A single-tube radioimmunoassay for the antiviral agent 2,6-diamino-9-(2-hydroxyethoxymethyl)purine (A134U).

A direct radioimmunoassay for the detection of A134U in biological fluids and extracts has been developed. The entire assay, including scintillation counting, is performed using 12 X 55-mm centrifuge tubes and results in a sensitive, reliable, and relatively inexpensive procedure. The log-logit transformation is linear over a range of 1 to 30 pmol per sample. Intra-assay precision was found to be excellent with a coefficient of variation ranging from 4.1 to 14.5% for the standard curve with plasma and a coefficient of variation ranging from 4.0 to 17.8% for the standard curve with urine. Interassay precision and accuracy were also found to be good. With the antisera chosen for use, no cross-reactivity was found with acyclovir or its two known metabolites, while some cross-reactivity was seen with the corresponding two derivatives of A134U. Only very minor cross-reactivities were seen with a small number of other compounds out of a large number tested.

A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity relationships.

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.

Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (mu) receptors?

Morphine has been found in cow and human milk at concentrations of 200 to 500 nanograms per liter. Multistep purification yields a material that has immunological, biological, pharmacological, and chemical properties identical to those of morphine. Similar morphine-like material, which has been tentatively identified in some common plant sources, may be a ubiquitous dietary constituent and a possible source for the material in milk. Since morphine (mu) receptors have a low affinity for enkephalins, and since morphine-like materials have been described in brain and intestine, it is possible that morphine in food may be the source of this material and a normal ligand specific for mu receptors.