Abstract：
Determining a drug\'s bioavailability and bioequivalence is important for developing and approving a drug product. The procedure supports applications for generic drug products and novel therapeutic substances, makes important decisions regarding safety and efficacy, and measures a drug\'s concentration in biological matrices. This study aimed to develop and validate a specific, simple, sensitive, and accurate method using liquid chromatography-tandem mass spectrometry (LC-MS) for measuring bumetanide (BUM) in human plasma. Chromatographic separation was achieved using a Hypurity C18 column (4.6 × 50 mm, 5 μm) under isocratic conditions, and LC-MS detected positive ionization acquisition modes. Protonated precursor to product ion transitions were observed at m/z 365.08 → 240.10 and 370.04 → 244.52 for BUM and internal standard, respectively. The linear range of BUM in plasma samples was 3.490-401.192 ng/mL. The inter-precision value ranged from 1.76% to 4.75%. The inter-accuracy value ranged from 96.46% to 99.95%. The method was adequately validated per the U.S. Food and Drug Administration guidelines, and the results were within permissible bounds. The Cmax and Tmax values were ~53.097 ± 13.537 ng/mL and 1.25 (0.67-5.00) h, respectively. The new approach showed satisfactory results for studying BUM in human plasma with potential use in pharmacokinetic and bioequivalence investigations.
摘要：
确定药物的生物利用度和生物等效性对于开发和批准药物产品很重要。该程序支持仿制药产品和新型治疗物质的应用，做出关于安全性和有效性的重要决定，并测量药物在生物基质中的浓度。本研究旨在开发和验证一种特定的，简单,敏感,使用液相色谱-串联质谱（LC-MS）测量人血浆中布美坦（BUM）的准确方法。使用HypurityC18柱(4.6×50mm，5μm)在等度条件下，和LC-MS检测到正离子化采集模式。对于BUM和内标，在m/z365.08→240.10和370.04→244.52处观察到质子化前体到产物离子的跃迁，分别。BUM在血浆样品中的线性范围为3.490-401.192ng/mL。精度间值在1.76%至4.75%的范围内。间精度值范围为96.46%至99.95%。该方法已根据美国食品和药物管理局指南进行了充分验证，结果在允许范围内。Cmax和Tmax值分别为~53.097±13.537ng/mL和1.25(0.67-5.00)h,分别。新方法在研究人血浆中的BUM方面显示出令人满意的结果，可用于药代动力学和生物等效性研究。
