pH lability in serum during equilibrium dialysis.

Abstract

Changes in pH were determined in previously frozen normal human serum during dialysis against sodium phosphate, Krebs Ringer phosphate or Krebs Ringer bicarbonate buffers of pH 7.4. Serum was either untreated (native) or adjusted to pH 7.4 before dialysis. pH in native serum was 7.7-7.9 before dialysis, showed a decrease after 1 h, and an increase after 3 h. pH-adjusted serum showed a continuous pH increase during dialysis. The increase in serum pH during dialysis was larger at 370 C than at 220 C, larger at low than at high buffer molarity, and larger in native than in pH-adjusted serum. The observed changes in serum pH during dialysis are associated with unacceptably large errors in unbound fraction in serum for a number of important drugs. Drug binding determination in serum by equilibrium dialysis should be performed with buffers providing appropriate and stable pH level.

Differences in the serum binding determinants of isradipine and darodipine‐consequences for serum protein binding in various diseases.

“…related to dihydropyridines (Hof et al, 1982, The purpose of this study was Daltons). Previous studies showed that equilibrium with respect to the free drug fraction was achieved within 2 h. As observed previously the pH of frozen serum samples was approximately 8 (Br0rs & Jacobsen, 1985). Preliminary studies showed that dialysing the serum against buffer at pH 7.1 maintained a physiological pH in the system (7.35 < pH < 7.40).…”

A comparison of drug protein binding and alpha 1‐acid glycoprotein concentration in Chinese and Caucasians.

“…Plasma was separated by the membrane from a similar volume of Na2HPO4/KH2PO4 buffer, pH 7.45 containing drug (> 98% radiochemically pure). pH stability was achieved as previously described (Br0rs & Jacobsen, 1985).14 C_ radiolabelled drug (Amersham) was added to produce a concentration of 0.9 ,ug ml-' for lignocaine and 2 ,ug ml-' for warfarin. After equilibration for 4 h 500 plI aliquots were taken from both chambers and radioactivity was determined in a liquid scintillation counter.…”

Blood distribution of levocetirizine, a new non‐sedating histamine H1‐receptor antagonist, in humans

“…As previously observed, the pH of frozen plasma samples was approximately 8 [10]. Concentrated lactic acid was then added to the thawed plasma to adjust the pH to 7.35–7.40.…”