Brent D A, Sabatka J J, Minick D J, Henry D W
J Med Chem. 1983 Jul;26(7):1014-20. doi: 10.1021/jm00361a014.
A highly deactivated octadecyl-bonded silica column and a mobile phase consisting of an water-methanol mixture in the range of blood pH and ionic strength are used to correlate log kappa' with biological activity for a series of sulfonamides and barbiturates. The results were compared to literature methods by using retention volume (VR) and retention indexes (I). For the nine sulfonamides tested, log VR and log kappa' were used with and without correction for ionization. For each biological end point (protein binding and minimum inhibitor concentration against Eschericia coli from two sources) and each independent variable (log kappa' and log VR) the residual standard derivation for the regression was determined. the standard derivations were compared in an F test for each of 12 relevant regressions. Log kappa' was statistically superior in for cases, while log VR was superior in one case. Overall, the methods were statistically indistinguishable. Log kappa' values and I values for 15 barbiturates were regressed against three biological end points [hypnotic activity (the minimum effective dose in rabbits), inhibition of Arbacia egg cell division, and inhibition of rat brain respiration]. Standard deviations were compared by an F test, and the two methods were indistinguishable as far as the goodness of biological correlations are concerned. Procedures for controlling the column's activity are presented. Choices for an appropriate mobile phase are discussed, and a method of calculating pH and ionic strength in a methanol-aqueous mobile phase is presented.
使用高度失活的十八烷基键合硅胶柱和由血液pH值和离子强度范围内的水 - 甲醇混合物组成的流动相，来关联一系列磺胺类药物和巴比妥类药物的log kappa'与生物活性。通过使用保留体积（VR）和保留指数（I），将结果与文献方法进行比较。对于所测试的九种磺胺类药物，使用log VR和log kappa'，且进行了和未进行电离校正。对于每个生物学终点（来自两个来源的蛋白质结合和对大肠杆菌的最小抑菌浓度）和每个自变量（log kappa'和log VR），确定回归的残余标准偏差。在F检验中比较了12个相关回归中每个回归的标准偏差。在某些情况下，log kappa'在统计学上更优，而在一种情况下log VR更优。总体而言，这些方法在统计学上无法区分。针对15种巴比妥类药物的log kappa'值和I值，针对三个生物学终点[催眠活性（兔子的最小有效剂量）、对海胆卵细胞分裂的抑制以及对大鼠脑呼吸的抑制]进行回归分析。通过F检验比较标准偏差，就生物学相关性的优劣而言，这两种方法无法区分。介绍了控制柱活性的程序。讨论了选择合适流动相的方法，并提出了一种计算甲醇 - 水流动相pH值和离子强度的方法。
