Zheng Naiyu, Yuan Long, Ji Qin C, Mangus Heidi, Song Yan, Frost Charles, Zeng Jianing, Aubry Anne-Françoise, Arnold Mark E
Analytical & Bioanalytical Development, Bristol-Myers Squibb Company, Princeton, NJ 08543, United States.
Analytical & Bioanalytical Development, Bristol-Myers Squibb Company, Princeton, NJ 08543, United States.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Apr 15;988:66-74. doi: 10.1016/j.jchromb.2015.02.023. Epub 2015 Feb 21.
Apixaban (Eliquis™) was developed by Bristol-Myers Squibb (BMS) and Pfizer to use as an antithrombotic/anticoagulant agent and has been recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A clinical study of apixaban, sponsored by BMS and Pfizer, included a pilot exploratory portion to evaluate the potential for future drug concentration monitoring using dried blood spot (DBS) sample collection. For DBS sample collection, a fixed blood volume was dispensed onto a DBS card by either regular volumetric pipette (venous blood collection) or capillary dispenser (finger prick blood collection). A 96-well semi-automated liquid-liquid extraction sample preparation procedure was developed to provide clean extracts for UHPLC-MS/MS quantitation. Assays using both partial-spot center punch and whole spot punch were developed and validated. The linear dynamic ranges for all the analyses were from 0.5 to 500 ng/mL. The coefficient of determination (r(2)) values was >0.9944 for all the validation runs. For the center punch approach, the intra-assay precision (%CV) was within 4.4% and inter-assay precision was within 2.6%. The assay accuracy, expressed as %Dev., was within ± 5.4% of the nominal concentrations. One accuracy and precision run was performed using the whole spot approach, the intra-assay precision (%CV) was within 7.1% and the accuracy was within ± 8.0% of the nominal concentrations. In contrast to the center punch approach, the whole spot approach eliminated the effect of hematocrit and high lipids on the analysis of apixaban in human DBS when an accurate sample blood volume was collected on DBS cards.
阿哌沙班（艾乐妥™）由百时美施贵宝公司（BMS）和辉瑞公司研发，用作抗血栓/抗凝剂，最近已被批准用于预防非瓣膜性心房颤动患者的中风和全身性栓塞。由BMS和辉瑞公司赞助的一项关于阿哌沙班的临床研究包括一个试点探索部分，以评估使用干血斑（DBS）样本采集进行未来药物浓度监测的潜力。对于DBS样本采集，通过常规容量移液器（静脉血采集）或毛细管分配器（手指刺血采集）将固定体积的血液分配到DBS卡上。开发了一种96孔半自动液液萃取样品制备程序，以提供用于UHPLC-MS/MS定量的干净提取物。开发并验证了使用部分斑点中心打孔和全斑点打孔的测定方法。所有分析的线性动态范围为0.5至500 ng/mL。所有验证运行的决定系数（r²）值均>0.9944。对于中心打孔方法，批内精密度（%CV）在4.4%以内，批间精密度在2.6%以内。以%Dev.表示的测定准确度在标称浓度的±5.4%以内。使用全斑点方法进行了一次准确度和精密度运行，批内精密度（%CV）在7.1%以内，准确度在标称浓度的±8.0%以内。与中心打孔方法相比，当在DBS卡上采集准确的样本血量时，全斑点方法消除了血细胞比容和高血脂对人DBS中阿哌沙班分析的影响。
