Separation and characterization of the metabolic products of lappaconitine in rat urine by high-performance liquid chromatography.

The separation and characterization of the metabolic products of lappaconitine in rat urine by high-performance liquid chromatography with electrochemical and ultraviolet detection are described. Urine samples from rats intravenously administered lappaconitine hydrobromide were extracted with chloroform and then purified on a Sep-Pak C18 cartridge. The subsequent resolution into individual compounds was achieved by high-performance liquid chromatography. Identification of these compounds was based on comparisons of the chromatographic behaviour and the detector response with those of authentic samples. Changes in the ratio of lappaconitine to its metabolites in rat urine with time after dosing led to a proposal for one of the probable metabolic pathways of lappaconitine in the rat.

Studies on the metabolism of lappaconitine in humans. Identification of the metabolites of lappaconitine in human urine by high performance liquid chromatography.

The metabolites of lappaconitine in the urine of humans having been previously administered intramuscularly with lappaconitine hydrobromide were studied using high performance liquid chromatography with electrochemical and ultraviolet detection. The urine was extracted by means of liquid- and solid-phase extractions. Each of the metabolites of lappaconitine was purified by high performance liquid chromatography on a reversed phase column and identified on the basis of the chromatographic behaviour and the detector response. It was proved that lappaconitine, N-deacetyl-16-O-demethyllappaconitine and N-deacetyllappaconitine were excreted in urine from humans receiving lappaconitine.

Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines).

Many N1-acyloxymethyl derivatives VI of bis(2,6-dioxopiperazine) I, ICRF-154, were prepared and tested for antitumor activity. The treatment of I with formaldehyde gave a crystalline bis(N1-hydroxymethyl) derivative VII, which was acylated under various conditions to give bis(N1-acyloxymethyl) derivatives VI. Antitumor activity of VI against P388 leukemia in mice was studied. Several bis(N1-acyloxymethyl) compounds such as phenylacetyloxymethyl VI-6, methoxycarbonyloxymethyl VI-41, isobutoxycarbonyloxymethyl VI-44, and furancarboxymethyl VI-38 compounds were found to have potent antitumor activities. On the other hand, water-soluble esters having an amine or a carboxylic acid function in their acyl groups showed rather reduced activity. These bis(N1-acyloxymethyl) derivatives VI were presumably hydrolyzed into the parent bis(2,6-dioxopiperazine) I by nonspecific esterase in the body to exhibit their antitumor activity.

[Assessment of absorption and distribution of artemether in rats using a thin layer chromatography scanning technique].

TLC scanning technique was found to have good specificity for studying the absorption and distribution of artemether in rats. Plasma or tissue homogenates 0.2-1.0 ml were placed in glass extraction tubes and water was added to make 1.0 ml. Each sample was extracted 3 times with 4 ml mixed organic solvent (n-pentane: dichloromethane = 1:1, vol:vol). The organic layers of 3 extractions were combined and evaporated. The residue was dissolved in 100-300 microliters of ethylacetate and spotted on TLC plates. The chromatogram was developed in solvent system consisting of petroleum ether: chloroform: ethylacetate (4:2:1). The color developing agent was 0.25 g p-dimethylaminobenzaldehyde dissolved in a mixture of 2.25 ml 85% phosphoric acid, 47.6 ml of acetic acid and 20 ml of water. Artemether fat emulsion was given intravenously at the dosage of 80 mg/kg. Groups of 5 rats were killed at 15, 30, 60 and 120 min after iv. The results showed that the peak tissue levels were obtained within 15 min, the drug disappeared from the blood very rapidly, and only 0.34 microgram/ml was found in the plasma after 120 min. The highest level was found in brain which attained about 13.9 micrograms/g wet tissue 15 min after iv injection, moderate in heart, lung and skeletal muscle, whereas the levels in liver and kidney were low. At 15, 30 and 60 min, the plasma drug concentrations were 18.5, 6.9 and 2.3 micrograms/ml, and the brain drug concentrations were 14.0, 8.8 and 3.4 micrograms/g wet tissue, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)