Synthesis and characterization of oxitropium bromide related substances and novel stability indicating HPLC methods

Atici, Esen Bellur; Ağtaş, Çağan; Yazar, Yücel; Rıdvanoğlu, Nurten

doi:10.1016/j.jpba.2020.113145

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…Comparing tropic acid 3 h with commercial ( R )‐tropic acid as reference, we established that the ( R )‐enantiomer of 2 h was formed upon boracarboxylation of 1 h with ( S , S)‐ QuinoxP. The transformation of ( R )‐ 2 h to ( S )‐tropic acid 3 h also demonstrates the formal total synthesis of the natural product ( S )‐scopolamine, [29] and the anti‐cholineric drugs ( S )‐oxitropium (Oxivent) [30] and ( S )‐tropicamide (Mydriacyl) [31] via a boracarboxylation (Scheme 4).…”

Section: Resultsmentioning

confidence: 77%

Asymmetric Boracarboxylation of Styrenes Using Carbon Dioxide

Pettersen,

Dat Do,

Gorantla

et al. 2024

Adv Synth Catal

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The boracarboxylation reaction has potential for production of natural products and drug candidates, but the development of an asymmetric version of this transformation is challenging. We report an enantioselective boracarboxylation of styrenes, enabled by a copper catalyst containing chiral phosphines. Our experimental conditions provide yields between 31‐76% and enantiomeric ratios from 80:20 up to 98:2 for electron‐rich styrenes. Oxidation of a boracarboxylation product provide (S)‐tropic acid, an intermediate towards several tropane alkaloids. A computational analysis of the mechanistic details shows a complex pattern of competing reaction pathways, explaining challenges encountered when developing asymmetric reactions using CO2.

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Section: Resultsmentioning

confidence: 77%

Asymmetric Boracarboxylation of Styrenes Using Carbon Dioxide

Pettersen,

Dat Do,

Gorantla

et al. 2024

Adv Synth Catal

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“…Stress testing efforts can be used to gauge the intrinsic stability of a given drug based on the establishment of the associated degradation pathways, thereby enabling the identification of likely degradation products [23]. These findings can inform manufacturing processes, drug storage, and the determination of an appropriate expiration date.…”

Section: Forced Degradation and Long-term Storage Analysesmentioning

confidence: 99%

HPLC and LC–MS/MS-Based Quantitative Characterization of Related Substances Associated with Sotalol Hydrochloride

Zhu,

Shen,

Wang

et al. 2024

Molecules

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In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography (HPLC) protocol. Further characterization of these substances was then performed via liquid chromatography–mass spectroscopy (LC–MS/MS) and nuclear magnetic resonance (NMR) approaches. For these analyses, commercial STHCl samples were used for quantitative HPLC studies and the degradation of STHCl under acidic (1M HCl), alkaline (1M NaOH), oxidative (30% H2O2), photolytic (4500 Lx), and thermal stress conditions (100 °C) was assessed. This approach revealed this drug to be resistant to acidic, alkaline, and high-temperature conditions, whereas it was susceptible to light and oxidation as confirmed through long-term experiments. The putative mechanisms governing RS formation were also explored, revealing that RS3 was derived from the manufacturing process, whereas RS2 was generated via oxidation and RS1 was generated in response to light exposure. The cytotoxicity of these RS compounds was then assessed using MTT assays and acute toxicity test. Overall, this study provides details regarding the characterization, isolation, quantification, and toxicological evaluation of STHCl and associated RS compounds together with details regarding the precise, specific, and reliable novel HPLC technique, thus providing the requisite information necessary to ensure STHCl purity and safety.

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