ABSTRACT
To study the related substances in nicergoline, electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of the related substances. Triple quadrupoles tandem MS/MS was employed for the determination of the fragmentations of the parent ions. 16 related substances were detected and identified to be eight synthetic by-products and eight degradation products, by using impurity references matching, product mass spectra fragmentations elucidation, and verified further according to synthetic processes and stress testing results. The results obtained are valuable for nicergoline manufacturing process control and quality assurance.
Subject(s)
Chromatography, High Pressure Liquid , Nicergoline/chemistry , Tandem Mass Spectrometry , Nicergoline/chemical synthesis , Quality ControlABSTRACT
The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.
Subject(s)
Ergolines/chemical synthesis , Nicergoline/chemical synthesis , Sympatholytics/chemical synthesis , Administration, Oral , Animals , Delayed-Action Preparations , Dihydroergotamine/pharmacology , Guinea Pigs , Injections, Intravenous , Male , Nicergoline/administration & dosage , Nicergoline/analogs & derivatives , Receptors, Adrenergic, alpha/drug effects , Structure-Activity RelationshipABSTRACT
The synthesis and the pharmacological activities of 24 analogues of the alpha-adrenergic blocking drug, nicergoline (I b), are reported. The majority of the new compounds were found to be less active than (I b): the structure-activity relationships are presented and discussed.
