Isolation and identification of forced degradation products of Febuxostat

Encequidar mesylate salt is a novel, little‐absorbed P‐glycoprotein (P‐gp) that facilitates oral absorption. It is a substance that stops the P‐gp adenosine triphosphate‐binding cassette transporter from working. To ascertain the drug substance's inherent stability, it underwent stress testing under a variety of degradation conditions, including acidic hydrolysis, alkaline hydrolysis, oxidative, thermal, and photolytic, in accordance with regulatory requirements. It was discovered that the drug substance is highly unstable in alkaline conditions, and the degradation leads to the formation of two unique, unknown degradation products. Utilizing UHPLC–ESI/MS for identification and mass‐triggered preparative HPLC for isolation, the degradants’ structures were definitively determined by using high‐resolution mass spectrometry and 2D NMR methodologies. These unique degradation products were determined to be novel impurities of the encequidar drug substance and were firmly proven to be its hydrolysis components on the basis of spectral and chromatographic data. Possible potential mechanisms have been proposed to explain the formation of the degradants.

Encequidar Mesylate Novel Degradation Products: Isolation, Characterization, and Structural Evaluation Using Mass‐Triggered Preparative HPLC, HRMS, and NMR Techniques

Surukonti,

Manabolu Surya

2024

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

Modini,

Ranga,

Konidala

et al. 2024

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.

Acid Degradation Study of Dapagliflozin: Structural Characterization of Dapagliflozin and its Degradation Products Using Advanced Analytical Techniques and In Silico Toxicity Prediction

Bhuma,

Maddala,

Raghupathi

et al. 2024

The research investigates the stress degradation behavior of Dapagliflozin (DAP), a type‐2 diabetic treatment, following International Council for Harmonization Guidelines. It found that DAP is stable in thermal, photolytic, neutral, and alkaline hydrolysis conditions, but significant degradation was detected in acid hydrolysis. Two novel degradation products (DPs) were identified and isolated in acid degradation, providing the first documented structural characterization of all two DPs. The identification of DPs was achieved through the use of ultra‐high‐performance liquid chromatography–mass spectrometry, semi‐preparative high‐performance liquid chromatography, and nuclear magnetic resonance spectroscopy for structural characterization. In acid degradation, a total of two primary DPs, degradation products 1 and 2 (DP1 and DP2), were found and separated. It was not previously reported that the two DPs that were generated were all new. This is the first time that these two DPs’ full structural characterizations employing cutting‐edge analytical techniques have been recorded. In the current work, liquid chromatography mass spectroscopy and nuclear magnetic resonance spectroscopy were employed to get a specific confirmation of DP structures. In the further, degrading impurity with lower runtime will also be identified using the current method.