Physical Chemistry of Ergot Alkaloids and Derivatives I: Ionization Constants of Several Medicinally Active Bases

doi:10.1002/jps.2600590526

Journal of Pharmaceutical Sciences

Volume 59, Issue 5, May 1970, Pages 700-701

https://doi.org/10.1002/jps.2600590526 Get rights and content

Abstract

A novel procedure is presented for determination of the ionization constants of several pharmacologically active naturally occurring ergot alkaloids and their congeners. For this purpose use was made of the complexation and consequent solubilization of these poorly soluble molecules by certain xanthines with special emphasis on 7-β-hydroxypropyltheophylline. This method allows an approach to investigation of the approximate pKa values of the proteinaceous alkaloids such as ergotamine which resisted the usual means available for measurement of dissociation constants. It is also illustrative of the weak attractive forces present in complexes of this nature.

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Determination of ergot alkaloids in plasma by high-performance liquid chromatography and fluorescence detection
1981, Journal of Chromatography B: Biomedical Sciences and Applications
Liquid chromatographic methods for the determination of ergotamine and methylergometrine in plasma have been developed. The samples are extracted with an organic solvent at pH 9.0, cleaned by extractions and finally injected on an ODS-Hypersil reversed-phase column with acetonitrile—ammonium carbonate buffer as the mobile phase. The polarity of solvents used for extraction and the mobile phase are varied with the compounds of interest. Ergocristine is used as internal standard for ergotamine, and methysergide for the determination of methylergometrine. The stability of samples and standard solutions for calibration are discussed. Conditions for high selectivity and sensitivity of detection are given. Concentrations down to 100 pg/ml of plasma can be detected with a 3-ml sample.
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The effect of caffeine on the absorption of ergotamine from the rat small intestine was studied. The results of a series of experiments showed that caffeine significantly enhanced absorption of ergotamine from solutions of pH 5.0 when both substances were in solution and when an intact blood supply was either absent (in vitro everted sac experiments) or present (in situ experiments). Caffeine did not appear to influence the absorption rate of ergotamine in in situ experiments when the solution pH was 3.0. Isosorbide dinitrate, a vasodilator, enhanced ergotamine absorption when both substances were administered simultaneously into intestinal loops in situ. Isosorbide dinitrate probably exerts its effect by increasing blood flow to the intestine. The results are consistent with an hypothesis that the rate-determining step in ergotamine absorption is the transport of the drug from a lipid phase (GI membrane) into an aqueous phase (blood). Caffeine is thought to exert its rate-accelerating effect by increasing the water solubility of ergotamine neutral molecules.
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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-α-ergocryptine, and dihydro-β-ergocryp-tine) 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.

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NOTESPhysical Chemistry of Ergot Alkaloids and Derivatives I: Ionization Constants of Several Medicinally Active Bases

Abstract

J. Pharm. Sci.

J. Pharm. Sci.

NOTES
Physical Chemistry of Ergot Alkaloids and Derivatives I: Ionization Constants of Several Medicinally Active Bases