Saini Neeraj Kumar, Sulochana Suresh P, Kiran Vinay, Zainuddin Mohd, Mullangi Ramesh
Drug Metabolism and Pharmacokinetics, Jubilant Biosys, 2nd Stage, Industrial Suburb, Bangalore, India.
Biomed Chromatogr. 2018 Nov;32(11):e4344. doi: 10.1002/bmc.4344. Epub 2018 Aug 13.
A simple, sensitive and rapid assay method has been developed and validated for the estimation of apalutamide on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The method utilizes liquid extraction of apalutamide from 3 mm punched disks from DBS cards (spiked or study samples). The extracted sample was chromatographed on an Atlantis dC column using gradient elution with 0.2% formic acid and acetonitrile at a flow rate of 1.00 mL/min. The total run time was 3.0 min. The MS/MS ion transitions monitored were m/z 478 → 450 for apalutamide and m/z 481 → 453 for the IS (apalutamide-d ). Method validation was performed as per regulatory guidelines. The assay was linear in the range of 0.95-2030 ng/mL. The intra- and inter-day precisions were in the ranges of 2.37-8.53 and 6.76-11.5%, respectively. Stability studies showed that apalutamide was stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of apalutamide obtained from a pharmacokinetic study in mice.
已开发并验证了一种简单、灵敏且快速的检测方法，用于使用液相色谱-串联质谱联用（电喷雾电离正离子模式）测定小鼠干血斑（DBS）中的阿帕鲁胺。该方法利用从DBS卡（加标或研究样本）上3毫米打孔圆片中提取阿帕鲁胺。提取的样品在Atlantis dC柱上进行色谱分析，使用含0.2%甲酸和乙腈的梯度洗脱，流速为1.00毫升/分钟。总运行时间为3.0分钟。监测的MS/MS离子跃迁为阿帕鲁胺的m/z 478→450和内标（阿帕鲁胺-d）的m/z 481→453。按照监管指南进行方法验证。该检测方法在0.95 - 2030纳克/毫升范围内呈线性。日内和日间精密度分别在2.37 - 8.53%和6.76 - 11.5%范围内。稳定性研究表明，阿帕鲁胺在DBS卡上稳定一个月。这种新方法已应用于分析从小鼠药代动力学研究中获得的阿帕鲁胺DBS样本。
