Influence of Peroxide Impurities in Povidone on the Stability of Selected β-Blockers with the Help of HPLC

Prachi, Saklecha; Chaudhary, Komal; Priti, Mehta J.

doi:10.1208/s12249-017-0716-2

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…Prachi et al 25 investigated the compatibility of several ingredients, including labetalol, atenolol, propanol hydrochloride, hydrochloride, bisoprolol fumarate, metoprolol succinate, and carvedilol with the povidone. Peroxide from povidone could affect the stability of selected β-blockers where the degradation was due to peroxides that exist as an impurity in povidone.…”

Section: Forced Degradationmentioning

confidence: 99%

Forced Degradation of Flibanserin Bulk Drug: Development and Validation of Stability Indicating RP-HPLC Method

Chew¹,

Lee²,

Khor³

et al. 2022

IJPER

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Background: Flibanserin had been approved as the first drug by United State Food and Drug Administration (USFDA) for the treatment of female sexual interest/arousal disorder of any severity. However, the stability of this drug has yet to be studied extensively. Objectives:The objectives of this study were to optimize the stability indicating method and evaluate the stability of flibanserin under various forced degradation conditions, determine the order of the degradation kinetics, half-life and shelf life of flibanserin under certain stress conditions. The stability of flibanserin under various stress conditions which would reflect the important aspects of storage condition and excipients which should be avoided in the formulation of this drug substance into final drug products. Methods: Stability indicating method was developed using HPLC. It was validated according to ICH guideline for its linearity, precision, accuracy, robustness, LOD and LOQ. The forced degradation was performed under various stress conditions, namely acidic, alkaline and oxidative conditions (H 2 O 2 , AIBN and FeCl 3 ). LC-MS was utilised for identification of the degradation impurities, and the degradation kinetics was evaluated based on the kinetic models. Results: Degradation of flibanserin was noticed under oxidative conditions. Flibanserin was degraded under H 2 O 2 oxidation at room temperature, while AIBN and FeCl 3 at elevated temperature. Two N-oxide impurities were identified under H 2 O 2 oxidation. Flibanserin was degraded following the first-order kinetic under H 2 O 2 and AIBN oxidation, while zero-order under FeCl 3 oxidation. Half-life and shelf life of flibanserin under respective stress conditions were determined. Conclusion: It is concluded that the RP-HPLC method developed could be used as the stability indicating method in determination of flibanserin stability and its impurities. Flibanserin is sensitive towards oxidative degradation. The impurities and the order of the degradation kinetics were identified.

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Section: Forced Degradationmentioning

confidence: 99%

Forced Degradation of Flibanserin Bulk Drug: Development and Validation of Stability Indicating RP-HPLC Method

Chew¹,

Lee²,

Khor³

et al. 2022

IJPER

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“…We used atenolol (Bogaert, Rosseel, & Lefebvre, 1984;Prachi, Komal, & Priti, 2017), ICI 118,551 (Baker, 2010;Propping, Newe, Kaumann, Wirth, & Ravens, 2015) and propranolol (Hoffmann, Leitz, Oberdorf-Maass, Lohse, & Klotz, 2004;Tan & Yang, 2016;Zhang et al, 2011b) as the selective β 1 -AR, selective β 2 -AR and non-selective β-AR antagonists, respectively. The doses of the β-AR antagonists were selected according to our previous experimental data, which were shown to be the optimal doses for stable monitoring of haemodynamics (Zhang et al, 2011a(Zhang et al, , 2012.…”

Section: Changes In Haemodynamic Indexesmentioning

confidence: 99%

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

Zhang

Cao

et al. 2020

Experimental Physiology

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New Findings What is the central question of this study?The acute hypoxic compensatory reaction is based on haemodynamic changes, and β‐adrenoceptors are involved in haemodynamic regulation. What is the role of β‐adrenoceptors in haemodynamics during hypoxic exposure? What is the main finding and its importance?Activation of β2‐adrenoceptors attenuates the increase in pulmonary artery pressure during hypoxic exposure. This compensatory reaction activated by β2‐adrenoceptors during hypoxic stress is very important to maintain the activities of normal life. Abstract The acute hypoxic compensatory reaction is accompanied by haemodynamic changes. We monitored the haemodynamic changes in rats undergoing acute hypoxic stress and applied antagonists of β‐adrenoceptor (β‐ARs) subtypes to reveal the regulatory role of β‐ARs on haemodynamics. Sprague–Dawley rats were randomly divided into control, atenolol (β1‐AR antagonist), ICI 118,551 (β2‐AR antagonist) and propranolol (non‐selective β‐AR antagonist) groups. Rats were continuously recorded for changes in haemodynamic indexes for 10 min after administration. Then, a hypoxic ventilation experiment [15% O2, 2200 m a.sl., 582 mmHg (0.765 Pa), PnormalO2 87.3 mmHg; Xining, China] was conducted, and the indexes were monitored for 5 min after induction of hypoxia. Plasma catecholamine concentrations were also measured. We found that, during normoxia, the mean arterial pressure, heart rate, ascending aortic blood flow and pulmonary artery pressure were reduced in the propranolol and atenolol groups. Catecholamine concentrations were increased significantly in the atenolol group compared with the control group. During hypoxia, mean arterial pressure and total peripheral resistance were decreased in the control, propranolol and ICI 118,551 groups. Pulmonary arterial pressure and pulmonary vascular resistance were increased in the propranolol and ICI 118,551 groups. During hypoxia, catecholamine concentrations were increased significantly in the control group, but decreased in β‐AR antagonist groups. In conclusion, the β2‐AR is involved in regulation of pulmonary haemodynamics in the acute hypoxic compensatory reaction, and the activation of β2‐ARs attenuates the increase in pulmonary arterial pressure during hypoxic stress. This compensatory reaction activated by β2‐ARs during hypoxic stress is very important to maintain activities of normal life.

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“…Some specific functional groups in API may be susceptible to degradation mechanisms, i.e., hydrolysis, oxidation, polymerization, etc. [4][5][6][12][13][14].…”

Section: Classification Of Impuritiesmentioning

confidence: 99%

Determination of Impurities in Pharmaceuticals: Why and How?

Liu¹,

Chen²

2019

Quality Management and Quality Control - New Trends and Developments

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The presence of impurities, particularly the API-related impurities, i.e., degradation-related impurities (DRIs) and interaction-related impurities (IRIs), may affect the quality, safety, and efficacy of drug products. Since the regulatory requirements and management strategies are required to be established and complied, sources of impurities shall be carefully classified prior to take subsequent steps such as development of analytical methods and acceptance criteria. Current international regulatory requirements for the management of impurities in pharmaceuticals were reviewed. Procedures for the identification of DPIs in pharmaceuticals, i.e., ethyl cysteinate dimer, (R)-N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine, sestamibi, etc., using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were studied. Scheme for the establishment of analytical methods and acceptance criteria of process-related impurities (PRIs) and DRIs in accordance with the requirements of International Council for Harmonization (ICH) and algorithm to perform the identification of DPIs by using LC-MS/MS has been proposed. Practice of kinetic study to distinguish PRIs and DRIs, determination of the potential core fragments coupled with a predicted list of relevant transformations for conducting MS/MS scans, applications of stable isotope distribution patterns or natural abundances, practice of mass balance, etc., have been well demonstrated to justify the reliabilities of identification results.

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Influence of Peroxide Impurities in Povidone on the Stability of Selected β-Blockers with the Help of HPLC

Cited by 8 publications

References 15 publications

Forced Degradation of Flibanserin Bulk Drug: Development and Validation of Stability Indicating RP-HPLC Method

Forced Degradation of Flibanserin Bulk Drug: Development and Validation of Stability Indicating RP-HPLC Method

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

Determination of Impurities in Pharmaceuticals: Why and How?

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