pH-metric log P. 6. Effects of sodium, potassium, and N-CH3-D-glucamine on the octanol-water partitioning of prostaglandins E1 and E2

Abstract

The pH-dependent octanol-water partition behavior of prostaglandins (Pg) E1 and E2 was studied by an automated potentiometric titration method. In 0.15 M KCl at 25 degrees C, the log P values of PgE1 and PgE2 are 3.20 +/- 0.02 and 2.90 +/- 0.02, respectively. The partition parameter also was determined in 0.15 M NaCl, 0.10 M NaCl, and 0.0003 M KCl for PgE1; no ionic strength dependence was observed. In contrast, the Pg anion partitioning, described by the extraction constant, log Ke (= [X+Pg-]OCT/[X+]AQ[Pg-]AQ, where X = Na or K), showed dependence on the nature and concentration of the background salt. For PgE1, the log Ke values are 0.50 +/- 0.08 (0.15 M KCl), 0.18 +/- 0.16 (0.15 M NaCl), 0.86 +/- 0.08 (0.10 M NaCl), and 1.80 +/- 0.09 (0.0003 M KCl); for PgE2, the log Ke value is 0.20 +/- 0.29. The extraction of the Pg anion into octanol by N-methyl-D-glucamine (glucamine) was also studied. In 0.15 M KCl, the log Ke value is 1.82 +/- 0.07. The extraction of the prostaglandin-glucamine complex into octanol maximizes at about pH 8.8. Due to the low aqueous solubility of the prostaglandins, the aqueous pKa values were determined by extrapolation from methanol-water solutions by the Yasuda-Shedlovsky technique. The Debye-Hückel theory was applied to predict the ionic strength dependence of the octanol-water ion-pair extraction constants (log Ke).