Translational Pharmacology Research Core, Center for Integrated Global Biomedical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
Translational Pharmacology Research Core, Center for Integrated Global Biomedical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
J Pharm Biomed Anal. 2018 Jul 15;156:163-169. doi: 10.1016/j.jpba.2018.04.035. Epub 2018 Apr 23.
A liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of tenofovir and tenofovir alafenamide concentrations in human plasma and cerebrospinal fluid. Tenofovir and tenofovir alafenamide were extracted from matrix by solid phase extraction. The dried extraction eluents were dissolved in water for LC-MS/MS analysis. Separation was achieved with a Phenomenex Synergi 4 μm Polar-RP 80A column (50 × 2 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 5 min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 500 ng/mL for the plasma assay and 0.1-50 ng/mL for the cerebrospinal fluid assay. The intra- and inter-day accuracy and precision were less than 12% in low, medium, and high quality control samples for both matrices. The validated methods were applied to the analysis of plasma and cerebrospinal fluid samples of a patient undergoing tenofovir therapy which involved the switch from Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg).
建立并验证了一种三重四极杆液质联用方法，用于测定人血浆和脑脊液中替诺福韦和替诺福韦艾拉酚胺的浓度。替诺福韦和替诺福韦艾拉酚胺通过固相萃取从基质中提取。干燥的萃取洗脱液在水中溶解，用于 LC-MS/MS 分析。分离采用 Phenomenex Synergi 4μm Polar-RP 80A 柱（50×2mm），以水和乙腈中的 0.1%甲酸为流动相进行梯度洗脱。总运行时间为 5 分钟。分析物的检测采用电喷雾电离（正模式）和三重四极杆选择反应监测。血浆分析的标准曲线浓度范围为 0.5-500ng/mL，脑脊液分析的标准曲线浓度范围为 0.1-50ng/mL。两种基质的低、中、高质量控制样品的日内和日间准确度和精密度均小于 12%。该方法已应用于接受替诺福韦治疗的患者的血浆和脑脊液样品分析，该患者从 Stribild（艾维雷韦 150mg/考比司他 150mg/恩曲他滨 200mg/富马酸替诺福韦二吡呋酯 300mg）转换为 Genvoya（艾维雷韦 150mg/考比司他 150mg/恩曲他滨 200mg/替诺福韦艾拉酚胺 10mg）。
