Spectrotitration of ethane-1-hydroxy-1,1-diphosphonic acid (EHDP(tm)) with thorium diaminocyclohexanetetra-acetate.
An automatic spectrotitration procedure for EHDP has been developed. It is applicable to samples containing 50mug or more of EHDP, with a relative standard deviation of 3% if no interfering materials are present. The sensitivity can be extended down to about 5mug, but titration blanks become significant and the standard deviation increases markedly. Thorium diaminocyclohexanetetra-acetate (Th-DCTA) is used as the titrant, to give a ternary species (Th-DCTA)(2)-EHDP. The end-point in the spectrotitration is due to deprotonation of Xylenol Orange indicator when it is incorporated into a weaker ternary species after all the EHDP has reacted. Salts such as NaCl, NaClO(4), Na(2)SO(4) and NaNO(3) interfere if present at concentrations of 0.1-0.5M. The method is much more sensitive to orthophosphate, but this interference can be averted by isolating the EHDP before titration by selectively adsorbing the phosphonate on calcium hydroxyapatite.
Determination of ethane-1-hydroxy-1, 1-diphosphonic acid (EHDP) in human feces and urine.
Abstract Methods have been developed to analyze for EHDP in human excreta. Using 10 g samples of feces and 500 ml of urine, detection limits are 0.015% and 0.1 ppm EHDP, respectively. The accuracy and precision obtained on standards by both procedures vary with level. Sufficient precision data on feces have been obtained so that standard deviation values were calculated for three separate EHDP concentration ranges; σ = 0.006% for samples containing 0.5% EHDP. Replicates have been run on 10 urine samples containing 5–23 ppm and a standard deviation of 0.7 ppm was obtained. Material balance data obtained on approximately 150 analyses run on the excreta of people who took part in 24 separate EHDP studies are good. The average value for the “percentage of dose” accounted for is 101.7%.
The development of a liquid antihistaminic preparation with sustained release properties.
The relative capacity of several cation exchange resins to adsorb methapyrilene has been determined by an in vitro method. It was demonstrated that methapyrilene adsorbed on sulfonic acid cation exchange resin possessed pharmacological activity approximating that of a solution of methapyrilene hydrochloride as measured by the protection against histamine-induced asthma in the intact guinea pig. It is suggested that the use of ion exchange resins as carriers of drugs in liquid dosage forms may be useful in sustained release preparations.