高效液相色谱-DAD-ESI-IT-TOF-MSn表征弗利班塞林新降解产物的不同视角及其药物配方分析的实验室间比较。

IF 1.7 4区 农林科学 Q3 CHEMISTRY, ANALYTICAL
Aysun Geven, Saniye Özcan, Serkan Levent, Nafiz Öncü Can
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引用次数: 0

摘要

背景:Flibanserin(FLB)是最早合成的抗抑郁药物;然而,由于其对性活动的增强作用,它于2015年被批准用于治疗女性性欲低下障碍。目的:本研究的目的是开发一种新的、经过充分验证的HPLC方法,用于分析药物制剂中FLB及其降解产物,并使用HPLC-DAD-ESI-IT-TOF-MSn鉴定可能的形成机制。方法:在Supelco Ascentis®Express系列苯基己基柱(100 × 4.6 mm,内径2.7 µm)。流动相为乙腈-乙酸铵溶液(50:50,v/v,10 mM,pH 5.4)混合物,其以0.5的速率泵送 毫升/分钟。结果:1-(2-(4-(3-羟基-5-(三氟甲基)苯基)哌嗪-1-基)乙基)-1,3-二氢-2H-苯并[d]咪唑-2-酮是一种新的降解产物,质量为407.1695,分子式为C20H21F3N4O2,误差约0.001 ppm。所开发的方法适用于2.5-50.0范围内98%的准确度 µg/mL范围。LOD和LOQ约为500 ng/mL和1.50 µg/mL。实验室之间的可转移性和变异性通过实验室间比较进行测试,并通过单向方差分析进行评估。结论:首次观察并鉴定了一种在氧化强制降解条件下产生的新型FLB降解产物;此外,还研究了除FLB分解外降解产物的形成动力学。此外,还进行了实验室间比较,并使用两种仪器配置对拟Addyi®(Sprout Pharmaceuticals,股份有限公司)样品的拟议方法应用进行了测试。亮点:根据国际协调理事会(Q2)R1,开发并充分验证了一种新的稳定性指示测定方法,用于分析药物制剂中的FLB。在氧化强制降解条件下鉴定了一种新的降解产物,并用HPLC-DAD-ESI-IT-TOF-MS3进行了表征。此外,还揭示了降解产物的可能机理和形成动力学。此外,将开发的方法转移到另一台LC-PDA仪器上进行实验室间比较。最后,将当前的方法应用于两种仪器中Addy的伪公式,并应用ANOVA进行评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Different Perspective on the Characterization of a New Degradation Product of Flibanserin With HPLC-DAD-ESI-IT-TOF-MSn and Its Pharmaceutical Formulation Analysis With Inter-Laboratory Comparison.

A Different Perspective on the Characterization of a New Degradation Product of Flibanserin With HPLC-DAD-ESI-IT-TOF-MSn and Its Pharmaceutical Formulation Analysis With Inter-Laboratory Comparison.

A Different Perspective on the Characterization of a New Degradation Product of Flibanserin With HPLC-DAD-ESI-IT-TOF-MSn and Its Pharmaceutical Formulation Analysis With Inter-Laboratory Comparison.

A Different Perspective on the Characterization of a New Degradation Product of Flibanserin With HPLC-DAD-ESI-IT-TOF-MSn and Its Pharmaceutical Formulation Analysis With Inter-Laboratory Comparison.

Background: Flibanserin (FLB) was first synthesized as an antidepressant drug; however, due to its enhancing effects on sexual activity, it was approved for treatment of hypoactive sexual desire disorder in women in 2015.

Objective: The aim of this study was to develop a new and fully validated HPLC method for analysis of FLB in pharmaceutical formulations besides its degradation products, and identification of possible formation mechanisms by using HPLC-DAD-ESI-IT-TOF-MSn.

Method: The HPLC separation was achieved in a Supelco Ascentis® Express series phenyl hexyl column (100 × 4.6 mm, ID 2.7 µm). The mobile phase was acetonitrile-ammonium acetate solution (50:50, v/v, 10 mM, pH 5.4) mixture, which was pumped at the rate of 0.5 mL/min. Chromatography, detection, and structural identification was performed by using a LCMS-IT-TOF instrument (Shimadzu, Japan).

Results: 1-(2-(4-(3-hydroxy-5-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one is proposed as a novel degradation product, with a mass of 407.1695 and a formula of C20H21F3N4O2 with a margin of error about 0.001 ppm. The developed method is applicable with 98% accuracy within the 2.5-50.0 µg/mL range. The LOD and LOQ were about 500 ng/mL and 1.50 µg/mL, respectively. The transferability and variation between laboratories were tested by inter-laboratory comparison and evaluated with one-way analysis of variance.

Conclusions: A novel FLB degradation product, which was produced under oxidative forced degradation conditions was observed and identified for the first time; in addition, the formation kinetics of the degradation product besides decomposition of FLB was studied. Furthermore, an inter-laboratory comparison was carried out, and application of the proposed method on a pseudo Addyi® (Sprout Pharmaceuticals, Inc.) sample was tested using both instrument configurations.

Highlights: A novel stability-indicating assay method was developed and fully validated according to the International Council on Harmonization (Q2) R1 for the analysis of FLB in the pharmaceutical preparations. A new degradation product was identified in the oxidative forced degradation condition and characterized using HPLC-DAD-ESI-IT-TOF-MS3. Moreover, the possible mechanism and the formation kinetic of the degradation product were revealed. In addition, the developed method was transferred to another LC-PDA instrument for inter-laboratory comparison. Finally, the current method was applied to a pseudo formulation of Addy in both instruments, and ANOVA was applied for evaluation.

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来源期刊
Journal of AOAC International
Journal of AOAC International 医学-分析化学
CiteScore
3.10
自引率
12.50%
发文量
144
审稿时长
2.7 months
期刊介绍: The Journal of AOAC INTERNATIONAL publishes the latest in basic and applied research in analytical sciences related to foods, drugs, agriculture, the environment, and more. The Journal is the method researchers'' forum for exchanging information and keeping informed of new technology and techniques pertinent to regulatory agencies and regulated industries.
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