Tran Benjamin Duy, Moorthy Ganesh S, Zuppa Athena F
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Center for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Biomed Chromatogr. 2018 Mar;32(3). doi: 10.1002/bmc.4104. Epub 2017 Nov 9.
A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood for up to 120 h at room temperature and 4°C. Whole blood was spiked with K and NK (1000 ng/mL each). Blood samples were aliquoted at different time points (0-120 h), extracted and analyzed using a validated high-performance liquid chromatography tandem mass spectrometry assay. The study demonstrated the stability of both K and NK in whole blood up to 120 h. These in vitro studies suggest that the concentrations of K and NK measured in the PK samples are reliable. The established stability results were successfully employed to investigate K and NK pharmacology studies in critically ill adults.
开展了一项研究，以描述氯胺酮（K）及其代谢产物去甲氯胺酮（NK）在危重症成年患者中的药代动力学（PK）。在这些受试者中进行研究受到在繁忙的重症监护环境中获取的样本需要立即处理和冷冻的阻碍。能够在室温下长时间储存未处理的样本将克服这一障碍。在室温下和4°C条件下，对全血中K和NK的稳定性及血-血浆分配进行了长达120小时的研究。全血中加入K和NK（各1000 ng/mL）。在不同时间点（0至120小时）对血样进行等分，使用经过验证的高效液相色谱串联质谱分析法进行提取和分析。该研究证明K和NK在全血中长达120小时的稳定性。这些体外研究表明，PK样本中测得的K和NK浓度是可靠的。已确定的稳定性结果成功用于研究危重症成年患者的K和NK药理学研究。
