Iqbal Muzaffar, Ezzeldin Essam, Al-Rashood Khalid A, Bajrai Amal A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
J Anal Toxicol. 2015 Mar;39(2):106-12. doi: 10.1093/jat/bku126. Epub 2014 Nov 16.
Vilazodone is a novel antidepressant agent, approved by the US Food and Drug Administration (US FDA) for the treatment of major depressive disorder. In this study, a fast sensitive ultra-high performance liquid chromatography-tandem mass spectroscopy method was developed and validated for the determination of vilazodone in human plasma. After a simple protein precipitation by acetonitrile, both vilazodone and risperidone (internal standard, IS) were separated on an Acquity UPLC BEH™ C18 column (50 × 2.1 mm, 1.7 µm). An isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v) was used at the 0.3 mL/min flow rate. Both vilazodone and IS were eluted at 0.44 and 0.47 min, respectively, having a run time of 1.0 min. Detection and quantification were performed using an electrospray ionization source in positive mode by multiple reaction monitoring. The precursor to product ion transitions were monitored at m/z 442.19 > 154.99 for vilazodone and m/z 411.18 > 191.07 for IS, respectively. The standard curve (0.40-500 ng/mL) was found to be linear with a lower limit of quantification 0.40 ng/mL. All validation results were found to be within acceptable limits as per guidelines for bioanalytical method validation (US FDA and European Medicines Agency). To the best of our knowledge, this is the first fully validated assay for the determination of vilazodone in human plasma and was successfully applied to an oral pharmacokinetic study in rats.
维拉唑酮是一种新型抗抑郁药，已获美国食品药品监督管理局（US FDA）批准用于治疗重度抑郁症。在本研究中，开发并验证了一种快速灵敏的超高效液相色谱 - 串联质谱法，用于测定人血浆中的维拉唑酮。通过乙腈进行简单的蛋白沉淀后，维拉唑酮和利培酮（内标，IS）在Acquity UPLC BEH™ C18柱（50×2.1 mm，1.7 µm）上分离。以乙腈：10 mM醋酸铵（80:20，v/v）作为等度流动相，流速为0.3 mL/min。维拉唑酮和内标分别在0.44分钟和0.47分钟洗脱，运行时间为1.0分钟。采用电喷雾电离源在正模式下通过多反应监测进行检测和定量。分别监测维拉唑酮的m/z为442.19 > 154.99和内标的m/z为411.18 > 191.07的前体到产物离子的转变。标准曲线（0.40 - 500 ng/mL）呈线性，定量下限为0.40 ng/mL。根据生物分析方法验证指南（US FDA和欧洲药品管理局），所有验证结果均在可接受范围内。据我们所知，这是首个经过全面验证的测定人血浆中维拉唑酮的方法，并成功应用于大鼠口服药代动力学研究。
