Development and validation of a rapid chromatographic method for the analysis of flunarizine and its main production impurities

O'Connor, Niamh; Geary, Michael; Wharton, Mary; Sweetman, Paul

doi:10.1016/j.jpha.2012.12.005

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…Overdose can have a detrimental impact on breathing and can cause swelling of the throat or tongue. ,, Hence, the determination of antihistamine drugs in blood is of immense importance. To this end, high-performance liquid chromatography (HPLC) is frequently used, most often in combination with spectrophotometric detectors − or coupled to mass spectrometry (HPLC–MS). , In this work, we investigate the possibility of applying a nanomaterial-based electrochemical detector (HPLC-ECD) offering enhanced sensitivity compared to both MS and spectrophotometry.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical HPLC Determination of Piperazine Antihistamine Drugs Employing a Spark-Generated Nickel Oxide Nanoparticle-Modified Carbon Fiber Microelectrode

Belbasi,

Petr,

Sevcik

et al. 2024

ACS Omega

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In this work, we demonstrate a sensitive highperformance liquid chromatography (HPLC) method for the determination of piperazine antihistamine drugs employing innovative electrochemical detection based on a spark-generated nickel oxide nanoparticle-modified carbon fiber microelectrode built into a miniaturized electrochemical detector. The direct carbon fiber-tonickel plate electrode spark discharge, carried at 0.8 kV DC, with the nickel electrode connected to the negative pole of the high-voltage power supply, provides extremely fast (1 s) in situ tailoring of the carbon fiber microelectrode surface by nickel oxide nanoparticles. It has been found that nickel oxide nanoparticles exhibit an electrocatalytic effect toward the piperazine moiety electrooxidation process, as confirmed by voltammetric experiments, revealing the shift in the peak potential from 1.25 to 1.09 V versus Ag/AgCl. Cetirizine, cyclizine, chlorcyclizine, flunarizine, meclizine, and buclizine were selected as sample piperazine antihistamine drugs, while diclofenac served as an internal standard. The isocratic reversed-phase separation of the above set was achieved within 15 min using an ARION-CN 3 μm column with a binary mobile phase consisting of 50 mM phosphate buffer (pH 3) and methanol (45/55, v/v). The limits of detection (LOD) were within the range of 3.8−120 nM (for cyclizine and buclizine) at E = +1500 mV (vs Ag/AgCl), while the response was linear within the concentration range measured up to 5 μmol L −1 . The method was successfully applied to the determination of piperazine antihistamine drugs in spiked plasma samples.

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Section: Introductionmentioning

confidence: 99%

Electrochemical HPLC Determination of Piperazine Antihistamine Drugs Employing a Spark-Generated Nickel Oxide Nanoparticle-Modified Carbon Fiber Microelectrode

Belbasi,

Petr,

Sevcik

et al. 2024

ACS Omega

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Synergistic effect of 1-butyl-2,3-dimethylimidazolium bis (trifluoromethanesulfonyl) imide and titanium oxide on the redox behaviour of flunarizine in solubilized media

Singh

Jadon

Jain

2018

Colloids and Surfaces B: Biointerfaces

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Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear

Thakur,

Rus,

Herbert

et al. 2024

J Nanobiotechnol

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Treatment-induced ototoxicity and accompanying hearing loss are a great concern associated with chemotherapeutic or antibiotic drug regimens. Thus, prophylactic cure or early treatment is desirable by local delivery to the inner ear. In this study, we examined a novel way of intratympanically delivered sustained nanoformulation by using crosslinked hybrid nanoparticle (cHy-NPs) in a thermoresponsive hydrogel i.e. thermogel that can potentially provide a safe and effective treatment towards the treatment-induced or drug-induced ototoxicity. The prophylactic treatment of the ototoxicity can be achieved by using two therapeutic molecules, Flunarizine (FL: T-type calcium channel blocker) and Honokiol (HK: antioxidant) co-encapsulated in the same delivery system. Here we investigated, FL and HK as cytoprotective molecules against cisplatin-induced toxic effects in the House Ear Institute - Organ of Corti 1 (HEI-OC1) cells and in vivo assessments on the neuromast hair cell protection in the zebrafish lateral line. We observed that cytotoxic protective effect can be enhanced by using FL and HK in combination and developing a robust drug delivery formulation. Therefore, FL-and HK-loaded crosslinked hybrid nanoparticles (FL-cHy-NPs and HK-cHy-NPs) were synthesized using a quality-by-design approach (QbD) in which design of experiment-central composite design (DoE-CCD) following the standard least-square model was used for nanoformulation optimization. The physicochemical characterization of FL and HK loaded-NPs suggested the successful synthesis of spherical NPs with polydispersity index < 0.3, drugs encapsulation (> 75%), drugs loading (~ 10%), stability (> 2 months) in the neutral solution, and appropriate cryoprotectant selection. We assessed caspase 3/7 apopototic pathway in vitro that showed significantly reduced signals of caspase 3/7 activation after the FL-cHy-NPs and HK-cHy-NPs (alone or in combination) compared to the CisPt. The final formulation i.e. crosslinked-hybrid-nanoparticle-embedded-in-thermogel was developed by incorporating drug-loaded cHy-NPs in poloxamer-407, poloxamer-188, and carbomer-940-based hydrogel. A combination of artificial intelligence (AI)-based qualitative and quantitative image analysis determined the particle size and distribution throughout the visible segment. The developed formulation was able to release the FL and HK for at least a month. Overall, a highly stable nanoformulation was successfully developed for combating treatment-induced or drug-induced ototoxicity via local administration to the inner ear. Graphical Abstract

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Development and validation of a rapid chromatographic method for the analysis of flunarizine and its main production impurities

Cited by 3 publications

References 11 publications

Electrochemical HPLC Determination of Piperazine Antihistamine Drugs Employing a Spark-Generated Nickel Oxide Nanoparticle-Modified Carbon Fiber Microelectrode

Electrochemical HPLC Determination of Piperazine Antihistamine Drugs Employing a Spark-Generated Nickel Oxide Nanoparticle-Modified Carbon Fiber Microelectrode

Synergistic effect of 1-butyl-2,3-dimethylimidazolium bis (trifluoromethanesulfonyl) imide and titanium oxide on the redox behaviour of flunarizine in solubilized media

Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear

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