Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei Province 050017, China.
Eur J Pharm Sci. 2013 Jan 23;48(1-2):332-8. doi: 10.1016/j.ejps.2012.11.006. Epub 2012 Nov 28.
Traditional ultrafiltration (UF) usually has a large volume ratio of ultrafiltrate to sample solution, and this ratio cannot be well controlled. It can break the balance of protein-binding equilibrium and exert an influence on the analysis of free drug. In the present study, we evaluated the influence of volume ratio of ultrafiltrate to sample solution on the analysis of free drug in human plasma. We used carbamazepine as a model drug and studied the effect of different centrifugation times on ultrafitrate volume and the related effects on unbound carbamazepine measurement. Moreover, we compared the hollow fiber centrifugal ultrafiltration (HFCF-UF) with traditional UF. Our results showed that the ultrafiltrate volume was changed from 40 to 400 μL with the increase of centrifugation time for the traditional UF, and the related changes in unbound concentration were significant. The rate of protein binding (BP) was changed from 40% to 70%. In contrast, a tiny and invariant ultrafiltrate yield (40 μL) was obtained using the HFCF-UF method, and the BP rate was around 72%. In addition, with the HFCF-UF method, the volume ratio of ultrafiltrate to sample solution could be also well controlled by the inner diameters of both the glass tube and hollow fiber. The HFCF-UF method was a more accurate plasma pretreatment procedure, by which the in vivo balance of protein-binding equilibrium was hardly broken. Therefore, this method was successfully employed to quantify the free fraction of carbamazepine in clinical samples.
传统超滤（UF）通常具有较大的超滤液与样品溶液的体积比，且该比例无法得到很好的控制。这可能会打破蛋白结合平衡，并对游离药物的分析产生影响。在本研究中，我们评估了超滤液与样品溶液体积比对人血浆中游离药物分析的影响。我们以卡马西平为模型药物，研究了不同离心时间对超滤液体积的影响，以及对游离卡马西平测量的相关影响。此外，我们还比较了中空纤维离心超滤（HFCF-UF）与传统 UF。结果表明，传统 UF 的超滤液体积随离心时间从 40μL 增加到 400μL，游离浓度的相关变化具有显著意义。蛋白结合率（BP）从 40%变化到 70%。相比之下，使用 HFCF-UF 方法可获得微小且不变的超滤液产量（40μL），BP 率约为 72%。此外，使用 HFCF-UF 方法，还可以通过玻璃管和中空纤维的内径来很好地控制超滤液与样品溶液的体积比。HFCF-UF 方法是一种更精确的血浆预处理方法，几乎不会打破体内蛋白结合平衡。因此，该方法成功用于定量临床样本中卡马西平的游离分数。
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