Characterization of inactive components in conjugated equine estrogens

Abstract

Objective: Premarin®, Conjugated Estrogens, United States Pharmacopeia (USP), is a pharmaceutical preparation that has been marketed since the 1940s. The conjugated estrogens found in Premarin® are derived from the urine of pregnant mares. The composition of equine-based estrogens has never been fully evaluated or characterized. Design: A complete estrogenic analysis has been undertaken to characterize the essential active components of conjugated equine estrogens (CEE) through the use of chemical analysis, chromatographic analysis, quantitation, and structure-function relationship analysis. Materials/Methods: The characterization was performed on several lots of Premarin® representing a spectrum of age, source and dosage forms (oral and injectable). The characterization process divided the multitudes of unique components into several classes: actives, concomitants, impurities, inconsistent components and insignificant components. Results: The comprehensive characterization provides sufficient scientific evidence that Premarin® contains ten essential active estrogenic components. The batches examined also contain numerous impurities, several of which are common urinary compounds. Many compounds are inconsistent components across batches and insignificant components that provide no proven pharmacological (estrogenic) activity for the treatment of conditions associated with menopause, including vasomotor symptoms. Conclusions: The comprehensive characterization provides sufficient scientific evidence that Premarin® contains high levels of several inactive components. Some of these impurities represent normal compounds usually found in the urine of horses. Supported by: Endeavor Pharmaceuticals, Inc., Wilmington, NC, USA.