A mass balance approach for calculation of recovery and binding enables the use of ultrafiltration as a rapid method for measurement of plasma protein binding for even highly lipophilic compounds.
A mass balance approach for calculation of recovery and binding enables the use of ultrafiltration as a rapid method for measurement of plasma protein binding for even highly lipophilic compounds.
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DOI：
10.1016/j.jpba.2012.11.018
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发表时间：
2013-03-05
影响因子：
3.4
通讯作者：
Williams, Noelle S.
中科院分区：
文献类型：
--
作者：
Wang, Changguang;Williams, Noelle S.
关键词：
本研究的目的是进一步验证超滤（UF）作为测定血浆蛋白结合（PPB）的方法，通过证明非特异性结合（NSB）不是一个限制，即使是高度亲脂化合物，因为仪器上的NSB位点在血浆存在下被钝化。利用质量平衡理论计算了20种商业和7种研究用化合物在存在和不存在等离子体的超滤过程中的回收率。PPB也使用这种质量平衡方法进行测量，以与快速平衡透析（RED）测定的PPB进行比较，并在文献中发现。对于高NSB的化合物，仅在PBS中存在和不存在血浆时，UF期间化合物的回收率显着不同。超滤法计算的PPB与文献值或RED计算的结果一致。差异可以解释为pH值的变化，达到平衡的时间不足，或者在RED过程中化合物不稳定，这些问题可以通过超滤来解决。因此，在选择UF作为PPB检测方法时，通过传统的化合物在PBS中孵育来测量的NSB不必是一个问题。更合适的方法是计算通过质量平衡测量的等离子体中装置的化合物回收率，以确定该方法对单个化合物的适用性。超滤的传导速度也避免了其他方法可能发生的pH变化或化合物损失。因此，UF的质量平衡法是快速测定PPB的首选方法。
The aim of this study is to further validate the use of ultrafiltration (UF) as a method for determining plasma protein binding (PPB) by demonstrating that non-specific binding (NSB) is not a limitation, even for highly lipophilic compounds, because NSB sites on the apparatus are passivated in the presence of plasma. Mass balance theory was used to calculate recovery of 20 commercial and seven investigational compounds during ultrafiltration in the presence and absence of plasma. PPB was also measured using this mass balance approach for comparison to PPB determined by rapid equilibrium dialysis (RED) and as found in the literature. Compound recovery during UF was dramatically different in the presence and absence of plasma for compounds with high NSB in PBS only. A comparison of PPB calculated by ultrafiltration with literature values or calculated by RED gave concordant results. Discrepancies could be explained by changes in pH, insufficient time to equilibrium, or compound instability during RED, problems which were circumvented by ultrafiltration. Therefore, NSB, as measured by the traditional incubation of compound in PBS, need not be an issue when choosing UF as a PPB assay method. It is more appropriate to calculate compound recovery from the device in plasma as measured by mass balance to determine the suitability of the method for an individual compound. The speed with which UF can be conducted additionally avoids changes in pH or compound loss that can occur with other methods. The mass balance approach to UF is thus a preferred method for rapid determination of PPB.
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影响因子：
15
作者：
MacMillan KS;Naidoo J;Liang J;Melito L;Williams NS;Morlock L;Huntington PJ;Estill SJ;Longgood J;Becker GL;McKnight SL;Pieper AA;De Brabander JK;Ready JM
通讯作者：
Ready JM
影响因子：
2.7
作者：
Lu J;Ma Z;Hsieh JC;Fan CW;Chen B;Longgood JC;Williams NS;Amatruda JF;Lum L;Chen C
通讯作者：
Chen C
影响因子：
4.9
作者：
Kochansky, Christopher J.;McMasters, Daniel R.;Korzekwa, Kenneth R.
通讯作者：
Korzekwa, Kenneth R.
影响因子：
2.2
作者：
MILLIGAN, TP;MORRIS, HC;PRICE, CP
通讯作者：
PRICE, CP
DOI：
10.1007/s10856-010-4169-3
发表时间：
2011-01-01
影响因子：
3.7
作者：
Thakurta, Sanjukta Guha;Subramanian, Anuradha
通讯作者：
Subramanian, Anuradha