Department of Pharmaceutical Analysis, GITAM School of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, India.
Rapid Commun Mass Spectrom. 2024 Feb 15;38(3):e9676. doi: 10.1002/rcm.9676.
Ozenoxacin (OXC) is an antibiotic used topically to treat impetigo. This study aimed to evaluate the degradation products (DP) of OXC drug substance under different stress conditions, including hydrolysis, oxidation, thermal and photolysis, in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines Q1A(R2) and Q1B. The analytical technique was validated in compliance with ICH Q2(R1) requirements.
The drug substance underwent degradation under various forced degradation conditions, including thermal, oxidative, photolytic and hydrolytic (neutral, acidic and basic) degradation. Overall, four DPs were formed under oxidative stress conditions with AIBN. The formed DPs were identified and separated using a Shimadzu LC system with a reversed-phase Phenomenex Kinetex C18 column (4.6 × 250 mm, 5 μm), using 10 mM NH CH COOH buffer (pH -5.0) as mobile phase A and acetonitrile as mobile phase B at a detection wavelength of 254 nm.
The drug was found to be stable in neutral, acidic, basic and oxidative degradation conditions with hydrogen peroxide. Liquid chromatography-electrospray ionisation-quadrupole time-of-flight-tandem mass spectrometry- was employed in positive ionisation mode to analyse both the drug and the mass of the identified DP. The mechanism and the pathway of mass fragmentation have been proposed. The developed method was accurate, repeatable, linear and selective for further research. The ADMET Predictor software was applied to predict the in silico toxicity of the drugs and its DPs as well as their physicochemical characteristics.
奥昔沙星（OXC）是一种外用抗生素，用于治疗脓疱疮。本研究旨在根据国际人用药品注册技术协调会（ICH）指南 Q1A（R2）和 Q1B 评价 OXC 原料药在不同应激条件下（包括水解、氧化、热和光解）的降解产物（DP）。分析技术符合 ICH Q2（R1）要求进行了验证。
药物在各种强制降解条件下（包括热、氧化、光解和水解（中性、酸性和碱性）降解）进行降解。总的来说，在 AIBN 存在的氧化应激条件下形成了四个 DP。使用 Shimadzu LC 系统，采用反相 Phenomenex Kinetex C18 柱（4.6×250mm，5μm），以 10mM NH 4 CH 3 COOH 缓冲液（pH-5.0）为流动相 A，乙腈为流动相 B，在 254nm 检测波长下，分离和鉴定形成的 DP。
在中性、酸性、碱性和氧化降解条件（用过氧化氢）下，药物被发现是稳定的。采用正离子化模式的液相色谱-电喷雾离子化-四极杆飞行时间串联质谱法分析药物及其鉴定 DP 的质量。提出了质量碎裂的机理和途径。所开发的方法准确、可重复、线性且适合进一步研究。ADMET Predictor 软件用于预测药物及其 DP 的体内毒性以及它们的物理化学特性。
