Pharmacokinetic Analysis of Gatifloxacin and Dexamethasone in Rabbit Ocular Biofluid Using a Sensitive and Selective LC–MS/MS Method

IF 1.9 3区 化学 Q3 BIOCHEMICAL RESEARCH METHODS
Arpon Biswas, Abhijit Deb Choudhury, Anjali Mishra, Sarvesh Kumar Verma, Amol Chhatrapati Bisen, Sachin Nashik Sanap, Sristi Agrawal, Mukesh Kumar, Shivansh Kumar, Rabi Sankar Bhatta
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引用次数: 0

Abstract

Bacterial keratitis (BK) is an infection that causes inflammation of the cornea and, if severe, can result in blindness. Topical fluoroquinolones combined with corticosteroids have been shown to be useful in the treatment of BK. A rapid, selective, and sensitive bioanalytical method for simultaneous quantification of Gatifloxacin (GAT) and Dexamethasone (DEX) has been developed and validated using tandem mass spectrometry (LC–MS/MS). Optimal separation was accomplished in under 5 min using an Agilent Zorbax C18 column (100 mm × 4.6 mm, 3.5 μm). The mobile phase was composed of a blend of 0.2% formic acid in triple distilled water and methanol with a flow rate of 0.65 mL/min in isocratic mode. GAT and DEX were detected in positive electrospray ionization multiple reaction monitoring mode (MRM), and the retention time was found to be at 1.64 and 2.93 min, respectively. The linearity of GAT and DEX was found to be in the range of 1.56–400 ng mL−1 with good precision and accuracy. The method was validated according to USFDA regulatory guidelines. The validated method was effectively utilized for preclinical pharmacokinetic analysis of GAT and DEX in rabbit tear fluid following the topical application of a commercial formulation.

利用灵敏且具有选择性的 LC-MS/MS 方法对兔眼部生物流体中的加替沙星和地塞米松进行药代动力学分析
细菌性角膜炎(BK)是一种引起角膜炎症的感染,严重时可导致失明。外用氟喹诺酮类药物联合皮质类固醇已被证明可用于治疗 BK。利用串联质谱法(LC-MS/MS)开发并验证了一种快速、选择性强且灵敏的生物分析方法,用于同时定量检测加替沙星(GAT)和地塞米松(DEX)。使用 Agilent Zorbax C18 色谱柱(100 mm × 4.6 mm,3.5 μm)在 5 分钟内完成最佳分离。流动相为 0.2% 甲酸混合三蒸馏水和甲醇,流速为 0.65 mL/min,采用等度模式。GAT和DEX在正离子电喷雾多反应监测模式(MRM)下检测,保留时间分别为1.64和2.93 min。GAT和DEX的线性范围为1.56-400 ng mL-1,具有良好的精密度和准确度。该方法根据美国食品及药物管理局(USFDA)的法规指南进行了验证。该方法有效地用于兔泪液中GAT和DEX的临床前药代动力学分析。
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来源期刊
Journal of Mass Spectrometry
Journal of Mass Spectrometry 化学-光谱学
CiteScore
5.10
自引率
0.00%
发文量
84
审稿时长
1.5 months
期刊介绍: The Journal of Mass Spectrometry publishes papers on a broad range of topics of interest to scientists working in both fundamental and applied areas involving the study of gaseous ions. The aim of JMS is to serve the scientific community with information provided and arranged to help senior investigators to better stay abreast of new discoveries and studies in their own field, to make them aware of events and developments in associated fields, and to provide students and newcomers the basic tools with which to learn fundamental and applied aspects of mass spectrometry.
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