demecolcine and trimethylcolchicinic-acid-methyl-ether

In an effort to characterize the pharmacokinetic behavior of the antimitotic agent N-desacetylcolchicine a selective, sensitive high-performance liquid chromatographic method was developed for the determination of N-desacetylcolchicine, demecolcine and colchicine in serum or urine. To 0.5 ml of serum or 0.1 ml of urine diluted to 0.5 ml were added 50 microliters demecolcine (2 micrograms/ml) which serves as the internal standard. The sample was extracted using a C2 reversed-phase solid extraction column. N-Desacetyl-colchicine, colchicine and the internal standard were eluted from the column with methanol. The combined eluates were evaporated to dryness and the residue was reconstituted with water. The reconstituted sample was injected into a C18 reversed-phase column and eluted using a mobile phase consisting of 0.1 M potassium dihydrogenphosphate, 5 mM 1-pentanesulfonic acid in methanol and acetonitrile with a final pH of 6.0, at a flow rate of 1.5 ml/min. N-Desacetylcolchicine, colchicine and the internal standard were detected using a variable-wavelength ultraviolet detector at 254 nm. The limit of detection was 0.4 ng/ml for desacetylcolchicine and 4.0 ng/ml for colchicine. The method is linear over a concentration range of 1.0-200 ng/ml. The method has been shown to be a rapid, reliable method to monitor N-desacetylcolchicine levels in clinical trials in cancer patients.

Topics: Chromatography, High Pressure Liquid; Colchicine; Demecolcine; Humans; Microchemistry; Molecular Structure; Quality Control

Colchicine and its less toxic derivatives (demecolcine and deacetyl colchicine), in dependence on the concentration in the incubation medium, inhibited the activity of adenosine deaminase in the lymphocytes. All the three substances increased the level of cyclic adenosine monophosphate which has the ability of influencing the proliferation of T-lymphocytes. Colchicine and its derivates also inhibited the activity of purine nucleooxidophosphorylase, which, similarly as adenosine deaminase, is a marker enzyme of T-lymphocytes. The results obtained lead to the assumption that the mentioned preparations inhibit the function of T-lymphocytes.

Topics: Adenosine Deaminase; Colchicine; Cyclic AMP; Demecolcine; Humans; T-Lymphocytes