [12][13][14][15] Although in literature bioanalytical methods for quantification of CMT in biological matrices have been reported, there is no stabilityindicating method available to quantify CMT in the presence of its degradation products. [15][16][17][18][19] Furthermore, no data are available on any degradation product of CMT.…”

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confidence: 99%

Mechanism of capmatinib degradation in stress conditions including degradation product characterization using ultra‐high‐performance liquid chromatography‐quadrupole‐time of flight mass spectrometry and stability‐indicating analytical method development

Bhangare

Rajput

Jadav

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale Capmatinib (CMT) has been recently approved for the treatment of non‐small cell lung cancer by the United States Food and Drug Administration (USFDA). Till date, the degradation mechanism of CMT in different stress conditions is not known. Moreover, degradation products (DPs) of the drug are yet to be identified. Characterization study on degradation products of CMT has not been reported before. Furthermore, no previously reported literature is available on the stability‐indicating method of CMT. Methods Owing to the lack of such scientific reports, we developed a sensitive, stability‐indicating method for CMT which can resolve it from all its degradation products. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH Q2 [R1]) guideline. We studied and established the degradation mechanism of CMT in different stress conditions. One degradation product (DP2) was isolated and characterized using 1H NMR. Results The degradation products (DP1, DP2 and DP3) of the drug have been identified and characterized for the first time by using high‐resolution mass spectrometry and 1H NMR spectroscopy. CMT was found to become degraded under acidic, basic and photolytic stress conditions in the solution phase to yield three major DPs. The drug was found to be stable in neutral hydrolysis, oxidation and thermal stress conditions. Conclusions DP1 was formed under acidic and basic hydrolytic conditions, whereas DP2 and DP3 were formed under photolytic conditions. Characterization of all the DPs has been carried out to establish their structures and understand the molecular mechanism behind the degradation of the drug. Few studies reported quantitative analysis of CMT and its metabolites in biological fluids. However, this is the first study to identify the unknown DPs of CMT and the mechanism of its degradation. Moreover, this article reports a stability‐indicating analytical method for CMT which has not yet been reported in any literature.

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A mechanistic explanation on degradation behavior of flibanserin for identification and characterization of its potential degradants using LC-DAD/ESI/APCI-Q-TOF-MS/MS

Cited by 12 publications

References 21 publications

Differential role of potential stressors, underlying degradation mechanism, characterization of degradants using LC–MS/MS, and establishment of a stability‐indicating analytical method for duvelisib

Differential role of potential stressors, underlying degradation mechanism, characterization of degradants using LC–MS/MS, and establishment of a stability‐indicating analytical method for duvelisib

Systematic strategies for degradation kinetic study of pharmaceuticals: an issue of utmost importance concerning current stability analysis practices

Mechanism of capmatinib degradation in stress conditions including degradation product characterization using ultra‐high‐performance liquid chromatography‐quadrupole‐time of flight mass spectrometry and stability‐indicating analytical method development

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