Nilsson L B, Schmidt S
DMPK and Bioanalytical Chemistry Development, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden.
J Pharm Biomed Anal. 2001 Mar;24(5-6):921-7. doi: 10.1016/s0731-7085(00)00560-4.
Batch-wise pH-adjustment of plasma samples for free concentration determinations can be performed directly in the ultrafiltration devices using a CO(2) incubator. The pH of the samples could be adjusted to within a sufficiently narrow interval though the initial differences in pH were large. The possibilities for simultaneous determination of free and total concentrations were studied using NAD-299 as a model compound. By adding a known concentration of a (13)C-labelled isotope of the studied drug to the sample prior to ultrafiltration it was possible to calculate the total concentration from the ratio of the drug peak area to the isotope peak area while the free concentration was calculated from the drug peak area. Initial experiments showed good precision and accuracy as well as a good correlation with concentration data acquired in the conventional way.
用于游离浓度测定的血浆样品分批pH调节可直接在超滤装置中使用二氧化碳培养箱进行。尽管样品的初始pH差异很大，但仍可将其调节到足够窄的区间内。使用NAD - 299作为模型化合物研究了同时测定游离浓度和总浓度的可能性。在超滤前向样品中加入已知浓度的所研究药物的（13）C标记同位素，通过药物峰面积与同位素峰面积的比值计算总浓度，而游离浓度则通过药物峰面积计算。初步实验显示出良好的精密度和准确度，并且与以传统方式获得的浓度数据具有良好的相关性。
