Dissolution profiles and specifications for dihydroergotoxine sublingual tablets using a new in vitro method.

A dissolution method (paddle method) for determining the dissolution rate profile for 0.5- and 1.0-mg dihydroergotoxine methanesulfonate sublingual tablets was developed. A fluorometric method was used for measuring drug concentration in the dissolution medium, distilled water. It was essential to filter the dissolution sample to avoid interference from undissolved excipients. When different kinds of filters were used with the dissolution samples and standards, different degrees of apparent drug binding to the filter occurred. The dissolution rate profiles for several different products were compared to the innovator's product. The in vitro method and data obtained were used to propose dissolution specifications for these sublingual products.

Determination of methylergometrine and dihydroergotoxine in biological fluids.

New hapten-carrier conjugates were prepared from 9,10-dihydro-N-[1-(hydroxymethyl)propyl]-6-methylergoline-8-carboxamide 1-hemisuccinate (dihydromethylergometrine hemisuccinate) by coupling with bovine serum albumin employing the mixed anhydride technique. The specificity of anti-dihydromethylergometrine antiserum elicited in the rabbits by immunization with this antigen was tested by cross-reaction studies with methylergometrine, dihydroergotoxine, dihydroergocristine and dihydroergotamine employing [9,10-3H]-dihydromethylergometrine and [9,10-3H]-dihydroergocryptine in the radioimmunoassay procedure. These cross reactivities were observed 100% for methylergometrine, 48.3% for dihydroergotamine, 16.6% for dihydroergotoxine and 6.6% for dihydroergocristine using labeled dihydromethylergometrine. When labeled dihydroergocriptine was the results were 18.3%, 112.1%, 100% and 63.8%, respectively. Methylergometrine concentrations in the postpartal plasma and milk at 2 hr after oral administration of methylergometrine maleate (0.75 mg) to woman were 5.1 ng/ml and 1.3 ng/ml, respectively. Dihydroergotoxine concentrations in the rabbit sera after oral administration of dihydroergotoxine methanesulfonate (4 mg) were studied. The assay was satisfactory to permit the measurement of ergot alkaloid levels in the biological fluids.

Dihydroergotoxine: separation and determination of four components by high-performance liquid chromatography.

The evaluation of a new high-performance liquid chromatographic method is described. It permits the separation and determination of the four components of dihydroergotoxine (dihydroergocristine, dihydroergocornine, dihydro-alpha-ergocryptine, and dihydro-beta-ergocryptine) in a single step. On reversed-phase microparticles, complete baseline separation is possible with different mobile phases containing about 10(-2) M base. The analysis of dihydroergotoxine mesylate drug substance or its dosage forms can be carried out in about 15 min. No reference substance is required for the determination of the proportions of the components. This method is simple and exhibits high accuracy, reproducibility, and selectivity. It permits the analytical control of dosage forms containing dihydroergotoxine mesylate to ensure that they comply with the specifications for the drug substance used in clinical and pharmacological studies.

Determination of dihydroergotoxine alkaloids by gas-liquid chromatography.

A gas-liquid chromatographic (GLC) method has been developed for the separation and determination of dihydroergotoxine alkaloids (dihydroergocristine, dihydroergokryptine and dihydroergocornine), involving quantitative decomposition of the compounds catalysed by a metal surface. GLC was carried out with 2% Dexsil 300 on Gas-Chrom Q as stationary phase, with temperature programming. For the quantitation, phenylbutazone was used as the internal standard.