Properties, stability, assay, and preliminary pharmacokinetics of the immunomodulatory 1,2-O-isopropylidene-3-O-3'(N',N'-dimethylamino-n-propyl)-D-glucofuranose hydrochloride

Article abstract of DOI:10.1002/jps.2600710404

1,2-O-Isopropylidene-3-O-3(N',N'-dimethylamino-n-propyl)-D-glucufuranose hydrochloride (I) is a new agent with claimed immunomodulatory action and antiviral activity. Thin-layer chromatographic procedures and identifying tests were developed to separate the drug, its synthetic precursors, and solvolytic products, and were applied to stability studies. It is stable in 0.1N NaOH at 60° where its acid solvolysis product, 3-O-3'-(N',N'-dimethylamino-n-propyl)-D-glucose is readily degraded. The partition coefficient of I (pK'(a)=9.28) between chloroform and plasma was 6.4 ± 0.2 SEM between pH 10.5 and 11.0. Plasma and urine (0.5ml) adjusted to pH 11.0 were extracted with 10 ml of chloroform and the extract evaporated. The reconstituted residue in 50 μl of benzene, with the diiopropylaminoethyl analog of I as an internal standard, was derivatized with 50 μl of heptafluorobutyric anhydride at 60° for 45 min and was evaporated and reconstituted in 100 μl of benzene to be assayed for I by GLC with electron capture detection with a sensitivity of 5 ng/0.5 ml of biological fluid. The procedure was applied to pharmacokinetics in the dog and a two-compartment body model was observed with a terminal half-life of 103-130 min. At the 40mg dose, 60-40% was excreted renally unchanged and 20-34% as unidentified metabolites. At the 200-mg dose 82-85% was excreted renally unchanged and 15-17% as unidentified metabolites. The respective renal clerances of I were 135 and 163 ml/min. The respective total clearances of I were 204 and 191 ml/min. These metabolites were apparently unextracted with chloroform from biological fluids at pH 11 and the liquid scintillation counting (LSC) assay of extracted radiolabeled I appeared synonomous with the GLC assay of I in such fluids.