Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Analyst. 2013 Nov 12;138(24):7369-75. doi: 10.1039/c3an01244a.
In human plasma, the total concentration of non-protein binding (NPB) drugs is equal to the free drug concentration because NPB drugs do not or hardly bind to plasma proteins. Thus, centrifuge ultrafiltration (CF-UF) has been used in the determination of the concentration of NPB drugs in human plasma. However, with only a common centrifugation, the recovery and the reproducibility were not as excellent as expected. In addition, we discovered that the values of the volume ratio of ultrafiltrate to sample solution (Vu/Vs) were different and could not be well controlled, which may affect the determination of the drug concentration. The problem also affected the determination of other NBP drugs. In the present work, we used biapenem as a representative drug to study the effect of Vu/Vs on the analysis of NPB drugs concentration in human plasma. The results showed that a Vu/Vs value of less than 0.4 had no effect on the analysis of free drug concentration, while a Vu/Vs value of more than 0.4 was associated with increased recovery rate and overestimation of drug concentration. Therefore, to maintain a Vu/Vs value of less than 0.4 and even at a constant value is the key to accurately determine the concentration of NPB drugs in plasma. Fortunately, with an HFCF-UF device, the Vu/Vs could be well controlled and kept at 0.08 in this study. The recovery rates were almost 100% and the analysis precision was greatly improved. In pharmacokinetics studies, this method was successfully employed to determine the concentration of biapenem with excellent accuracy and reproducibility. HFCF-UF may become a feasible platform for the determination of NPB drugs.
在人血浆中，非蛋白结合（NPB）药物的总浓度等于游离药物浓度，因为 NPB 药物几乎不与血浆蛋白结合。因此，离心超滤（CF-UF）已被用于测定人血浆中 NPB 药物的浓度。然而，仅通过普通离心，回收率和重现性并不如预期的那样出色。此外，我们发现超滤物与样品溶液体积比（Vu/Vs）的值不同，且无法得到很好的控制，这可能会影响药物浓度的测定。这个问题也影响了其他 NBP 药物的测定。在本工作中，我们使用比阿培南作为代表性药物来研究 Vu/Vs 对人血浆中非蛋白结合药物浓度分析的影响。结果表明，Vu/Vs 值小于 0.4 对游离药物浓度的分析没有影响，而 Vu/Vs 值大于 0.4 与回收率的增加和药物浓度的高估有关。因此，保持 Vu/Vs 值小于 0.4 甚至保持恒定值是准确测定血浆中非蛋白结合药物浓度的关键。幸运的是，使用 HFCF-UF 装置，本研究可以很好地控制 Vu/Vs 值，并使其保持在 0.08。回收率几乎达到 100%，分析精度大大提高。在药代动力学研究中，该方法成功地用于测定比阿培南的浓度，具有良好的准确性和重现性。HFCF-UF 可能成为测定 NPB 药物的一种可行平台。
