Background: Bronchial asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic diseases. Roflumilast is a novel, potent, selective, and long-acting phosphodiesterase 4 (PDE-4) inhibitor for the treatment of bronchial asthma and COPD. It has anti-inflammatory effects, and it has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. Although there have been some other analytical methodologies reported for the determination of roflumilast in pharmaceutical dosage forms, there has not yet been any electrochemical methodology proposed for determination of this unique active pharmaceutical ingredient in its dosage forms.

Objective: The aim of this study was to develop an easily applied, selective, sensitive, accurate, and precise square-wave stripping voltammetric (SWSV) method for the determination of roflumilast in its pharmaceutical dosage forms. In addition, the electrochemical behavior of roflumilast was investigated.

Methods: The proposed method was based on electrochemical reduction of roflumilast at a hanging mercury drop electrode (HMDE) in 0.1 M K2HPO4 and 0.1 M Na2B4O7 (1:1, v/v) buffer at pH 5.0. Two reduction peaks were observed at -1150 mV and -1260 mV with 30 s of accumulation time and -850 mV of accumulation potential time versus Ag/AgCl reference electrode.

Results: The highest peak current values with the best peak definition were observed at a frequency of 50 Hz, scan increment of 5 mV, and pulse amplitude 25 mV. The proposed method was validated by evaluating validation parameters such as linearity, sensitivity, repeatability, accuracy, precision, selectivity, recovery, robustness, and ruggedness. A good linear correlation (r=0.9948) was obtained between the electrochemical response of roflumilast and its concentration in the range of 0.74-3.05 μg mL-1 under the optimum conditions. The obtained accuracy results were between 2.04% and -2.04% while the relative standard deviation of the results was at least 2.78% for intraday and inter-day studies. The mean recovery for the real applications was 100.63% ± 0.52. The electrochemical behavior of roflumilast was investigated by cyclic voltammetry. The cyclic voltammogram of roflumilast exhibited two peaks and the reduction reaction was reversible.

Conclusion: This developed and validated SWSV method was applied successfully for the determination of roflumilast in tablet dosage form (Daxas®) to assess active roflumilast content. Since high- -performance liquid chromatography is a dominant technique in industry for quality control of active pharmaceutical ingredients, the finding in the present study demonstrated that square-wave stripping voltammetry could be easily utilized in routine applications to determine roflumilast content in its dosage forms.

背景：支气管哮喘和慢性阻塞性肺疾病（COPD）是最常见的慢性疾病。Roflumilast 是一种新型、有效、选择性和长效的磷酸二酯酶 4 (PDE-4) 抑制剂，用于治疗支气管哮喘和 COPD。它具有抗炎作用，并且已被证明可以减少 COPD 患者的恶化并改善肺功能。尽管已经报道了一些其他分析方法来测定药物剂型中的罗氟司特，但尚未提出任何电化学方法来测定其剂型中的这种独特的活性药物成分。

目的：本研究的目的是开发一种易于应用、选择性、灵敏、准确和精密的方波溶出伏安法 (SWSV)，用于测定药物剂型中的罗氟司特。此外，研究了罗氟司特的电化学行为。

方法：所提出的方法基于 roflumilast 在悬汞滴电极 (HMDE) 上在 0.1 M K2HPO4 和 0.1 M Na2B4O7 (1:1, v/v) 缓冲液（pH 5.0）中的电化学还原。与 Ag/AgCl 参比电极相比，在 -1150 mV 和 -1260 mV 处观察到两个还原峰，累积时间为 30 秒，累积电位时间为 -850 mV。

结果：在 50 Hz 的频率、5 mV 的扫描增量和 25 mV 的脉冲幅度下观察到具有最佳峰值清晰度的最高峰值电流值。通过评估线性、灵敏度、重复性、准确度、精密度、选择性、回收率、稳健性和耐用性等验证参数来验证所提出的方法。在最佳条件下，罗氟司特的电化学响应与其在 0.74-3.05 μg mL-1 范围内的浓度之间获得了良好的线性相关性（r=0.9948）。获得的准确度结果介于 2.04% 和 -2.04% 之间，而日内和日间研究的结果相对标准偏差至少为 2.78%。实际应用的平均回收率为 100.63% ± 0.52。通过循环伏安法研究了罗氟司特的电化学行为。

结论：这种开发和验证的 SWSV 方法已成功应用于测定片剂剂型 (Daxas®) 中的罗氟司特，以评估活性罗氟司特的含量。由于高效液相色谱是工业中用于活性药物成分质量控制的主要技术，本研究中的发现表明方波溶出伏安法可轻松用于常规应用以确定其剂型中的罗氟司特含量。